Prostate Cancer Trials

Asymptomatic men without pain due to prostate cancer progressing with metastatic castrate resistant prostate cancer (mCRPC) after treatment with combination or sequential ADT (androgen deprivation therapy, a type of hormonal therapy) + Abiraterone (Zytiga, a type of hormonal therapy) will be treated on a randomized, open label study to determine if sequential treatment with high dose testosterone (a hormone) and Enzalutamide (Xtandi, a type of hormonal therapy) will improve progression free survival (PFS) versus continuous Enzalutamide alone as standard therapy. This study has 2 arms: Arm A: Enzalutamide alone Patients randomized to Arm A will receive continuous therapy with standard dose Enzalutamide 160 mg taken by mouth (orally or po) daily. Arm B: Testosterone + Enzalutamide Patients randomized to Arm B will receive an intramuscular (IM) injection with testosterone cypionate or testosterone enanthate at a dose of 400 mg every 56 days, followed by Enzalutamide 160 mg taken by mouth daily.

PROMISE aims to create a comprehensive nationwide registry of prostate cancer patients with germline pathogenic variants (targetable mutations) by screening approximately 5,000 subjects with a confirmed prostate cancer diagnosis, either through tissue biopsy, PSA greater than 100 ng/dL and/or radiographic evidence of disease and receiving systemic therapy for prostate cancer. Patients at all stages of disease will be welcome to participate in the PROMISE Registry. Participants will be recruited and screened over a five-year period. Study participants will be asked to provide a saliva sample to be tested for germline cancer risk variants through Color Health. If the results identify a pathogenic or likely pathogenic variant, an appointment with a genetic counselor from Color Health will be scheduled to discuss the results. Participants will complete a baseline demographic survey that includes self-reported health history, family history of cancer and standardized patient reported outcome (PRO) measures. PROMISE Registry staff will request medical records from the participant's cancer care provider(s) for the purpose of obtaining clinical data. Participants will receive bi-annual newsletters offering information on new developments in treatment and research opportunities, including clinical trials, associated with genetic variants. Eligible participants (those with target germline mutations) will be followed every 6 months to obtain updated health records data and patient-reported outcomes data. Participants will be followed for a minimum of 15 years. The PROMISE registry will help identify prostate cancer patients with pathogenic variants to learn more about how these variants affect patient outcomes. Ultimately, we hope to help patients learn more about their disease and the treatments that they may derive the most benefit from, including the germline genetic biomarker-based clinical trials they may be eligible for. There is no treatment given as part of this study – it is a registry only.

This is a Phase 1/2 study of EPI-7386 (a type of hormonal therapy) orally administered in combination with enzalutamide (Xtandi, a type of hormonal therapy) in subjects with metastatic castration-resistant prostate cancer (mCRPC). Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the safety and tolerability of the drug combination and establish the recommended dose for EPI-7386 and enzalutamide when dosed in combination. In addition, blood sampling will be conducted for evaluation to assess the potential interaction between the two drugs. This study has 2 treatment arms: Arm A: EPI-7386 + Enzalutamide EPI-7386 given by mouth (PO, orally) at varying dose levels PLUS Enzalutamide given by mouth at 120 mg or 160 mg. Arm B: Enzalutamide alone Enzalutamide given by mouth at 160 mg.

The study is comparing the effect on weight of providing home-delivered whole-food, plant-based meals versus standard, general nutritional counseling to men with prostate cancer on androgen-deprivation therapy (ADT, hormonal therapy). Prostate cancer is the most common cancer diagnosis for men in the United States. For patients with advanced or recurrent disease, ADT has is the cornerstone of systemic treatment. Overall, almost half of prostate cancer patients will undergo ADT at some point during their treatment. Unfortunately, ADT has metabolic side effects, including weight gain, central adiposity (fat around your middle/stomach area), and insulin resistance. This study is a multi-site randomized phase II trial comparing a home-delivered whole food, plant-based diet (WFPBD) with specialized behavioral coaching to standard dietary intervention with general nutritional counseling to assess the efficacy of a WFPBD in promoting weight loss in overweight/obese men receiving ADT. The home-delivered WFPBD will be for 28 days with 12 meals a week followed by 28 days with 6 meals a week; followed by self-prepared WFPBD for 18 weeks (for a total of 26 weeks). The study hypothesis is that a WFPBD will decrease body weight and decrease systemic metabo-inflammation (inflammation caused by excessive weight) in overweight/obese men (BMI > 27) with prostate cancer receiving ADT. Secondary objectives will be to assess the effects of a WFPBD on adiposity, markers of inflammation, and fecal microbiota (gut or GI tract bacteria) that may contribute to prostate cancer progression; to assess the effects of a WFPBD on quality of life; and to assess the durability of any observed effect of the intervention after cessation of the meal-delivery service. This study has 2 treatment arms: Arm A: Whole-food, Plant-Based Diet Pre-packaged, plant-based meals (prepared by Plantable) will be delivered weekly to participants' homes for 8 weeks. Meals are made with whole ingredients including whole grains, vegetables, legumes, nuts and seeds. Added sugar, animal-based products, refined grains, and processed foods are not used in any meal. Participants will be coached by phone calls, texts, emails, and the app throughout the intervention to prepare meals in accordance with the diet. Participants will have access to a Registered Dietitian. During the first 4 weeks, 12 meals/week will be provided to participants; followed by 6 meals/week for the next 4 weeks; followed by 18 weeks where participants will continue to receive coaching but will be expected to make all their own whole-food, plant-based meals using Plantable's assistance. Arm B: General Nutritional Counseling All study participants will receive consult with a Registered Dietitian at the Baseline visit and visit 1 study assessments. After visit 1, study participants assigned to the general nutritional counseling arm will receive an additional in-person or telehealth consultation with a Registered Dietitian that will consist of identification and counseling to improve diet quality and achieve a healthy body weight consistent with American Cancer Society guidelines. Study participants in the control group will continue to receive general nutritional counseling and education with weekly scheduled telephone consultations with a Registered Dietitian for the first 4 weeks of the study period. For the remainder of the study period, they will receive counseling and education from Registered Dietitians via monthly scheduled phone calls.

This study will attempt to determine the effectiveness of nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) combination therapy followed by nivolumab monotherapy in patients with metastatic prostate cancer harboring a loss of CDK12 function (a specific type of genetic tumor mutation). All patients will begin receiving combination therapy in clinic with nivolumab 3 mg/kg intravenously (IV) and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at a flat dose of 480 mg IV every 4 weeks through the end of the planned study duration, for up to 52 weeks of total therapy.

This is a study of Bipolar Androgen Therapy (BAT, a type of hormonal therapy) plus Radium-223 (RAD, a type of bone targeted therapy) in men with metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC with progressive disease (radiographically and/or biochemically) who have been treated with gonadotropin-releasing hormone (GnRH)-analogue (LHRH agonists/antagonists) continuously or bilateral orchidectomy will be enrolled in this study. Previous antiandrogen therapies are permitted, but no more than one (such as abiraterone, enzalutamide, apalutamide, darolutamide). All patients will receive treatment with Radium-223 at a dose of 55 Kilobecquerel (kBq) per kilogram of body weight intravenously (IV) every 28 days, for 6 cycles, plus Testosterone Cypionate 400mg Intramuscular (IM) every 28 days, until progression or unacceptable toxicity.

Previous studies of high dose testosterone (a type of hormone) therapy given intramuscularly (IM, injection) to men with metastatic castrate resistant prostate cancer suggest that high serum levels of testosterone may be required for clinical response. This trial will analyze the effects of oral testosterone therapy in men with metastatic castrate resistant prostate cancer taken on a schedule of seven days of oral testosterone therapy followed by seven days of no therapy for a twenty-eight day cycle. This therapy will be given for three 28 day cycles consecutively followed by radiographic scans to evaluate the metastatic disease. Patients will be allowed to continue on this therapy until the patients show signs of radiographic progression. If the patients show signs of radiographic progression after the first three cycles, the patients will stop taking the oral testosterone therapy and begin taking enzalutamide (Xtandi, a type of hormonal therapy) therapy. Enzalutamide therapy will be taken for three 28 day cycles, then radiographic scans will be taken. If there are no signs of radiographic progression, patients can continue to take enzalutamide therapy for an additional 3 cycles while on study. Patients with continued PSA or objective response will come off study but continue on enzalutamide as standard of care therapy. This study will help the investigators to understand if treating these men with the highest FDA approved dose of oral testosterone therapy will achieve similar and sustained high levels of serum testosterone that will produce similar or enhanced therapeutic response to the therapy when compared to the serum testosterone levels found in the previous injection therapy trials. This study has 1 treatment arm: Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide Therapy Oral Testosterone Therapy, 396 mg given by mouth (PO, orally) twice per day on days 1-7 and 15-21 of a 28 day cycle until radiographic progression. After a 21 day washout period, Enzalutamide therapy given by mouth at 160 mg once daily will be taken for a maximum of 6 cycles while on study.

Some men who have been treated for localized prostate cancer with surgery or radiation still show signs of the disease in their blood. This is called biochemically recurrent prostate cancer. Radium-223 is a small molecule. It uses radiation to kill cancer cells and improves survival in advanced prostate cancer. Researchers want to see if it can treat prostate cancer and induced immune changes earlier in the disease when the cancer is only detectable by prostate specific antigen (PSA) in the blood. Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer patients with biochemical progression after localized therapy with either definitive radiation or surgery (biochemically recurrent prostate cancer or BRPC). A primary goal in these patients is to prevent morbidity from their cancer that results from disease progression and metastatic disease on conventional imaging. Radium-223 has demonstrated the ability to improve survival in men with symptomatic metastatic castration resistant prostate cancer (mCRPC) with a manageable toxicity profile, particularly in patients who have not yet received docetaxel. Radiation, even at low doses can impact immune recognition and immune cell killing of cancer cells. Recent findings suggest that radium-223 increase the killing of prostate cancer cells. Radium-223 may present an alternative option for patients with BRPC that is not associated with substantial toxicity (as seen with ADT) and may have a lasting effect due to its potential effect on the immune system and/or the bone microenvironment. This study has 1 treatment arm: Treatment: All patients will receive radium-223 treatment once every 4 weeks for up to 6 cycles. 18F-NaF PET scans will be used to assess response in bone.

This trial studies the best dose and side effects of olaparib (a type of targeted therapy) and how well it works with radium Ra 223 dichloride (Xofigo, a type of radiation therapy) in treating patients with castration-resistant prostate cancer that has spread to the bone and other places in the body (metastatic). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radioactive drugs, such as radium Ra 223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Giving olaparib and radium Ra 223 dichloride may help treat patients with castration-resistant prostate cancer. This study has 2 arms: Arm A: radium Ra 223 dichloride plus olaparib Patients receive radium Ra 223 dichloride intravenously (IV) over 1 minute on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive olaparib by mouth (PO) twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm B: radium Ra 223 dichloride alone Patients receive radium Ra 223 dichloride as in Arm A. Patients with radiographic progression may crossover to Arm A. If patients have already completed all 6 infusions of radium, they will receive olaparib alone. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib.

This study uses multiparametric MRI-guided and MR-guided biopsies as tools to evaluate response to local radiation therapy. Study subjects include men who have not received any prior treatment but are about to undergo radiation therapy and men whose cancer is progressing after initial radiation therapy. The goal is to use the imaging studies and the genetic information from the biopsies to draw conclusions on how they relate to the efficacy of radiation and radiation resistance. All participants will receive an initial multiparametric MRI and a tissue biopsy. Men who are scheduled for radiation therapy will undergo that therapy. Six months following completion of radiation, they will complete another MRI and additional blood tests.

Prostate cancer is a common cancer among men. There are several ways to treat it, including hormone blocking drugs, radiation therapy, and surgery. Researchers want to combine abiraterone (a type of hormonal therapy) and enzalutamide (a type of hormonal therapy) to see if there is a better way to treat prostate cancer. They also want to study a new radiotracer called 18F-DCFPyL, with the help of a scan called positron emission tomography/computed tomography (PET/CT) to see if there is a better way to detect prostate cancer. Most men diagnosed with prostate cancer will present with intermediate or high-risk disease, and many develop castrate resistant prostate cancer (CRPC) as curative strategies are often unsuccessful. Treatment options typically involve a radical prostatectomy (RP) or radiation therapy (RT) in combination with androgen deprivation therapy (ADT, hormonal therapy). PET imaging based on prostate specific membrane antigen (PSMA), including use of the radiotracer DCFPyL, which binds PSMA, has emerged as a sensitive modality to detect localized and metastatic prostate cancer. It is unknown how androgen-targeted therapy affects expression of the androgen- regulated PSMA gene, FOLH1, and 18F -DCFPyL-PET/CT sensitivity; and, the correlation between response on 18F -DCFPyL-PET/CT imaging and clinical response needs further evaluation. The use of highly effective androgen pathway inhibitors enzalutamide and abiraterone offers an opportunity to understand the characteristics of 18F -DCFPyL-PET imaging during treatment while potentially improving the cure rate of men with potentially lethal localized prostate cancer. All participants will receive: Drug: Goserelin will be administered by sub-cutaneous injection (SC) at 10.8 mg once every 12 weeks for 6 months Drug: Enzalutamide will be taken orally (PO) at 160mg once daily for 6 months Drug: Abiraterone will be taken orally at 1000 mg once daily for 6 months Drug: Prednisone will be taken orally at 5mg twice a day for each dose, or 10 mg once a day. Scans: scans with 18F-DCFPyL will be performed after 2 and 6 months of treatment Procedure: Prostate tumor biopsy samples for research analyses will be taken at baseline and after 2 month scans are performed Procedure: Radical prostatectomy to be determined with your treating physician

This study will be undertaken to evaluate the feasibility of replacing systemic Androgen Deprivation Therapy (ADT, a type of hormonal therapy) with targeted local delivery of an anti-androgen agent alone in patients in whom ADT + radiation therapy is indicated for the treatment of localized prostate cancer. This study has 1 treatment arm: Biolen (bicalutamide, a type of hormonal therapy) + Radiation Therapy Localized single delivery of the Biolen implant (polymer + bicalutamide) with stereotactic body radiation therapy

This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib (a PARP inhibitor, a type of targeted therapy) and enzalutamide (Xtandi, a type of hormonal therapy) combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has spread to other places in the body (metastatic) and has become resistant to testosterone-deprivation therapy (castration-resistant). Enzalutamide helps fight prostate cancer by blocking the use of testosterone by the tumor cells for growth. PARP inhibitors, such as rucaparib, fight prostate cancer by prevent tumor cells from repairing their DNA. Giving enzalutamide and rucaparib may make patients live longer or prevent their cancer from growing or spreading for a longer time, or both. It may also help doctors learn if a mutation in any of the DNA repair genes is helpful to decide which treatment is best for the patient. This study has 2 arms: Arm A: Enzalutamide plus rucaparib Patients receive enzalutamide by mouth (PO) once daily (QD) and rucaparib PO twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm B: Enzalutamide plus placebo Patients receive enzalutamide PO QD and placebo PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

The purpose of the study is to evaluate the safety and effectiveness of talazoparib (a type of targeted therapy) in combination with enzalutamide (a type of hormonal therapy) compared with placebo in combination with enzalutamide in participants with DDR-deficient (a type of genetic mutation) metastatic castration sensitive prostate cancer (mCSPC). This study has 2 treatment arms: Arm A: Talazoparib plus enzalutamide Talazoparib 0.5 mg by mouth (orally or PO) once daily plus enzalutamide 160 mg by mouth once daily. Arm B: Placebo plus enzalutamide Placebo 0.5 mg by mouth (orally or PO) once daily plus enzalutamide 160 mg by mouth once daily.

Prostate cancer is the second leading cause of cancer-related death in American men. The disease recurs in up to 50,000 men each year after their early-stage disease was treated; however, at this stage, imaging scans are often unable to find the disease in the body. In this natural history study, researchers want to find out if a new radiotracer (18F-DCFPyL) injected before positron emission tomography (PET) imaging can help identify sites in the body with cancer. The objective of this study is to learn more about how 18F-DCFPyL PET/CT scans detect change over time in men with recurrent prostate cancer. There is no treatment given as part of this study. Participants will be screened with blood tests. They will also have a bone scan and a computed tomography (CT) scans of the chest, abdomen, and pelvis. Participants will have an initial study visit. They will have a physical exam and blood tests. They will have a PET/CT scan with 18F-DCFPyL. The radiotracer will be injected into a vein; this will take about 20 seconds. The PET/CT scan will be done 1 to 2 hours later. Participants will lie still on a scanner table while a machine captures images of their body. The scan will take 45 minutes. Participants will return for blood tests every 3 months. Participants will return for additional scans with 18F-DCFPyL on this schedule: Once a year if their previous scan was negative for prostate cancer. Every 6 months if their previous scan was positive for prostate cancer. Participants may be in the study up to 5 years.

Phase II Trial of 18F-DCFPyL Imaging as a Method to Assess Treatment Response to Stereotactic Body Radiation Therapy Identifying medium- and high-risk prostate cancer early may allow for treatments to work. But identification can be hard. Researchers want to see if a radiotracer used during PET scans can help. The purpose of this study is to test how an imaging agent called 18F-DCFPyL detects response to standard prostate cancer treatment. This study has 1 treatment arm: Participants will have baseline MRI and PET/CT scans. For the MRI, they may get a contrast agent by IV (intravenous) injection. For the PET/CT scan, they will get an IV injection of 18FDCFPyL. About 1 to 2 hours later, they will get the PET/CT scan. During the scans, participants will lie on their back and remain still for 45 minutes to 1 hour. These scans will be repeated at different points during the study. Participants will get SBRT (stereotactic body radiation therapy) with or without ADT (androgen deprivation therapy, a type of hormonal therapy). 18F-DCFPyL imaging will be performed at baseline, 8 weeks after ADT initiation, 6 months post SBRT and at recurrence.

This study will assess the effectiveness of single pulsed-dose flutamide (a type of anti-androgen or hormonal therapy) in creating double strand breaks (changes to the prostate cancer tumor cells) in prostate cancer within patients receiving central androgen suppression (hormonal therapy) and brachytherapy (radiation therapy). This study has 2 arms: Arm A Experimental: Flutamide A single dose of flutamide 50mg taken by mouth (orally) once prior to brachytherapy and prostatic biopsy. Arm B: Placebo A single dose of placebo taken by mouth (orally) once prior to brachytherapy and prostatic biopsy.

This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. The addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading. INDUCTION (all participants): Participants receive 1 of 6 acceptable forms of standard systemic therapy (SST) for 22-28 weeks. The decision of which of the 6 possible options (listed here) will be decided with your doctor. 1. Participants undergo a bilateral orchiectomy. 2. Participants receive goserelin acetate (a type of hormonal therapy) subcutaneously (SC) every 28 days or 12 weeks OR, histrelin acetate (another type of hormonal therapy) SC every 12 months OR, leuprolide acetate (another type of hormonal therapy) SC or intramuscularly (IM) every 1, 3, 4, or 6 months OR, triptorelin (another type of hormonal therapy) every 1, 3, or 6 months. 3. Participants receive goserelin acetate SC every 28 days or 12 weeks OR, histrelin acetate SC every 12 months OR, leuprolide acetate SC or IM every 1, 3, 4, or 6 months OR, triptorelin every 1, 3, or 6 months. Participants also receive nilutamide (a type of hormonal therapy) orally (PO) daily OR, flutamide (another type of hormonal therapy) PO every 8 hours OR, bicalutamide (another type of hormonal therapy) PO daily. 4. Participants receive degarelix (a type of hormonal therapy) by injection for 2 doses and then every 28 days. 5. Participants receive nilutamide PO daily OR, flutamide PO every 8 hours, OR bicalutamide PO daily. Participants also receive docetaxel (Taxotere, a type of chemotherapy) intravenously (IV) over 1 hour every 3 weeks with or without prednisone (a type of steroid) PO every 12 hours. 6. Participants receive nilutamide PO daily OR, flutamide PO every 8 hours, OR bicalutamide PO daily. Participants also receive abiraterone (a type of hormonal therapy) PO daily or prednisone PO every 12 hours. After completion of 22-28 weeks of SST, participants are then randomized to 1 of 2 arms: ARM I: Participants receive 1 acceptable form of SST as in Induction (above) except for treatment with docetaxel and prednisone.

The purpose of this study is to evaluate the prevalence of 4 or more DNA-repair defects in a population of men with metastatic Prostate Cancer (PC) and to use the results reported to assess eligibility for niraparib (Zejula, a type of targeted therapy, a PARP inhibitor) treatment studies. Participants will be consented to saliva, blood, or existing tumor tissue sample testing for the presence or absence of DNA repair defects. This is NOT a treatment study.

This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of etrumadenant (AB928, a type of targeted therapy)-based combination therapy in participants with metastatic castrate resistant prostate cancer (mCRPC). This study has multiple arms with 2 standard of care comparator arms: Arm A: Etrumadenant + zimberelimab + enzalutamide Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab (a type of immunotherapy) and standard oral enzalutamide (Xtandi, a type of hormonal therapy). Comparator: Enzalutamide Participants will receive standard of care oral enzalutamide. Arm B: Etrumadenant + zimberelimab + docetaxel Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel (Taxotere, a type of chemotherapy) Comparator: Docetaxel Participants will receive standard of care dose of IV docetaxel. Arm C: Etrumadenant + zimberelimab Oral etrumadenant in combination IV zimberelimab. Arm D: Etrumadenant + zimberelimab + AB680 Participants will receive oral etrumadenant in combination with IV zimberelimab and IV AB680 (a type of targeted therapy). Arm E: Etrumadenant + AB680 Participants will receive oral etrumadenant in combination with IV AB680.

The purpose of this study is to assess the safety, tolerability, and toxicity of docetaxel (Taxotere, a type of chemotherapy) alone, in combination with BMS-986218 (a type of immunotherapy), or in combination with nivolumab (Opdivo, a type of immunotherapy) plus BMS-986218 in men who have metastatic castration-resistant prostate cancer (mCRPC) that progressed after novel antiandrogen therapy and have not received chemotherapy for mCRPC. This study has 4 potential treatment arms: Arm A: Docetaxel alone Docetaxel will be given intravenously (IV) in clinic per standard of care. Arm B: Docetaxel + BMS-986218 Docetaxel will be given intravenously (IV) in clinic per standard of care. BMS-986218 will be given IV in clinic; dosing and schedule to be provided by treatment team. Arm C: Docetaxel + BMS-986218 + Nivolumab Docetaxel will be given intravenously (IV) in clinic per standard of care. BMS-986218 will be given IV in clinic; dosing and schedule to be provided by treatment team. Nivolumab will be given IV in clinic; dosing and schedule to be provided by treatment team. Arm D: BMS-986218 + Nivolumab BMS-986218 will be given IV in clinic; dosing and schedule to be provided by treatment team. Nivolumab will be given IV in clinic; dosing and schedule to be provided by treatment team.

The main purpose of this study to define the good and/or bad effects of the combination of enzalutamide (a type of hormonal or anti-androgen therapy) and CC-115 (a type of targeted therapy) in patients with castration-resistant prostate cancer. The hypothesis that combining CC-115 with enzalutamide will increase anti-tumor activity (patients will have a better treatment response) over enzalutamide given alone.

Dosing will be either:

1. Cohort 1: CC-115 5 mg taken orally (at home) twice a day PLUS enzalutamide 160 mg taken orally (at home) once a day, OR

2. Cohort 2: CC-115 10 mg taken orally (at home) twice a day PLUS enzalutamide 160 mg taken orally (at home) once a day, OR

3. Cohort 3: CC-115 20 mg taken orally (at home) twice a day PLUS enzalutamide 160 mg taken orally (at home) once a day.

This study will assess the effectiveness and safety of capivasertib (a type of targeted therapy) plus abiraterone (Zytiga, a type of hormonal therapy) plus androgen deprivation therapy (ADT) versus placebo plus abiraterone plus ADT in participants with metastatic hormone sensitive prostate cancer (mHSPC) whose tumors are characterized by PTEN deficiency. The intention of the study is to demonstrate that in participants with mHSPC, the combination of capivasertib plus abiraterone plus ADT is superior to placebo plus abiraterone plus ADT in participants with mHSPC characterized by PTEN deficiency. The study has 2 treatment arms: Arm A: Capivasertib + Abiraterone Capivasertib 400 mg (2 tablets) by mouth (orally or PO) twice daily (BID) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops PLUS Abiraterone Acetate administered by mouth (orally or PO) as tablets at a dosage of 1000 mg once daily. Administered continuously until criteria for discontinuation are met. Arm B: Placebo + Abiraterone Placebo will be matched to capivasertib appearance (2 tablets) by mouth (orally or PO) twice daily (BID) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops PLUS Abiraterone Acetate administered by mouth (orally or PO) as tablets at a dosage of 1000 mg once daily. Administered continuously until criteria for discontinuation are met.

This is a Phase II non-blinded randomized study evaluating men with oligometastatic prostate cancer lesions randomized to stereotactic ablative radiation therapy (SABR) versus SBAR + Radium-223 (Xofigo, a type of radioactive injection). We are looking to determine the progression-free survival of men who have oligometastatic prostate cancer with at least one bone metastasis with stereotactic ablative radiation therapy (SABR) versus SABR + Radium-223. The metastatic capacity of prostate cancer (PCa) behaves along a spectrum of disease that contains an oligometastatic state where metastases are limited in number and location. The importance of local consolidation of all tumor deposits in oligometastatic disease to delay further metastatic spread is now backed by small randomized studies. There is important early clinical data suggesting the existence of an oligometastatic state and the importance of local therapies in the management of these patients. Radiopharmaceutical therapy (RPT) approaches have not been applied in the oligometastatic space and thus the opportunity to target micrometastatic (not visible on imaging) disease in conjunction with local consolidation of macroscopic (visible on imaging) disease with SABR has the potential to provide a curative model for patients with oligometastatic PCa. We hypothesize macroscopic prostate tumors support the growth of and help nurture future distant metastases and this process can be impacted most by total, macro- and microscopic, tumor consolidation. In addition, we hypothesize that circulating biomarkers can identify men with oligometastasis that benefit the most from SABR and RPT.

This is a Phase 1, open-label study that will evaluate the safety and tolerability of FT-7051 (a type of targeted therapy) and determine the recommended dose, as well as pharmacokinetics (PK or how your body processes a drug), preliminary anti-tumor activity, and pharmacodynamics (PD or how a drug effects your body) in men with metastatic castration-resistant prostate cancer who have progressed despite prior therapy and had been treated with at least one potent anti-androgen therapy (or hormonal therapy). This study has 1 treatment arm: Dose escalation study of FT-7051: Capsules available in strengths of 10mg, 25mg, and 100 mg that are orally administered per the protocol frequency and dose level, which will be provided by your study team.

This research study is studying a combination of hormonal therapy, chemotherapy, and immunotherapy as a possible treatment for metastatic hormone-sensitive prostate cancer. The names of the study drugs involved in this study are: Androgen deprivation therapy (ADT, hormonal therapy) with a drug of your physician's choice. This may include leuprolide (Lupron), goserelin acetate (Zoladex), or degarelix (Firmagon). Docetaxel (Taxotere, a type of chemotherapy) Nivolumab (Opdivo, a type of immunotherapy). The combination of ADT, also called hormonal therapy, with docetaxel chemotherapy and nivolumab immunotherapy is considered investigational. ADT cuts off the supply of testosterone and is the standard of care for hormone sensitive prostate cancer. The addition of docetaxel chemotherapy has been found to prolong life for prostate cancer patients starting hormonal therapy for the first time for metastatic disease, who also have a large volume of cancer. Another anti-cancer treatment modality is called immunotherapy. The immune system can kill cells that are recognized as different or dangerous, such as infected cells and cancer cells. Nivolumab is an antibody (a type of human protein) that work to stimulate the body's immune system to recognize and fight cancer cells. Hormonal therapy and chemotherapy may make cancer cells more recognizable to the immune system and make cancer cells more susceptible to immunotherapy. The goal of this study is to examine the activity and safety of hormonal therapy combined with docetaxel chemotherapy and nivolumab immunotherapy for hormone sensitive prostate cancer. Treatment – all patients will receive the same treatment of ADT combined with docetaxel chemotherapy and nivolumab immunotherapy. Androgen Deprivation Therapy: Given per standard care for duration of study. Nivolumab: Given once every 3 weeks for cycle 1-6 intravenously (IV) in clinic, and then every 4 weeks during subsequent cycles, at a predetermined dosage. Docetaxel: Given once every 3 weeks intravenously (IV) in clinic at a pre-determined dosage for cycle 1-6.

Research studies have shown that genetic changes and family history may increase a man s risk for prostate cancer. Researchers want to follow the prostate health of men who have specific genetic changes associated with prostate cancer to help them learn more about which men are at higher risk for prostate cancer. Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in American men. Prostate cancer has substantial inherited predisposition and certain genetic variants that are associated with an increased risk of prostate cancer. An evolving approach to prostate cancer screening is to target populations at risk of developing prostate cancer based on their genetic predisposition. The objective of this study is to study men with specific genetic changes and determine who is at higher risk for getting prostate cancer, and to study if certain genetic changes and family history can be used to help prevent or treat prostate cancer. There is NO treatment given in this study. Participants will undergo sampling of blood for prostate-specific antigen (PSA) and digital rectal exams. Based on these results and age, patients will be considered for biopsy and/or continued monitoring. Participants will undergo a baseline MRI evaluation with follow-up scans every 2 years as clinically indicated. Following initial evaluation, participants will be followed as clinically indicated, usually at 12 month intervals, to determine their PSA level, prostate cancer treatment (if relevant) and/or disease/survival status until death.

This study will evaluate whether a lifestyle intervention focused on weight loss, EMPOWER, reduces prostate cancer progression at 12 months among men with biochemical recurrence following local treatment for prostate cancer. Half of the men will be randomized to receive the EMPOWER intervention, while the other half will receive standard of care. Approximately 500,000 US men are living with biochemical recurrent prostate cancer (BCR). Therapies are needed to delay the appearance of metastatic disease and need for androgen deprivation therapy (ADT, hormonal therapy), which has significant adverse side effects. Observational evidence suggests that weight loss may slow the rate of disease progression. The EMPOWER trial will use an enhanced version of a remote weight loss intervention shown to yield clinically significant weight loss to test whether weight loss reduces prostate cancer progression at 12 months. EMPOWER has the potential to provide men with BCR a "first line therapy" to slow disease progression and delay the need for ADT. Importantly, this "treatment" is without significant side effects, and can improve overall health. Treatment – this study has 2 arms. EMPOWER EMPOWER is a multichannel, behavioral lifestyle intervention delivered remotely. The goals of EMPOWER are to induce a loss of 5% or more of initial weight within 6 months and to maintain these improvements at 12 and 24 months, by meeting dietary and physical activity goals. Coach-participant contacts will occur by phone and email, without in-person visits. Coaching contacts will be weekly for the first 12 weeks and then monthly thereafter. Men will have access to a web-based system that (1) provides support for behavioral methods of weight management and (2) allows coaches to review participant self-monitoring data and monitor participant progress towards goals. Men will record diet, exercise, and weight on the web or on a smart phone application. Standard of Care Men randomized to the standard of care group will continue to receive treatment from the mens' medical oncologists. These men will also be provided with a one page informative brochure on lifestyle recommendations adapted from the American Cancer Society Prostate Cancer Survivorship Care Guidelines, at the time of randomization. At the end of the trial, men in this arm will be offered a one-time counseling session with an intervention coach on healthy lifestyle.

Prostate cancer is often treated with radiation and ADT (ADT is androgen deprivation therapy, a type of hormonal therapy). Up to 30% of these cancers recur within 5 years of treatment. Researchers want to see if a new drug (M9241, a type of hormonal therapy) can help the immune system to fight prostate cancer. There is a growing body of evidence suggesting that stereotactic body radiation therapy (SBRT, a type of radiation treatment), which delivers highly conformal high-dose radiation, can promote anti-tumor immune responses both locally and systemically as well as synergize (enhance the effect) with immune checkpoint inhibitors and other forms of immunotherapy. The objectives of the study are to find what doses of M9241 are safe in people who are treated for prostate cancer, to see what effects M9241 has on the immune system and to evaluate whether immunocytokines (like M9241) can synergize with standard radiation + ADT therapy in prostate cancer. This study has 2 treatment arms: Arm A: Radiation only with Stereotactic Body Radiation Therapy (SBRT) SBRT to the prostate will be delivered in 5 fractions of radiation each of 7.25-8.0 Gy, every other day over the course of 10 business days (2-3 weeks). The total dose will be 36.25-40 Gy. Arm B: Radiation + M9241 SBRT to the prostate will be delivered in 5 fractions of radiation each of 7.25-8.0 Gy, every other day over the course of 10 business days (2-3 weeks). The total dose will be 36.25-40 Gy PLUS M9241 (dose level to be provided by treatment team) given by subcutaneous (SQ or SC) injection once every 4 weeks for 3 doses total. The first M9241 dose will be given 4 weeks after radiation has ended.

This phase II study investigates how well radium-223 (a type of radiation therapy) works in treating patients with castration-resistant prostate cancer (CRPC) than has spread to the bones (bone metastases). Prostate cancer is the most common cancer in men and the second leading cause of cancer death. Furthermore, many men with notably advanced disease have been found to have abnormalities in DNA repair. The purpose of this research is to study the role of a DNA repair pathway in prostate cancer, specifically in response to administration of radium-223, an FDA-approved drug known to cause DNA damage to cancerous cells. Understanding how defects in the DNA repair pathway affects radium-223 treatment of prostate, may help doctors help plan effective treatment in future patients. All participants will receive treatment. Patients receive standard of care radium Ra 223 dichloride (Alpharadin) given by intravenous (IV) bolus every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months during radium Ra 223 dichloride treatment.

MMR-deficient cancers of any type appear to be very sensitive to PD-1 blockade with pembrolizumab (Keytruda, a type of immunotherapy), and similar data are also beginning to emerge for nivolumab (Opdivo, a type of immunotherapy) and other immune checkpoint inhibitors. For men who previously received definitive treatment (prostatectomy and/or radiation therapy) for prostate cancer and subsequently develop detectable prostate specific antigen (PSA) levels, the clinical state is known as biochemically recurrent prostate cancer. The current standard of care treatment for patients with biochemically recurrent prostate cancer is either surveillance or androgen deprivation therapy (ADT, hormonal therapy). ADT has not been shown to provide a survival benefit in this setting, and the decision to initiate ADT will depend on patient preference and perceived risks of the disease. A non-hormonal therapy such as nivolumab would provide an alternative to ADT in patients with biomarker selected (i.e. genetic markers like dMMR, MSI-H, high TMB, or CDK12-altered) biochemically recurrent prostate cancer. Treatment – this study has 1 arm. Nivolumab is given at 480mg intravenously (IV) once every 4 weeks in clinic.

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 (a type of intravenous radiation therapy) in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, standard of care is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy (hormonal therapies). This study has 2 treatment arms: Arm A: 177Lu-PSMA-617 Participants will receive 177Lu-PSMA-617 intravenously (IV), once every 6 weeks for a planned 6 cycles, in addition to the Standard of Care hormonal therapy administered per the treating physician's order. Arm B: Standard of Care Participants will receive standard of care hormonal therapy administered per the treating physician's order.

This phase III trial compares the addition of apalutamide (a type of hormonal therapy), with or without targeted radiation therapy, to standard of care treatment versus standard of care treatment alone in patients with prostate cancer biochemical recurrence (a rise in the blood level of prostate-specific antigen [PSA] after treatment with surgery or radiation). Diagnostic procedures, such as positron emission tomography/computed tomography (PET/CT), may help doctors look for cancer that has spread to the pelvis. Androgens can cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET/CT results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer. This study has 4 treatment arms: Arm A: PET scan plus standard of care radiation and hormonal therapy Arm B: PET scan, standard of care radiation and hormonal therapy PLUS apalutamide by mouth (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. Arm C: PET scan, standard of care radiation and hormonal therapy PLUS apalutamide by mouth (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. Patients randomized to this arm will receive an additional PET scan at 12 months (or at second rise in PSA). Arm D: PET scan, standard of care radiation and hormonal therapy PLUS apalutamide by mouth (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. Patients randomized to this arm also receive targeted radiation therapy over 3-5 fractions in the absence of disease progression or unacceptable toxicity.

The purpose of this study is to compare any good and bad effects of using radium-223 (a type of radiation therapy) along with docetaxel (a type of chemotherapy) treatment versus using docetaxel alone. The study has 2 arms: Arm 1: Docetaxel Docetaxel 75 mg/m2 will be administered intravenously (IV) every three weeks for 10 doses. Prednisone will be given at a dose of 5mg orally twice daily. Arm 2: Docetaxel with Radium-223 Docetaxel 60 mg/m2 will be administered IV every 3 weeks for 10 doses. Radium-223 will be administered at 55 kBq/kg, 6 injections at 6 weeks intervals.

Metastatic castration sensitive and castration resistant prostate cancer (mCSPC and mCRPC) are prostate cancers that have spread to other parts of the body. Use of the drug docetaxel (Taxotere, a type of chemotherapy) with androgen deprivation therapy can improve survival for men with mCSPC. Researchers want to see if combining this treatment with other drugs can help delay the time it takes for mCSPC and mCRPC to get worse. The objective of this study is to determine if giving docetaxel with M7824 (Bintrafusp Alfa, a type of immunotherapy) and M9241 (NHS-IL12, a type of immunotherapy) is safe and effective for men with prostate cancer. This study has 2 treatment arms: Arm A: Docetaxel plus M9241 dose escalation with optional prednisone (a type of steroid) and ADT (androgen deprivation therapy, a type of hormonal therapy) as part of SOC (standard of care). Docetaxel 75mg/m^2 will be administered intravenously (IV) once every 21 days (a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC. M9241 at escalating doses will be administered as a subcutaneous (SC or SQ) injection once every three weeks. Prednisone and ADT will be given per standard of care (SOC) Arm B: Docetaxel plus M9241 plus M7824 with optional prednisone and ADT as part of SOC. Docetaxel and M9241 given the same as above plus M7824 (2400 mg) will be administered as a 1 hour intravenous (IV) infusion once every three weeks. Prednisone and ADT will be given per standard of care (SOC)

Prostate cancer is a heterogenous (diverse or varied) disease and recent genomic have highlighted specific germline and somatic mutations and alternative driver growth signaling pathways in patients with metastatic disease. This means that additional testing of blood and tumor tissue shows that different patients may have different causes of their prostate cancer, and/or different things that cause that cancer to grow. Abiraterone acetate plus prednisone (AA-P, a type of hormonal therapy) is an established standard of care for the treatment of participants with mCSPC and is included in widely accepted clinical treatment guidelines. Niraparib (a type of targeted therapy) is an investigational agent in the castration-sensitive cancer population and has been approved for the treatment of ovarian cancer. The addition of niraparib to the AA-P regimen may improve initial disease control and long-term outcomes compared with AA-P alone in a biomarker selected population (patients with a certain biomarker found through additional blood or tumor testing). The purpose of this study is help determine if that is true. This study has 2 treatment arms: Arm A: Niraparib with Abiraterone Acetate plus Prednisone (AA-P) Participants will receive the following in each 28-day treatment cycle: Niraparib 200 milligrams (mg), Abiraterone Acetate (AA) 1000 mg plus Prednisone 5 mg once daily. All medications are taken by mouth (orally or PO). Arm B: AA plus Prednisone (AA-P) Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus Prednisone 5 mg once daily. All medications are taken by mouth (orally or PO).

The study is investigating effectiveness, safety and tolerability of DNA-damage Response Agents (or Combinations), in participants with advanced/metastatic solid malignancies whose tumors contain molecular alterations, including metastatic castration-resistant prostate cancer (mCRPC). All subjects will receive treatment with Ceralasertib (a type of targeted therapy) tablets, administered orally (by mouth or po). Specific dose and dosing schedule will be provided by your treating physician.

The intent of this study is to establish the International Registry to Improve Outcomes in Men with Advanced Prostate Cancer (IRONMAN). The goal is to establish a population-based registry and recruit patients across academic (affiliated with a teaching hospital or medical school) and community practices from Australia, Brazil, Canada, Ireland, Sweden, Switzerland, the United Kingdom (UK), and the US. This cohort study will facilitate a better understanding of the variation in care and treatment of advanced prostate cancer across countries and across academic and community based practices. Detailed data will be collected from patients at study enrollment and then during follow-up, for a minimum of three years. Patients will be followed for overall survival, clinically significant adverse events, comorbidities (other diseases or illnesses that may arise), changes in cancer treatments, and PROMs (a type of quality of life questionnaire). PROMs questionnaires will be collected at enrollment, every three months for the first and second year, then every six months. As such, this registry will help identify the treatment sequences or combinations that optimize overall survival and PROMs (quality of life). By collecting blood at enrollment, time of first change in treatment and/or one year follow-up, this registry will further identify and validate molecular phenotypes (differences based on specific cells in the blood) of disease that predict response and resistance to specific therapeutics. Additionally, every effort will be made to collect blood specimen at each subsequent change in treatment. When feasible, existing tumor tissue may be collected for correlation with described blood based studies. All samples will be used for future research. This cohort study will provide the research community with a unique biorepository (collected of blood and tumor tissue) to identify biomarkers (specific cells in the blood or tumor tissue) of treatment response and resistance.

Prostate cancer is the second leading cause of cancer death in U.S. men. Radiation is an effective treatment for most patients with localized prostate cancer, but sometimes the tumor returns. Researchers want to see if a highly focused type of radiation can help. It is given in only 5 treatments. It is called stereotactic body radiation therapy (SBRT).

The objective of this trial is to study the maximum tolerated dose and side effects of stereotactic body radiation therapy in people with a local recurrence of prostate cancer after radiation. Re-irradiation with brachytherapy or stereotactic approaches has shown excellent rates of prostate cancer disease control with tolerable side effects. Using image guidance to allow highly focal re-irradiation may potentially increase the efficacy of re-irradiation.

Participants will be screened with blood tests, physical exam, and medical history. They may also have:

Magnetic resonance imaging (MRI) scan of the prostate.

PET/CT scan. Participants will get an injection of 18F-DCFPyL (a radiotracer used to detect prostate cancer cells) for the PET scan. They will lie very still on their back on the scanner table.

Small samples of prostate tumor tissue will be taken by a needle through the skin or rectum to see if the cancer is in the prostate. Small metal seeds will be placed into the prostate at the same time to help guide the radiation.

About 2 weeks later, participants will have a radiation treatment planning CT scan.

Participants will answer questions about their urine function, bowel function, erectile function, and mood.

Participants will receive SBRT. They will have 5 radiation treatments over 2 weeks.

Participants will have follow-up visits. They will have a physical exam, blood tests, and questionnaires.

Six months after ending SBRT, the 18F-DCFPyL PET/CT will be repeated.

Sometimes prostate cancer comes back after a person’s prostate is removed. In this case, radiation is a common treatment. Radiation kills prostate cancer cells. It can be very effective. It is usually given in short doses almost every day for 6 or 7 weeks. Researchers want to see if a shorter schedule can be equally as effective. They want to see if a shorter schedule causes the same or fewer side effects. Usually, radiation is used to treat the entire area where the prostate was before surgery. In some patients, an area of tumor can be seen on scans. Researchers are also trying to see if they can give a lower dose to the area usually treated with radiation (the entire prostate bed) if the full dose is given to the tumor seen on scans. There will be two arms on this study: Arm 1 - Dose to prostate bed with integrated boost Radiation will be delivered to an escalated dose to areas of recurrent prostate cancer identified on imaging and a reduced dose will be delivered to the entire prostate bed. Arm 2 - Dose to prostate bed Radiation will be delivered to the prostate bed only (this is considered standard of care).

Prostate cancer is the second leading cause of cancer deaths in American men. Few options exist to create images of this type of cancer. Researchers think an experimental radiotracer called 18F-DCFPyL could find sites of cancer in the body. Participants will have 18F-DCFPyL injected into a vein. About 2 hours later they will have a whole-body Positron Emission Tomography/Computed Tomography (PET/CT). For the scan, participants will lie on their back on the scanner table while it takes pictures of the body. This lasts about 50 minutes. On another day, participants will have 18F -NaF injected into a vein. About 1 hour later, they will have a whole-body PET/CT. If the 18F-DCFPyL PET/CT is positive participants will be encouraged to undergo a biopsy of one of the tumors. The biopsy will be taken through a needle put through the skin into the tumor. Participants will be followed for 1 year. During this time researchers will collect information about their prostate cancer, such as PSA levels and biopsy results. There is no treatment given on this protocol.

This is a study to evaluate the safety and clinical activity of the combination of olaparib (Lynparza, a type of targeted therapy) and high-dose intravenous (IV) ascorbate (vitamin C, a type of supplement or nutraceutical), as second or later line of therapy, in castration resistant prostate cancer patients with no known DNA repair gene mutations (DDRm). In brief, the primary endpoint is PSA response, defined by a 50% reduction in PSA from baseline . The secondary endpoints are assessing the PSA doubling time (how quickly PSA rises), radiographic (imaging like CT or bone scans) and PSA progression free survival (PFS), safety and tolerability, and measuring overall survival. This study has one treatment arm: Olaparib and Vitamin C Olaparib will be administered at 300 mg by mouth (orally, PO), twice daily; ascorbate will be administered at 1 g/kg intravenously (IV) twice weekly at least 24 hours apart, until objective disease progression or unacceptable toxicities or patient withdrawal for other reasons.

The primary objective of this study is to compare the progression free survival (PFS) of patients with metastatic castration-resistant prostate cancer treated with enzalutamide (Xtandi, a type of hormonal or anti-androgen therapy) in combination with LY2157299 (a type of targeted therapy) versus enzalutamide alone. The hypothesis is that patients receiving enzalutamide in combination with LY2157299 will have longer progression free survival than patients receiving enzalutamide alone. This study has 2 treatment arms: Arm A: Enzalutamide + LY2157299 Enzalutamide 160mg taken orally (by mouth, PO) once a day on days 1-28 of each cycle PLUS LY2157299 150 mg taken orally twice a day on days 1-14 of each cycle. Arm B: Enzalutamide alone Enzalutamide 160mg taken orally (at home) once a day on days 1-28 of each cycle.

This is an effectiveness seeking trial, utilizing sequential arms as a means to identify signals of activity for combinations of immunotherapy in metastatic castrate resistant prostate cancer (mCRPC) patients. PD-1/PD-L1 signaling appears to be a major inhibitor of activated T cell anti-tumor immune responses. The rapid, deep and durable responses seen in various malignancies with PD-1/PD-L1 targeted agents demonstrate that blockade of this axis is key to facilitating immune responses within the tumor microenvironment (TME). Prostate cancer is poorly recognized by T cells. Lack of an immune response is one explanation for the lower response rates (<15%) observed with anti-PD-1/PD-L1 therapies for prostate cancer. Increasing response rates will likely require therapeutic correction of multiple immune deficits by combining immunotherapies. In treating of mCRPC, we hypothesize that these agents and their effects will be complementary. Tumor-specific T cells generated by vaccine may become more functional in a TME following treatment with M7824 and Epacadostat. ALT-803 can further enhance the activity of these vaccines. This study has 7 arms (although some B arms are expansions of previous A arms): Arm 1.1: M7824 + ALT-803 M7824 at 1,200 mg given intravenously (IV) once every 2 weeks ALT-803 at 10-20 mkg/kg given by subcutaneous injection once every 2 weeks Arm 2.1A M7824 + BN-Brachyury M7824 at 1,200 mg given IV once every 2 weeks MVA-BN-Brachyury given by subcutaneous injection for 2 doses, 2 weeks apart FPV-Brachyury given by subcutaneous injection 2 weeks after the second dose of MVA- BN-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 month. Arm 2.2A M7824 + BN-Brachyury + ALT-803 M7824 at 1,200 mg given IV once every 2 weeks ALT-803 at 10-20 mkg/kg given by subcutaneous injection every 2 weeks MVA-BN-Brachyury given by subcutaneous injection for 2 doses, 2 weeks apart FPV-Brachyury given by subcutaneous injection 2 weeks after the second dose of MVA- BN-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 month. Arm 2.3A M7824 + BN-Brachyury + ALT-803 + Epacadostat M7824 at 1,200 mg given IV once every 2 weeks ALT-803 at 10-20 mkg/kg given by subcutaneous injection every 2 weeks MVA-BN-Brachyury given by subcutaneous injection for 2 doses, 2 weeks apart FPV-Brachyury given by subcutaneous injection 2 weeks after the second dose of MVA- BN-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 month. Epacadostat at 100 mg taken orally twice daily (200 mg total) Arm 2.1B M7824 + BN-Brachyury M7824 at 1,200 mg given IV once every 2 weeks MVA-BN-Brachyury given by subcutaneous injection for 2 doses, 2 weeks apart FPV-Brachyury given by subcutaneous injection 2 weeks after the second dose of MVA- BN-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 month. Arm 2.2B M7824 + BN-Brachyury + ALT-803 M7824 at 1,200 mg given IV once every 2 weeks ALT-803 at 10-20 mkg/kg given by subcutaneous injection every 2 weeks MVA-BN-Brachyury given by subcutaneous injection for 2 doses, 2 weeks apart FPV-Brachyury given by subcutaneous injection 2 weeks after the second dose of MVA- BN-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 month. Arm 2.3B M7824 + BN-Brachyury + ALT-803 + Epacadostat M7824 at 1,200 mg given IV once every 2 weeks ALT-803 at 10-20 mkg/kg given by subcutaneous injection every 2 weeks MVA-BN-Brachyury given by subcutaneous injection for 2 doses, 2 weeks apart FPV-Brachyury given by subcutaneous injection 2 weeks after the second dose of MVA- BN-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 month. Epacadostat at 100 mg taken orally twice daily (200 mg total)

This is a study of vobramitamab duocarmazine (MGC018, a type of targeted therapy) in combination with lorigerlimab (a type of immunotherapy). The study is designed to characterize safety, tolerability, drug activity, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including metastatic castration resistant prostate cancer (mCRPC) and renal cell carcinoma (RCC) will be enrolled. All participants will receive treatment. Vobramitamab duocarmazine and lorigerlimab will be given intravenously (IV) once every 4 weeks. Dosage level will be provided by the treatment team.

This randomized double-blinded Phase II clinical trial will evaluate the bioavailability, safety, effectiveness and validate the mechanism by which a standardized formulation of whole Green Tea Catechin, (Sunphenon® 90D, a type of nutritional supplement or neutraceutical) containing 405 mg versus Placebo, administered for 24 months in a cohort of men with low to intermediate grade prostate managed on active surveillance. This study has 2 arms: Arm A: Sunphenon® 90D Participants will be administered a standardized formulation of whole Green Tea Catechin by mouth (PO, orally) twice daily for 24 months. The daily dose of Green Tea Catechin will be taken in divided doses, three capsules in the morning and 3 capsules in the evening, with food (within one hour of eating a substantial meal). On the day of monthly follow-up visit, capsules should be taken within 4 hours of visit and blood draw for required lab work. If the participant is scheduled to come in the afternoon, dose should be taken with lunch that day instead of with dinner for that day. Arm B: Placebo Participants will be administered a placebo by mouth twice daily for 24 months. The daily dose of placebo will be taken in divided doses, three capsules in the morning and 3 capsules in the evening, with food (within one hour of eating a substantial meal). On the day of monthly follow-up visit, capsules should be taken within 4 hours of visit and blood draw for required lab work. If the participant is scheduled to come in the afternoon, dose should be taken with lunch that day instead of with dinner for that day.

The purpose of this study is to assess the safety and efficacy of pembrolizumab (Keytruda or MK-3475, a type of immunotherapy) combination therapy in patients with metastatic castrate resistant prostate cancer (mCRPC). It is thought that combining pembrolizumab with other therapies will be more effective than those therapies alone. This study has 8 treatment arms: Arm 1: Pembrolizumab + Olaparib (Lynparza, a type of targeted therapy) Participants will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week dosing cycle (Q3W) and olaparib 400 mg capsules or 300 mg tablets by mouth (PO or orally) twice a day (BID) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with olaparib will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug. Arm 2: Pembrolizumab + Docetaxel (Taxotere, a type of chemotherapy) + Prednisone (a steroid) Participants will receive pembrolizumab 200 mg IV on Day 1 Q3W, docetaxel IV on Day 1 Q3W, and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Participants will only be permitted to receive a maximum of 10 cycles of docetaxel and prednisone. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Arm 3: Pembrolizumab + Enzalutamide (Xtandi, a type of hormonal therapy) Participants will receive pembrolizumab 200 mg IV on Day 1 Q3W and enzalutamide 160 mg PO every day (QD) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with enzalutamide will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug. Arm 4: Pembrolizumab + Abiraterone (Zytiga, a type of hormonal therapy) + Prednisone (a steroid) Participants will receive pembrolizumab 200 mg IV on Day 1 Q3W, abiraterone acetate 1000 mg PO QD and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Arm 5: Pembrolizumab + Lenvatinib (Lenvima, a type of targeted therapy) Participants will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Arm 6: Pembrolizumab + Vibostolimab coformulation (a type of targeted therapy) Participants with AC mCRPC in Cohort G will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Arm 7: Pembrolizumab + Carboplatin + Etoposide Participants will receive pembrolizumab 200 mg IV on Day 1 Q3W + carboplatin IV on Day 1 Q3W + etoposide IV on Days 1, 2, and 3 Q3W. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin + etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 or 2 of the 3 drugs due to adverse events in the combination may continue the study with the other combination drug/drugs. Arm 8: Carboplatin + Etoposide Participants will receive carboplatin IV on Day 1 Q3W + etoposide IV on Days 1, 2, and 3 Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin + etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

This is a Phase II, open-label, 2-arm, multicenter, international study designed to evaluate the effectiveness of zenocutuzumab (a type of targeted therapy) in combination with enzalutamide (Xtandi, a type of hormonal therapy) OR abiraterone (Zytiga, a type of hormonal therapy) in patients with metastatic castration resistant prostate cancer (mCRPC). This study has one arm for mCRPC: Zenocutuzumab + Enzalutamide OR Abiraterone Participants will receive intravenous (IV) infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with the AR targeting (hormonal therapy) agent they experienced disease progression on prior to study entry: Enzalutamide 160 mg orally (by mouth, PO) once daily OR abiraterone 1000 mg orally once daily with prednisone 5 mg orally twice daily.

The purpose of this study is to determine whether BMS-986249 (a type of immunotherapy) both by itself and in combination with Nivolumab (Opdivo, a type of immunotherapy) is safe and tolerable in the treatment of advanced solid tumors, including Metastatic castration-resistant prostate cancer (mCRPC). Prostate cancer patients will receive: BMS-986249 + nivolumab – specific dosing and specific dosing schedule will be provided by your treating physician.

This is a first-in-human, Phase 1/2 multicenter, open-label, dose escalation and expansion study of AO-176 (a type of immunotherapy) in patients with solid tumors. Part A of this study will examine escalating repeat doses of AO-176 monotherapy in patients with select advanced solid tumors, including castration resistant prostate cancer (CRPC), for which standard therapy proven to provide clinical benefit does not exist or is no longer effective. All subjects will receive AO-176, given orally (po or by mouth). Specific dosing and specific dosing schedule will be provided by your treating physician.

This phase III trial compares the effect of adding darolutamide (Nubeqa, a type of hormonal therapy) to androgen deprivation therapy (ADT, a type of hormonal therapy) versus ADT alone after surgery for the treatment of high-risk prostate cancer. ADT reduces testosterone levels in the blood. Testosterone is a hormone made mainly in the testes and is needed to develop and maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. It also plays role in prostate cancer development. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. Giving darolutamide with ADT may work better in eliminating or reducing the size of the cancer and/or prevent it from returning compared to ADT alone in patients with prostate cancer. This study has 2 treatment arms: Arm A: ADT + placebo Patients receive standard of care ADT (chosen by patient and treatment provider) PLUS placebo by mouth (PO, orally) 4 times daily for 52 weeks (1 year). Arm B: ADT + darolutamide Patient receive standard of care ADT (chosen by patient and treatment provider) PLUS darolutamide by mouth 4 times daily for 52 weeks.

This research is being done to see if an investigational radioactive imaging agent (radiotracer) called 18F-DCFPyL can help us find prostate cancer at its original site in the prostate gland and in distant sites (bone, lymph nodes) in men diagnosed with prostate cancer before surgery. The investigators propose to evaluate the feasibility of using a novel small molecule PET radiotracer, DCFPyL to target prostate cancer prostate-specific membrane antigen (PSMA). PSMA is a well studied cell surface marker of prostate cancer with increased expression associated with higher tumor grade and advanced metastatic tumors. More specifically it is associated with a higher Gleason score and there is evidence it can serve as a potential marker for prostate tumor carcinogenesis, progression and as a marker of androgen deprivation therapy (ADT, hormonal therapy) response. This small molecule PET radiotracer specifically targeting an important prostate specific marker of signaling dynamics following ADT, tumor progression and metastatic potential warrants validation as non-invasive imaging biomarker for PSMA expression and prostate cancer detection. This study does not provide any treatment. Participants will undergo a pelvic DCFPyL PET-MRI fusion or PET/MRI compared before and after 2-3 months of ADT.

For men with prostate cancer that involves the nearby lymph nodes standard treatment varies. Many men undergo radical prostatectomy (total removal of the prostate) along with the removal of nearby lymph nodes. Other men may opt for androgen deprivation therapy (ADT, a therapy that blocks testosterone, hormonal therapy) using the two drugs leuprolide and abiraterone (Zytiga) with or without radiation. This research is being done to investigate whether the use of leuprolide and abiraterone, when given in combination with a drug that blocks a molecule that senses oxygen needs by cancer cells, belzutifan (a type of targeted therapy), can kill cancer cells in the body prior in men who are planning on having the prostate surgically removed. This study has one treatment arm. Participants will be treated with neoadjuvant (before surgery) therapy for a total of 3 months (12 weeks) prior to prostatectomy. Therapy will consist of leuprolide acetate, abiraterone acetate, and belzutifan. Each drug will be dosed at its respective FDA-approved dosage. These dosages are as follows: leuprolide acetate one dose at 22.5 mg depot intramuscular injection, abiraterone acetate 1000 mg by mouth (orally, PO) once daily, and belzutifan120 mg administered by mouth once daily. All men will also be treated with prednisone 5 mg by mouth twice daily while on abiraterone acetate in order to reduce side effects.

This is an open label, multi center, Phase 1 dose escalation study of PF 06821497 (a type of targeted therapy) administered orally as a single agent to patients with SCLC, CRPC, DLBCL and FL, or in combination with standard of care therapy (SOC). This study has multiple treatment arms with multiple dose levels. All subjects will receive the study drug PF 06821497. Dose level and dosing schedule will be provided by your treatment team. Standard of care treatment will also be provided by your treatment team.

This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, preliminary antitumor activity, and effects of XL092 (a type of targeted therapy) administered alone, in combination with atezolizumab (Tecentriq, a type of immunotherapy), and in combination with avelumab (Bavencio, a type of immunotherapy) to subjects with advanced solid tumors. This study has 3 treatment arms: Arm A: XL092 alone XL092 will be given orally (by mouth or PO). Dosage and dosing schedule to be provided by treatment team. Arm B: XL092 + Atezolizumab XL092 will be given orally (by mouth or PO). Dosage and dosing schedule to be provided by treatment team. Atezolizumab is administered as a 1200 mg IV (intravenously) infusion once every 3 weeks. Arm C: XL092 + Avelumab XL092 will be given orally (by mouth or PO). Dosage and dosing schedule to be provided by treatment team. Avelumab is administered as an 800 mg IV infusion once every 2 weeks.

The typical standard of care for patients with localized, intermediate risk prostate cancer is radical prostatectomy, which involves the surgical removal of the prostate. Although radical prostatectomy is effective in terms of controlling the cancer, it may leave men with significant long-term effects in urinary, sexual function like erectile dysfunction and/or incontinence (loss of bladder control), thus reducing quality of life. Preservation of continence (ability to control your bladder) and potency (ability to achieve erection and/or ejaculation) may be significant concerns for men. Targeted ablation of localized prostate cancer using MRI-guided technology is becoming a favorable option for many men who wish to have their cancer treated but do not wish to compromise their urinary and sexual functions. The TULSA Procedure is a new, minimally invasive technique that uses real-time MRI-guided technology to guide the delivery of high-energy ultrasound to precisely, and in a customized fashion specific to you, heat and kill the prostate cancer tissue while protecting important surrounding body parts that are important for preserving urinary and sexual function. Minimally invasive here means that the procedure is performed through natural openings in your body (the urethra) instead of creating larger openings like traditional surgery or minimally invasive surgery. This study has 2 treatment arms: Arm A: Radical prostatectomy If you are in this group, you will get the standard of care treatment used to treat this type of cancer: radical prostatectomy. You will undergo this procedure as per standard clinical practice. A radical prostatectomy is a surgical procedure that removes the prostate gland. This is done by making a surgical incision and removing the prostate gland. Arm B: TULSA procedure If you are in this group, you will get the TULSA Procedure. The TULSA Procedure is a minimally invasive procedure that uses directional ultrasound to produce very high temperature to ablate (destroy) targeted prostate tissue. The procedure is performed in an MRI suite (the physician can see the prostate at all times throughout the procedure) and uses the TULSA-PRO system to ablate prostate tissue. The procedure combines real-time MRI with robotically driven directional thermal ultrasound to deliver predictable, physician-prescribed ablation of the prostate. Minimally invasive here means that the procedure is performed through natural openings in your body (the urethra) instead of creating larger openings like in traditional surgery.

The purpose of this study is to assess the safety, tolerability and preliminary effectiveness of CC-94676 (a type of hormonal therapy) in men with progressive metastatic castration resistant prostate cancer. Prostate cancers initially need the male hormone testosterone for growth. Hormone therapies that lower the level of testosterone are among the most effective treatments for prostate cancers that have spread to other organs (metastasized). Over time, many prostate cancers continue to grow despite hormonal therapies; these are called “castration-resistant prostate cancers” (CRPC). The androgen receptor is a protein that is important in the development and progression of prostate cancer. CC-94676 is an investigational drug designed to inhibit prostate cancer growth by blocking the androgen receptor. This study has 1 treatment arm: Arm A: CC-94676 CC-94676 is taken by mouth (orally or PO), dosing and schedule will be provided by the treatment team.

The primary purpose of this study is to investigate the safety and tolerability and to determine the maximum tolerated dose of DS-1062a (Datopotamab Deruxtecan, a type of targeted therapy). It is the first time the drug has been used in humans. All subjects will receive treatment. DS-1062a is given intravenously (IV) in clinic. Dosing and schedule will be provided by the treatment team.

This phase II trial studies how well green tea catechins work in preventing progression of prostate cancer from a low risk stage to higher risk stages in men who are on active surveillance. Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea. Green tea catechins may stabilize prostate cancer and lower the chance of prostate growing. This study has 2 treatment arms: Arm A: Green tea catechins Patients receive green tea catechins by mouth (orally, PO) twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity. Arm B: Placebo Patients receive placebo by mouth twice daily for up to 6 months.

Prostate cancer is the second leading cause of cancer deaths in American men. When prostate cancer is confined to the prostate there is a high chance of cure. However, if it is outside the prostate or comes back after treatment, additional therapy may be needed. Current methods of imaging prostate cancer are limited. Researchers want to see if a radiotracer called 18F-DCFPyL can identify prostate cancer in patients who have a high risk of cancer spreading outside the prostate or who have signs of recurrent cancer after treatment. Participants will be divided into 2 groups: Group 1 will be men with cancer that has been newly diagnosed as high risk by their doctor who are scheduled to have prostate removal surgery or undergo biopsy before radiation therapy. Group 2 will be men who have presumed prostate cancer relapse after prostate removal surgery or radiation therapy. Both groups will have scans taken. Participants will lie still on a table in a machine that takes pictures of their body. 18F-DCFyL will be injected by intravenous (IV) line. Participants will be contacted for follow-up after scans. There is no treatment given on this protocol.

Prostate cancer is the leading cause of new cancer diagnoses and the second most common cause of cancer-related death in American men. Prognosis is especially poor for men with metastatic castration resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA) is highly expressed on malignant prostate tissue but shows limited expression on normal tissue. As such, PSMA is an excellent research target for treatment of mCRPC. REGN4336 is a PSMAxCD3 bispecific antibody designed to facilitate T-cell–mediated killing of PSMA-expressing tumor cells (a type of immunotherapy). In preclinical models, REGN4336 demonstrated strong PSMA-dependent antitumor activity. Preclinical data also support clinical research into the combination of REGN4336 with cemiplimab (Libtayo, another type of immunotherapy) for treating mCRPC. This study has 2 treatment arms: Arm A: REGN4336 alone Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection. Arm B: REGN4336 + Cemiplimab REGN4336 administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection PLUS Cemiplimab administered concomitantly every 3 weeks (Q3W) by intravenous (IV) infusion.

This is a prospective, open-label Phase 2 study to evaluate copper Cu 64 PSMA I+T injection (a type of radiotracer or Radiolabeled Receptor-Targeted Diagnostic Product) for PET/CT imaging in patients with recurrent metastatic prostate cancer after radical prostatectomy or radiation therapy. This study does not provide treatment. Each patient will be administered a 7-9 mCi intravenous (IV) dose of copper Cu 64 PSMA I+T injection. PET/CT images will be acquired for all patients at 1 hour and 4 hours post copper Cu 64 PSMA I+T injection.

This trial investigates how well apalutamide (Erleada, a type of hormonal therapy) before surgery works in treating patients with prostate cancer that is confined to the prostate gland. Testosterone can cause the growth of prostate cancer cells. Apalutamide blocks the use of testosterone by the tumor cells. Giving low dose apalutamide before prostate surgery may lead to lowered PSA levels in men with prostate cancer that is confined to the prostate gland. This study has 1 arm: Apalutamide: The first 40 patients taking part in this trial receive apalutamide by mouth (orally or PO) 3 times per week for 4-8 weeks before prostate surgery in the absence of disease progression or unacceptable side effects. Based on PSA levels of the first 40 patients, the next group of 40 patients receive apalutamide either once per week or once daily for 4-8 weeks before prostate surgery in the absence of disease progression or unacceptable side effects. Patients may receive apalutamide for up to 12 weeks before prostate surgery (in the event surgery is delayed).

Olaparib (a type of targeted therapy called a PARP inhibitor) has demonstrated preliminary effectiveness in metastatic castration-resistant prostate cancer. While PARP inhibition is showing promise in initial studies, reserving its use for metastatic castration-resistant patients may not be the optimal timing for olaparib therapy in. PARP inhibition has not been tested in earlier disease states for prostate cancer. The hypothesis is that olaparib may show anti-tumor effects (targeting cancer cells not yet visible on CT or bone scans) in high risk patients following radical prostatectomy. Patients will take olaparib 300 mg orally (at home) twice daily, approximately 12 hours apart. Each cycle will be 28 days.

The purpose of the study is to assess if the addition of darolutamide (Nubeqa, a type of hormonal therapy) to androgen deprivation therapy (ADT, hormonal therapy) compared with ADT alone would result in superior clinical effectiveness in participants with metastatic hormone-sensitive prostate cancer (mHSPC) by progression-free survival. The researchers want to learn how long it takes for the cancer to get worse (also known as "progression-free survival") by either increasing symptoms, new metastases, PSA rise or death. All participants will be on treatment and take darolutamide with ADT until their cancer spreads, they have a medical problem, or they leave the study. The results will then be compared with patients' results from another study who received ADT alone (CHAARTED). This study will also assess safety by gathering adverse event information throughout the duration of the study. An adverse event is any medical problem, related or not to study treatment that a participant has during a study. The study drug, darolutamide, is already available for doctors to prescribe to patients with prostate cancer that has not yet spread to other parts of the body. It works by blocking a protein called a receptor from attaching to a hormone called androgen that is found in men. This protein can also be found in prostate cancer cells. ADT is a treatment that doctors are currently able to prescribe to patients with mHSPC. ADT is used to lower the amount of the androgen hormone. This study has 1 treatment arm: Darolutamide + ADT Participants will receive darolutamide 300 mg per tablet, oral administration (by mouth or PO) with food PLUS ADT (LHRH agonist/antagonist or orchiectomy).

This study will assess the effectiveness and safety of capivasertib (a type of targeted therapy) plus docetaxel (Taxotere, a type of chemotherapy) versus placebo plus docetaxel in participants with metastatic castration resistant prostate cancer (mCRPC). All participants will receive the docetaxel with steroid therapy and receive androgen deprivation therapy. The intention of the study is to demonstrate that the combination of capivasertib plus docetaxel is superior to placebo plus docetaxel with respect to the overall survival of study participants, when overall survival is defined as the time from randomization until the date of death due to any cause. This study has 2 treatment arms: Arm A: Capivasertib + Docetaxel Capivasertib 320 mg (2 tablets) given orally (by mouth or PO) on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle until disease progression or unacceptable toxicity develops, death, or if the patient requests to stop the study treatment PLUS docetaxel given by intravenous (IV) infusion, 75 mg/m2 BSA, on Day 1 of the 21-day cycles for up to 6 to 10 cycles, according to standard of care practices. Arm B: Placebo + Docetaxel Placebo matched to capivasertib in appearance (2 tablets) given orally on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle until disease progression or unacceptable toxicity develops, death, or if the patient requests to stop the study treatment PLUS docetaxel given by intravenous (IV) infusion, 75 mg/m2 BSA, on Day 1 of the 21-day cycles for up to 6 to 10 cycles, according to standard of care practices.