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 standard of care for obese men starting Androgen deprivation therapy (ADT) is physician based dietary and exercise counseling. Interventions to lessen the harmful effects of ADT are needed yet have been limited. Exercise is one strategy that has been attempted however there is conflicting data as to whether or not exercise effectively improves body mass, results in sustained weight loss, improvements in metabolic risk profiles including glucose tolerance and lipid profiles in men starting ADT or has any effect of progression of cancer. Dietary interventions have been attempted without clear improvement in weight, metabolic factors, quality of life or cancer progression. Bariatric arterial embolization (BAE), given it results in weight loss in obese men and women without cancer, may be able to stave off the harmful side effects of ADT by inducing weight loss. Therefore, the investigators hypothesize that Bariatric Arterial embolization (BAE), done prior to initiation of ADT, will mitigate the weight gain and metabolic side effects associated with ADT, by inducing weight loss of at least 5% in obese men with biochemical recurrent prostate cancer starting ADT. The primary objective is to determine if BAE, done prior to ADT initiation in obese men (with obesity related comorbid condition) with biochemically recurrent prostate cancer, can induce 5% or greater weight loss at 6 months. All subjects receive: Diet and exercise with BAE After enrollment in the clinical trial, all men will be enrolled in diet and exercise counseling through the weight management program for a total of 4 weeks. If participants lose >5 pounds of total body weight from weight management alone in the first 4 weeks, these participants will be excluded from study and will not undergo BAE but will be encouraged to continue with weight management. Those still enrolled will undergo BAE. Within 7 days of BAE, men will be given ADT (Lupron subcutaneous injection). Device: Bead Block 300-500 um These patients will undergo embolization with 300-500µm Bead Block particles. Behavioral: Weight Management All participants will be enrolled in weight management through the Johns Hopkins Weight Management Center. During weeks -4 through 0, participants will be required to go to weekly visits. Weight management will include counseling on diet, exercise and behavior change. Food programs, pharmacotherapy and other procedures will not be utilized. Drug: Lupron 22.5 mg will be given as a single intramuscular (IM) or subcutaneous (SC or SQ) injection once every 12 weeks according to the standard of care for prostate cancer. If leuprolide acetate, 22.5 mg for 3-month administration is not available, a suitable substitute may be allowed upon approval by the principal investigator.

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.

"This is a multicenter Phase 1b, open-label study to assess safety, tolerability, and preliminary effectiveness of cabozantinib (Cabometyx, a type of targeted therapy) taken in combination with atezolizumab (Tecentriq, a type of immunotherapy) in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), and castration-resistant prostate cancer (CRPC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and effectiveness of the combination treatment in these tumor types. Dose escalation: Subjects will be enrolled in cohorts of 3-6 subjects for evaluation of cabozantinib tablet dose of either 20 mg, 40 mg, and 60 mg taken orally (PO) once daily in combination with standard dosing regimen of atezolizumab (1200 mg given by intravenous infusion once every 3 weeks). Expansion: Atezolizumab 1200 mg given by intravenous infusion once every 3 weeks will be given in combination with cabozantinib administered orally daily at the determined recommended dose from the Dose Escalation Stage. "

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

There currently are few treatments for early and/or less-aggressive prostate cancer. This trial tests a cooled laser applicator system guided by ultrasound imaging (as opposed to MRI) as a treatment. Before the procedure, participants will need to have a needle biopsy. The duration of the hospital stay is 12 days and the follow-up involves six visits over three years to track progress.

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.

Some people with prostate cancer have a rise in prostate-specific antigen (PSA). This can happen even after treatments like radiation and surgery. Androgen deprivation therapy (ADT) drugs and close monitoring are one standard way to treat this group of people. Another way is to monitor people and their PSA values over time. Researchers want to see if a combination of new drugs can help these people. The focus of this study is to determine if combination immunotherapy with immune-cell mobilizing vaccines can initiate an immune response in the first 4 months of treatment that is then augmented by an immune checkpoint inhibitor in the following 3 months. Current and previous clinical trials have demonstrated that single agent immunotherapy can impact PSA in patients in this population. Some participants will have close monitoring with four monthly PSA checks. All participants will get two study drugs as shots under the skin (SC injection). They will get the third drug in a vein (IV). They will get the drugs over at least 7 months. Their vital signs will be checked before they get the drugs and for up to 1 hour after. Participants will have frequent study visits. This study has 1 arm: Arm 1: Combination Immunotherapy After surveillance period, patients will be treated with 2 vaccines concurrently, Prostvac and CV301, during months 1-4. For months 5-7, MSB0011359C [an anti-PD-L1 antibody (avelumab) with TGFbeta-Trap molecule] will be added to the regimen. Treatment drugs: PROSTVAC-V Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824) Fully human bi-functional fusion protein that combines lgG1 anti-PD-L1 and TGFbetaRII as a monoclonal antibody administered by IV infusion over 1 hour. CV301 Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.

This trial is a study of the quality of high-dose-rate brachytherapy at the National Institutes of Health. Brachytherapy is a form of radiation therapy that uses a hollow implant instead of an external beam to deliver radiation. This allows for a higher dose of radiation to be delivered directly to the tumor while causing minimal damage to the surrounding tissue. Participants will receive the brachytherapy treatments and then have follow-ups at 1, 3, 6, 9, and 12 months post-brachytherapy.

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 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 and immunotherapy) versus enzalutamide alone. The hypothesis is that patients receiving enzalutamide in combination with LY2157299 will have longer PFS than patients receiving enzalutamide alone.

Treatment is either:

1. Enzalutamide 160mg taken orally (at home) once a day on days 1-28 of each cycle PLUS LY2157299 150 mg taken orally (at home) twice a day on days 1-14 of each cycle, OR

2. Enzalutamide 160mg taken orally (at home) once a day on days 1-28 of each cycle.

This phase III trial studies how well adding apalutamide (a type of hormonal therapy), abiraterone acetate (Zytiga, a type of hormonal therapy), and prednisone (a steroid) to the usual hormone therapy and radiation therapy works compared to the usual hormone therapy and radiation therapy in treating patients with node-positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or slow the growth of prostate cancer cell growth by blocking the androgens. Abiraterone acetate blocks some of the enzymes needed for androgen production and may cause the death of prostate cancer cells that need androgens to grow. Prednisone may help abiraterone acetate work better by making tumor cells more sensitive to the drug. Adding apalutamide and abiraterone acetate with prednisone to the usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading or extend time without disease spreading compared to the usual approach. This study has 2 treatment arms: Arm A: Radiation and hormonal therapy (standard of care) Patients receive standard of care hormone therapy per physician discretion for 24 months. Patients also undergo standard of care pelvis and prostate bed radiation therapy 5 days per week over 7-8 weeks beginning within 56 days after first hormone injection if the injection is not started prior to registration or within 90 days after first hormone injection if the injection is started prior to registration in the absence of disease progression or unacceptable toxicity. Arm B: Radiation and hormonal therapy PLUS apalutamide, abiraterone acetate and prednisone Patients receive standard of care hormone therapy and radiation therapy as in Arm A. Patients also receive apalutamide by mouth (PO) once daily (QD), abiraterone acetate PO QD, and prednisone PO QD or BID (twice daily) on days 1-90. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

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.

The purpose of this study is to assess the effectiveness and safety of the combination of pembrolizumab (Keytruda, a type of immunotherapy) and enzalutamide (Xtandi, a type of hormonal therapy) in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC, are abiraterone-naïve (Zytiga, a type of hormonal therapy), or are intolerant to or progressed on abiraterone acetate. There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide for Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide for Radiographic Progression-free Survival (rPFS), meaning the cancer is not visible on imaging/scans. This study has 2 arms: Arm 1: Pembrolizumab + Enzalutamide Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered in clinic on Day 1 of each 21-day cycle (every 3 weeks) for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered orally (PO) once a day (QD) continuously. Arm 2: Placebo + Enzalutamide Participants receive placebo by IV infusion administered in clinic on Day 1 of each 21-day cycle (every 3 weeks) for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered PO QD continuously.

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.

The purpose of this study is to test the safety and effectiveness of nivolumab (Opdivo, a type of immunotherapy) with docetaxel (Taxotere, a type of chemotherapy) in men with advanced castration resistant prostate cancer who have progressed after second-generation hormonal therapy. This study has 2 arms: Arm A: Nivolumab + docetaxel + prednisone – specific dosing and dosing schedule will be provided by your treating physician. Arm B: Placebo + docetaxel + prednisone – specific dosing and dosing schedule will be provided by your treating physician.

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 specific antigen (PSA) has been used for early detection and monitoring of patients with prostate cancer who receive a variety of treatments. Due to the widespread use of serum PSA to monitor for prostate cancer recurrence following primary treatment, there exists a group of men with a rising PSA as their only evidence of recurrence. These patients may not demonstrate clinical or radiographic evidence of disease progression for an average 8 years from the time of detectable PSA to detectable metastatic disease by standard imaging. Currently there are limited treatment options for these patients that may delay disease progression or improve survival, including salvage radiation for prior surgical patients, hormonal therapy, and active surveillance. Although some surgical patients are candidates for salvage radiation, not all patients will want salvage radiation. Even the early initiation of hormonal has not demonstrated a survival benefit, although data suggests an advantage for early hormone therapy in the setting of metastatic regional lymph nodes. Furthermore, early initiation of androgen ablation is associated with significant morbidity and impact on quality of life, including fatigue, hot flashes, loss of libido, decreased muscle mass, and osteoporosis with long term use. This group of relatively well men with biochemical recurrence are currently offered androgen ablation therapy or active surveillance (regular PSA monitoring and annual scans) until there is evidence of metastatic disease, because other options have not been available. These patients are excellent candidates for innovative treatments hypothesized to slow the progression of clinical prostate cancer and delay the development of metastatic disease. Preclinical studies of muscadine grape skin (a type of natural supplement) offer evidence that it may extend the time between biochemical recurrence (rising PSA) and development of metastatic disease. While a Phase II study found no significant difference in PSA doubling time between placebo and MPX, there was a signal of benefit in the subgroup analysis of men with the Alanine/Alanine superoxide dismutase 2 (SOD2) genotype that received high dose MPX. It is therefore proposed to test the benefits of high dose MPX in capsule formulation in a randomized, controlled study of men who have failed primary therapy, either radiation, surgery or cryotherapy, as primary treatment for prostate cancer. This study has 2 arms: Arm A: Muscadine Plus Each treatment cycle consists of once daily oral (taken by mouth) dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug. Arm B: Placebo Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug.

The immune system is the cells and organs in the body that recognize and fight infection and cancer. The PROSTVAC vaccine might teach the immune system to find and kill certain prostate cancer cells. Nivolumab (a type of immunotherapy) and ipilimumab (a type of immunotherapy) are drugs that allow the immune system to fight tumors. They might help PROSTVAC work better.

The objective of this study is to test the safety and effectiveness of the combination of PROSTVAC, nivolumab, and ipilimumab for people with castrate resistant prostate cancer and then for other people with prostate cancer.

Patients will be enrolled in one of four cohorts:

Lead-in mCRPC (metastatic castration resistant prostate cancer) Cohort:

PROSTVAC-V (an injection given in the clinic) on week 0 followed by booster injection called PROSTVAC-F on weeks 2, 5 and 8. Nivolumab and ipilimumab will be administered at the same time as the booster injections.

Nivolumab is given intravenously (IV in clinic) at 240 mg over approximately 60 minutes. Ipilimumab is given IV (in clinic) at 1mg/kg over approximately 90m minutes.

Patients will undergo sigmoidoscopies on week 10 and restaging scans on week 12. If there is no disease progression/growth, the option is given to continue treatment every 3 weeks until intolerance or progression.

Cohort A:

PROSTVAC-V on week 0 followed by booster injection called PROSTVAC-F on weeks 2, 5 and 8. Nivolumab will be administered at the same time as the booster injections.

Nivolumab is given IV at 240 mg over approximately 60 minutes.

Patients will undergo prostatectomy on week 10.

Cohort B:

PROSTVAC-V on week 0 followed by booster injection called PROSTVAC-F on weeks 2, 5 and 8. Ipilimumab will be administered at the same time as the booster injections.

Ipilimumab is given IV at 1mg/kg over approximately 90m minutes.

Patients will undergo prostatectomy on week 10.

Cohort C:

PROSTVAC-V on week 0 followed by booster injection called PROSTVAC-F on weeks 2, 5 and 8. Nivolumab and ipilimumab will be administered at the same time as the booster injections.

Nivolumab is given IV at 240 mg over approximately 60 minutes.

Ipilimumab is given IV at 1mg/kg over approximately 90m minutes.

Patients will undergo prostatectomy on week 10.

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 look at patient outcomes when docetaxel (a type of chemotherapy) is started prior to androgen deprivation therapy (ADT) with degarelix (a type of hormonal therapy). This study will look at two drugs, docetaxel and degarelix, which are both FDA approved for the treatment of prostate cancer. Docetaxel is a standard chemotherapy treatment for metastatic prostate cancer. Degarelix is an androgen deprivation therapy (ADT) agent that decreases the amount of testosterone in the body, which helps to fight tumor growth. Usually, docetaxel is given after ADT. This study will look at how your cancer changes when docetaxel is started before ADT. You are being asked to participate in this study because you have metastatic prostate cancer that can be treated with docetaxel and ADT. This study has 1 arm: Docetaxel + Degarelix Docetaxel (Taxotere)) will be given for up to 6 cycles once every 21 days. During the 5th and 6th cycles, degarelix (Firmagon) will be administered on Cycle 5 day 1 and cycle 6 day 8. After cycle 6, degarelix will continue to be given every 28 days for a 5 more doses, for a total of 7 doses.

This is a biomarker (specific cells or mutations in the tumor tissue) preselected, randomized, open-label, multicenter, phase II study in men with metastatic castration resistant prostate cancer (mCRPC). Patients with tumors that have ATM, BRCA1 and/or BRCA2 mutations/deletions/loss of heterozygosity (or loss of the difference in cell types) will be randomized in a 1:1:1 fashion to each arm. Patients with mutations in DNA repair genes including FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A defects will be assigned to Arm IV with single agent olaparib. This study requires tumor tissue to be tested for these mutations, either tissue from a previous biopsy or surgery, or a biopsy to be performed for the study.

Patients will be randomized to one of four arms:

Arm I: Abiraterone (a type of hormonal or anti-androgen therapy) + Prednisone (a steroid)

Abiraterone 1000 mg is taken orally (at home) once daily and prednisone 5 mg is taken orally (at home) twice daily, days 1-28 in 28 day cycles.

Arm II: Olaparib (Lynparza, a type of targeted therapy)

Olaparib 300 mg is taken orally (at home) twice daily for days 1-28 in 28 day cycles.

Arm III: Abiraterone + Prednisone + Olaparib

Abiraterone 1000 mg is taken orally (at home) once daily, prednisone 5 mg is taken orally (at home) twice daily, olaparib 300 mg is taken orally (at home) twice daily for days 1-28 in 28 day cycles.

Arm IV: Olaparib

Olaparib 300 mg is taken orally (at home) twice daily for days 1-28 in 28 day cycles.

The purpose of this study is to determine how patients with metastatic castration-resistant prostate cancer and evidence of a homologous recombination gene deficiency (a particular type of genetic mutation), respond to treatment with rucaparib (Rubraca, a type of targeted therapy) versus treatment with their physician's choice of abiraterone acetate (Zytiga, a type of anti-androgen or hormonal therapy), enzalutamide (Xtandi, a type of anti-androgen or hormonal therapy), or docetaxel (Taxotere, a type of chemotherapy).

Patients will be randomized to one of two arms:

Arm A: Rucaparib only – rucaparib is a drug taken orally (at home) once daily.

Arm B: Physician’s choice of abiraterone acetate, enzalutamide, or docetaxel. Abiraterone acetate and enzalutamide are oral drugs that are taken daily (at home). Docetaxel is a drug given intravenously (IV) once every 3 weeks (in clinic).

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 evaluate the tolerability and safety profile of ASP1948 (a type of immunotherapy) when administered as a single agent and in combination with nivolumab (Opdivo, a type of immunotherapy) in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the activity in the body of ASP1948 when administered as a single agent and in combination with nivolumab and determine the recommended Phase 2 dose of ASP1948 when administered as a single agent and in combination with nivolumab. This study will also evaluate the antitumor effect of ASP1948 when administered as a single agent and in combination with nivolumab. This study has 2 arms: Arm A: ASP1948 monotherapy ASP1948 is given intravenously (IV) at escalating dose levels provided by the treatment team. Arm B: ASP1948 plus nivolumab Combination Therapy ASP1948 will be administered IV in combination with a fixed dose of nivolumab IV every 2 weeks.

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)

This is a multicenter, randomized, controlled, phase 2 clinical trial designed to evaluate the safety and efficacy of I-131-1095 radiotherapy (a type of radiation therapy) in combination with enzalutamide (Xtandi, a type of hormonal therapy) compared to enzalutamide alone in patients with prostate-specific membrane antigen (PSMA)-avid (positive) metastatic castration resistant prostate cancer (mCRPC) who have progressed on abiraterone (Zytiga, a type of hormonal therapy). Patients must be chemotherapy-naive (never had chemotherapy) and must be ineligible or refuse to receive taxane-based chemotherapy at time of study entry. PSMA-avidity will be determined by imaging during screening. Eligible patients meeting the PSMA-avidity criteria will be randomized in a 2:1 ratio to receive either I-131-1095 in combination with enzalutamide (80 subjects) or enzalutamide alone (40 subjects). Patients will be followed for effectiveness and safety during a 12-month period. Patients will be followed for an additional year for safety and survival status. There are 2 arms in this study: Arm A: Enzalutamide alone Enzalutamide will be given orally once daily as prescribed by the physician as standard of care. Arm B: I-131-1095 in combination with enzalutamide I-131-1095 will be administered intravenously (IV) for an initial therapeutic dose, and up to 3 additional dose(s), administered at least 8 weeks apart. Enzalutamide will be given orally once daily as prescribed by the physician as standard of care.

This randomized phase II trial studies how well abiraterone acetate (an anti-androgen or hormonal therapy) and antiandrogen therapy, with or without cabazitaxel (a type of chemotherapy) and prednisone (a type of steroid given with chemotherapy), work in treating patients with castration-resistant prostate cancer previously treated with docetaxel (a type of chemotherapy) that has spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Hormone therapy using abiraterone acetate and antiandrogen therapy may fight prostate cancer by lowering and/or blocking the use of androgens by the tumor cells. Drugs used in chemotherapy, such as cabazitaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving abiraterone acetate and antiandrogen therapy with or without cabazitaxel and prednisone may help kill more tumor cells. This study has 2 arms: Arm A: Abiraterone acetate + prednisone + cabazitaxel Patients receive abiraterone acetate by mouth (oral, taken at home) once daily on days 1-21, prednisone by mouth twice daily on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days (1 cycle = 21 days) in the absence of disease progression or unacceptable side effects. Patients receive cabazitaxel intravenously (IV, given in clinic) over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable side effects. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist (standard hormonal therapy), or surgical castration with bilateral orchiectomy (removal of both testes). Arm B: Abiraterone acetate + prednisone Patients receive abiraterone acetate by mouth (oral, taken at home) once daily on days 1-21, prednisone by mouth twice daily on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days (1 cycle = 21 days) in the absence of disease progression or unacceptable side effects. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist (standard hormonal therapy), or surgical castration with bilateral orchiectomy (removal of both testes).

This study is designed to test experimental bipolar androgen therapy (BAT) as a potential treatment for patients whose cancer has progressed on either enzalutamide or abiraterone. BAT involves testosterone injections that cause testosterone levels in the body to fluctuate. This confuses the cancer cells. Creating this repeated rise and fall in testosterone levels has shown potential to reduce prostate-specific antigen and slow disease progression. For this trial, BAT therapy involves receiving a testosterone injection every 28 days. If and when the disease progresses on BAT, BAT will be stopped and participants will resume the previous hormone therapy (either enzalutamide or abiraterone) that they were on before the trial.

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).

This study compares radiographic progression free survival (rPFS) in men with mCRPC treated with talazoparib (a type of targeted therapy, a PARP inhibitor) plus enzalutamide (Xtandi, a type of hormonal therapy) vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide. This study has 2 arms: Arm 1: Talazoparib plus enzalutamide Talazoparib 0.5 mg taken by mouth once daily plus enzalutamide 160mg taken by mouth once daily Arm 2: Placebo with enzalutamide Placebo taken by mouth once daily plus enzalutamide 160 mg taken by mouth once daily

CCW702 is an investigational immunotherapy for prostate cancer. This is a two-part, first-in-human study to assess the safety and tolerability of CCW702 administered by subcutaneously (SC or SQ) injection to patients with metastatic, castration resistant prostate cancer. In part I, patients will receive increasing dosages of CCW702 with the goal to determine the maximum tolerated dose (MTD) of CCW702. In part II of the study, patients will be given one of two dosing regimens of CCW702 to determine which regimen is most effective. Treatment – all patient will receive CCW702. Dosages will vary and may be adjusted if needed. CCW702 is administered by subcutaneous injection in clinic. Dosing schedule will be provided.

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.

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)

The aim of this research is to find out if the study drug rucaparib (a type of targeted therapy, a PARP inhibitor) leads to lowering of PSA levels in men with metastatic prostate cancer that has not yet been treated with androgen deprivation therapy (also referred to as metastatic hormone sensitive prostate cancer) and who have an inherited mutation in a gene involved in repairing DNA damage. The research will also examine if rucaparib is safe in individuals with metastatic prostate cancer. Prior research studies have shown that drugs like rucaparib can be of benefit to patients with advanced metastatic prostate cancer who are resistant to androgen deprivation therapy AND who carry a mutation in a DNA repair gene. We are studying if rucaparib will be an effective treatment for these patients earlier in their treatment course (for example, prior to the start of medicines that lower testosterone level). It is unknown whether rucaparib will have the same benefit in men with metastatic prostate cancer carrying a mutation in a DNA repair gene, prior to the use of medicines that lower your testosterone level. This study has 1 arm: Rucaparib 600mg by mouth (orally) twice daily, continuous dosing.

This study is a large, prospective, pragmatic, controlled comparison of patient-centered outcomes between parallel cohorts of men with prostate cancer treated simultaneously at proton therapy (a type of radiation therapy) facilities and at geographically similar conventional (photon-based) radiation facilities using intensity-modulated radiation therapy (IMRT) techniques. All interventions will be standard of care (SOC) radiation strategies using either IMRT or proton therapy. All patient-reported quality of life (QOL), patient-scored and patient-reported toxicity, and disease control assessments will be SOC. Participants will also complete pretreatment surveys regarding demographic data, personal treatment goals, factors affecting treatment decision-making, and sources of information used in treatment selection. There is no treatment given directly as part of this study; radiation will be given per standard of care (SOC) at the participating site you are being treated at.

People with prostate cancer usually have their cancer imaged with a CT scan and bone scan. They then have their prostate gland removed. Researchers want to test a scan that might predict if prostate cancer will return after this surgery. Participants will have a radiotracer injected into a vein (IV). They will have a PET/CT scan of their whole body 60-90 minutes later. During the scan, they will lie on their back and stay still. Within 60 days after the scan, participants will have surgery. This will remove the prostate gland and lymph nodes around it. Some tissue will be used for genetic testing. If the PET/CT scan suggests the cancer has spread, participants may need to have another biopsy within 60 days after the scan. After surgery, participants will have follow-up visits for 5 years. They will have 5 visits the first year and 2 the second. Then they will have visits once a year. If participants cancer returns, they will have repeat PET/CT scans. This is an imaging only study, there is no treatment given.

The primary purpose of this study is to evaluate the tolerability and safety profile of ASP1951 (a type of immunotherapy) when administered as a single agent and in combination with pembrolizumab (Keytruda, a type of immunotherapy) in participants with locally advanced (unresectable) or metastatic solid tumors; characterize how ASP1951 works in the body when administered as a single agent and in combination with pembrolizumab; and determine the recommended dose of ASP1951 when administered as a single agent and in combination with pembrolizumab. This study will also evaluate the anti-tumor effect of ASP1951 when administered as a single agent and in combination with pembrolizumab. This study has 2 arms: Arm A: Monotherapy with ASP1951 ASP1951 will be given intravenously (IV) in clinic. Dose and dosing schedule will be provided by treatment team. Arm B: Combination therapy with ASP1951 + pembrolizumab ASP1951 and pembrolizumab are both given intravenously (IV) in clinic. Dose and dosing schedule will be provided by treatment team.

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.

The purpose of this study is to evaluate whether Fuzuloparib (a type of targeted therapy) plus AA-P (Zytiga, a type of hormonal therapy) is superior to placebo plus AA-P as first-line treatment by assessment of radiographic (CT, bone scan imaging) progression-free survival in mCRPC subjects with or without DNA damage repair deficiencies (requires. This study has 2 treatment arms: Arm A: Fuzuloparib plus AA-P Patient will receive Fuzuloparib 150 mg (3 x 50 mg capsules) by mouth (orally or PO) twice daily plus Abiraterone acetate 1000 mg (4 x 250 mg tablets) by mouth once daily plus Prednisone 5 mg by mouth twice daily (1 x 5 mg tablet) Arm B: Placebo plus AA-P Patient will receive Placebo 3 capsules by mouth (orally or PO) twice daily plus Abiraterone acetate 1000 mg (4 x 250 mg tablets) by mouth once daily plus Prednisone 5 mg by mouth twice daily (1 x 5 mg tablet)

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 purpose of this study is to evaluate the safety and tolerability and preliminary antitumor activity of MGC018 (a type of targeted therapy) administered alone and in combination with MGA012 (a type of immunotherapy) in patients with advanced solid tumors, including metastatic castrate-resistant prostate cancer (mCRPC). This study has 2 arms: Arm A: MGC018 Monotherapy Specific dose and dosing schedule will be provided by your treating physician. Arm B: MGC018 plus MGA012 Specific dose and dosing schedule will be provided by your treating physician.

This is a Phase 1 open-label, dose escalation and dose expansion study of CPI-006, a humanized monoclonal antibody (a type of targeted therapy) in adult subjects with select advanced cancers. CPI-006 will be evaluated as a single agent (monotherapy or by itself), in combination with ciforadenant (a type of targeted therapy), in combination with pembrolizumab (Keytruda, a type of immunotherapy), and in combination with both ciforadenant and pembrolizumab. This study has multiple treatment arms. All subjects will receive CPI-006. Dose levels will be provided by your treatment team. Some subjects will also receive either ciforadenant or pembrolizumab, or both. Dose levels will be provided by your treatment team. CPI-006 and pembrolizumab are given intravenously (IV) in clinic once every 21 days. Ciforadenant is taken by mouth (orally or PO) twice daily.

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.

The purpose of this research study is to evaluate safety, pharmacokinetics (how the drug moves through your body), pharmacodynamics (how the drug works in your body) and preliminary effectiveness of the investigational drug PLX2853 (a type of targeted therapy) in subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC). This study has 2 treatment arms: Arm A: PLX2853 + Abiraterone Acetate + Prednisone Dose level and dosing schedule will be provided by your treatment team. All treatment drugs are taken by mouth (orally or PO). Arm B: PLX2853 + Olaparib Dose level and dosing schedule will be provided by your treatment team. All treatment drugs are taken by mouth (orally or PO).