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.

Phase 2 open-label, single-arm clinical trial evaluating the efficacy and safety of neoadjuvant olaparib (Lynparza, a type of targeted therapy) + LHRH agonist (a type of hormonal therapy) administered for 6 months prior to radical prostatectomy (RP, surgery) in men with unfavorable intermediate-risk or high-risk localized prostate cancer. All patients must have confirmed germline or somatic BRCA1/2 gene mutation. Germline and somatic mutation testing will be performed as part of commercially available CLIA assays and will be validated on a uniform platform centrally for all patients. All subjects will receive treatment: Olaparib + LHRH agonist 300 mg of olaparib taken orally (by mouth, PO) twice a day for 6 cycles (approximately 6 months). There are 30 days in a cycle. Olaparib will be taken with an LHRH agonist (leuprolide, triptorelin, or goserlin). This choice of therapy will be taken for a total of 180 days per institutional standards. After 6 cycles of neoadjuvant therapy, patients will undergo a radical prostatectomy (RP). After RP, patients will be followed for testosterone recovery and PSA progression.

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 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 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 phase II trial tests whether relugolix (a type of hormonal therapy) and radiation therapy works to shrink tumors in patients with prostate cancer that has spread in a limited way to 1 to 5 other parts of the body (oligometastatic). Testosterone can cause the growth of prostate cancer cells. Relugolix lowers the amount of testosterone made by the body. This may help stop the growth of tumor cells that need testosterone to grow. Giving relugolix with radiation therapy may help lower the chance of prostate cancer growing or spreading. This study has 2 arms: Arm A: relugolix + SABR (Stereotactic Body Radiation Therapy, SBRT) Patients receive relugolix PO (by mouth, orally) once daily (QD) on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Arm B: placebo + SABR Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.

This phase III trial compares stereotactic body radiation therapy (SBRT), (five treatments over two weeks using a higher dose per treatment) to usual radiation therapy (20 to 45 treatments over 4 to 9 weeks) for the treatment of high-risk prostate cancer. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period of time. This trial is evaluating if shorter duration radiation prevents cancer from coming back as well as the usual radiation treatment. This study has 2 arms: Arm A: Stereotactic Body Radiation Therapy (SBRT) Patients undergo SBRT for a total of 5 treatments over 2 weeks. Arm B: External Beam Radiation Therapy (EBRT) Patients undergo EBRT for 20 to 45 treatments over 4 to 9 weeks.

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 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.

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.

This is a phase 3, randomized, open-label study of opevesostat (a type of targeted hormonal therapy) compared to alternative abiraterone acetate (Zytiga, a type of hormonal therapy) or enzalutamide (Xtandi, a type of hormonal therapy) in participants with metastatic castration-resistant prostate cancer (mCRPC) in participants with mCRPC previously treated with next-generation hormonal agent (NHA, second line hormonal theapy) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior in certain participants. This study has 2 arms: Arm A: Opevesostat Participants receive opevesostat 5 mg tablets by mouth (po, orally) twice daily plus dexamethasone (a type of steroid) 1.5 mg tablets by mouth once daily and fludrocortisone acetate (a type of steroid) 0.1 mg tablet by mouth until disease progression. Arm B: Abiraterone Acetate or Enzalutamide Participants receive abiraterone 1000 mg tablets by mouth once daily plus prednisone 5 mg tablets by mouth twice daily, OR enzalutamide 160 mg tablets by mouth once daily.

The goal of this study is to test the preliminary effectiveness of a home-based exercise training (ET) intervention to improve exercise capacity among prostate cancer (PC) patients compared to controls receiving healthy living education (HLE) at 12 weeks. This is a supportive care study. This study has 1 arm for patients with prostate cancer: Arm A: Exercise Training Intervention The exercise program (ET) is tailored to each participant depending on his initial functional capacity, cardiorespiratory fitness and strength, to achieve moderate to vigorous physical activity. The behavioral ET and HLE interventions will be delivered over 12 weeks. Before starting the study, men will be asked to attend one in-person small group orientation to provide an overview of the intervention, familiarize them with web-based and smartphone applications or hard copy manuals for delivery of intervention content, exercise logs, resistance bands, and equipment for strength training.

This phase III trial tests whether high-dose vitamin D works in treating androgen-deprivation therapy (ADT, hormone therapy)-induced bone loss in patients with prostate cancer who are undergoing ADT. Vitamins are substances that the body needs to grow and develop normally. Vitamin D helps the body absorb calcium. Calcium is one of the main building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis or rickets. This trial may help researcher determine if high-dose vitamin D helps keep bones strong, lowers number of falls, and lessens fatigue in men getting androgen-deprivation therapy. This is a supportive care study. This study has 2 arms: Arm A: High does vitamin D (HDVD) Patients receive HDVD orally (PO, by mouth) throughout the study. Patients also undergo collection of blood and DEXA scan on study. Arm B: Placebo Patients receive placebo PO throughout the study. Patients also undergo collection of blood and DEXA scan on study.

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.

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.

The purpose of this study is to assess the effectiveness and safety of opevesostat (a type of targeted therapy) plus hormone replacement therapy (HRT) compared to alternative abiraterone acetate (a type of hormonal therapy) or enzalutamide (a type of hormonal therapy) in participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The study hypothesis is that opevesostat is superior to the alternative abiraterone acetate or enzalutamide. This study has 2 arms: Arm A: hormone replacement therapy (HRT)+ opevesostat Participants receive opevesostat 5 mg tablets by mouth (PO, orally) twice daily (BID) plus dexamethasone (a steroid) 1.5 mg tablets by mouth and fludrocortisone acetate (a steroid) 0.1 mg tablets by mouth once daily (QD) continuously until disease progression. Hydrocortisone (a steroid) 100 mg (oral or intramuscular injection [IM]) will also be provided to participants for use as rescue medication. Arm B: Alternative next generation hormonal agent (NHA) Participants receive Abiraterone 1000 mg tablets by mouth QD plus Prednisone 5 mg tablets by mouth BID OR Enzalutamide 160 mg tablets by mouth QD until disease progression.

This is a prospective, open-label Phase 3 study to evaluate copper Cu 64 PSMA I&T injection (a type of contrast to help detect prostate cancer) for PET/CT imaging in patients with newly diagnosed unfavorable intermediate high-risk, high-risk or very high-risk prostate cancer. The purpose of this study is to evaluate the safety, biodistribution (how the contrast spreads throughout the body), and image quality of Copper Cu64 PSMA I&T Injection to detect metastatic prostate cancer in PET imaging. This is not a treatment study; it is an imaging study only. All subjects will receive diagnostic imaging with copper Cu 64 PSMA I&T injected intravenously (IV) for staging of prostate cancer.

The PRELUDE trial is a prospective, non-randomized, single-arm, phase 2 interventional study to assess the oncological outcomes after 2 cycles of Lu-177-PSMA-617 (Pluvicto, a type of radiation treatment) administered at 6-week intervals before prostatectomy in patients with high risk localized prostate cancer. All patients will receive 2 cycles of Lu-177-PSMA-617 (Pluvicto) administered once every 6 weeks.

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)

The purpose of this study is to evaluate the effectiveness and safety of lutetium (177Lu) vipivotide tetraxetan (AAA617, a type of radiation treatment) in participants with oligometastatic prostate cancer (OMPC) progressing after definitive therapy to their primary tumor. The data generated from this study will provide evidence for the treatment of AAA617 in early-stage prostate cancer patients to control recurrent tumor from progressing to fatal metastatic disease while preserving quality of life by delaying treatment with androgen deprivation therapy (ADT). This study has 2 arms: Arm A: lutetium (177Lu) vipivotide tetraxetan (AAA617) All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by a dose of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 4 cycles. Arm B: No Intervention, observation only (watchful waiting) All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by observation only.

This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy or ADT). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide (Nubeqa) to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (like testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading. This study has 3 arms: Arm A: Radiation alone Patients undergo RT using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity. Arm B: Radiation + ADT Patients undergo RT as Arm A. Patients also receive ADT consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days. Arm C: Radiation + ADT + darolutamide Patients receive RT and ADT as in Arm II. Patients also receive darolutamide PO BID on days 1-90. Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

The current standard treatment of prostate cancer is either surgery or radiation. Typically, this includes either the removal or radiation of the whole prostate gland. Many people now seek out focal therapy options to decrease the side effects of treatment. Until now, several forms of physical destruction with heat (thermal ablation), cold (cryotherapy), sound waves (HIFU), laser (FLA), and electrical energy (IRE). A new type of radiation (SBRT) may be an effective way to cure men of early-stage prostate cancer with fewer side effects than standard treatments. The objective of this study is to see how people with untreated localized prostate cancer will respond to focal therapy with SBRT. All participants will receive radiation therapy with SBRT. Participants will undergo screening including blood tests, an MRI, a PSMA PET/CT (18F-DCFPyL), and a biopsy. Small, non-radioactive, gold seeds about the size of a grain of rice will be placed in and/or around the tumor to help target the radiation treatment. Radiation (SBRT) will occur in 2 separate sessions about 1 week apart. No sedation is used, these sessions are painless. Each session will take about 1-2 hours. Participants can go home afterwards. Follow-up will continue for 2 years with repeat scans (MRI and PSMA PET/CT) and blood (PSA) tests. After two years, a biopsy will be done to understand the impact of this new treatment on prostate cancer.

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.

Prostate cancer may return after treatment in 30,000 to 50,000 people each year. There is no clear best way to treat these people. Better treatments are needed. This study will test enzalutamide (Xtandi, a type of hormonal therapy), both alone and combined with M9241 (a type of immunotherapy) in people with prostate cancer that returned after treatment, to determine if the combination of enzalutamide and immunotherapy (M9241) keeps PSA suppressed longer compared to enzalutamide alone. This study has 2 arms: Arm A: Enzalutamide Enzalutamide at 160 mg once daily by mouth (orally, PO) on every day of the cycle (1 cycle = 28 days). Arm B: Enzalutamide + M9241 Enzalutamide at 160 mg once daily by mouth on every day of the cycle PLUS M9241 at 12.0 microgram/kg by subcutaneous injection (sc, sq) once every 28 days.

The purpose of this research study is to compare the side effects, both good and/or bad, of using the standard of care treatment, hormonal therapy, and Stereotactic Ablative Radiation (SABR, a type of radiation therapy) to the metastatic prostate cancer lesions, compared to standard of care and addition of 6-months of niraparib/abiraterone acetate (Akeega, a type of targeted + hormonal therapy) combination pills and prednisone (a type of steroid) for participants with recurrent metastatic prostate cancer. This study has 2 treatment arms: Arm A: Androgen deprivation therapy + Stereotactic ablative radiation All ADT is provided as best prescribed for patient per their medical oncologist. Arm B: Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate Patients will receive niraparib/abiraterone acetate for 6 months. Dose level and schedule will be provided by the treatment team.

This research is being done to determine if we can improve the outcome of prostate cancer patients who have progressed after primary treatment - surgery or local radiation to the prostate - and have three or fewer bone or soft tissue metastases. This study will compare the side effects, good and/or bad, of using the standard of care treatment (systemic therapy + primary prostate radiation) compared to standard of care treatment plus stereotactic ablative radiation therapy (SABR) to metastatic lesions for prostate patients. The researchers are also trying to learn if the addition of SABR will affect recurrence rates. This study has 2 arms: Arm A: Best systemic therapy (BST) + primary prostate radiation (XRT) All systemic therapy is provided as best prescribed for patient per their medical oncologist. Arm B: BST + XRT + SABR metastasis-directed therapy (MDT)

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.

Approximately one million transrectal prostate biopsies are performed annually in the U.S., and the risk of post- biopsy infection is increasing due to greater antibiotic resistance of rectal flora. Preliminary data demonstrates that a transperineal MRI-targeted biopsy approach under local anesthesia compared to the standard practice transrectal MRI-targeted prostate biopsy has a much lower risk of infection, comparable pain/discomfort and may improve detection of prostate cancer.

Traditional radical prostatectomy is the most popular treatment for clinically significant prostate cancer, however significant risks including urinary incontinence, erectile dysfunction, penile shortening, penile curvature/ deformation (Peyronie's disease), and inguinal hernia, are common. Pelvic fascia-sparing radical prostatectomy is a new surgical technique that may preserve fascial support structures, arterial supply to the penis, and nerves that are severed and resected during conventional radical prostatectomy. This study will enroll adult men undergoing radical prostatectomy for clinically localized prostate cancer. Subjects will be randomized to receive either radical prostatectomy or pelvic fascia-sparing radical prostatectomy. Investigators will compare cancer control and health-related quality of life outcomes through patient questionnaires and medical record review. The investigators hypothesize that pelvic fascia-sparing radical prostatectomy will have similar cancer control (primary outcome) and sexual function outcomes; and significantly A novel, posterior approach to radical prostatectomy that preserves the dorsal vascular complex, nerves and fascial support structures that overlie the anterior prostate. These structures are disrupted and removed during conventional radical prostatectomy. better urinary function, penile shortening/deformity and inguinal hernia risks as compared to radical prostatectomy. This study has 2 arms: Arm A: Robot-assisted radical prostatectomy (RP) The conventional robotic-assisted radical prostatectomy is the gold standard approach to prostate cancer surgery. Arm B: Pelvic fascia-sparing robot-assisted radical prostatectomy (PFS-RP)

The purpose of this study is to establish the safety and preliminary antitumor activity of ORIC-944 (a type of targeted therapy) as a single agent and in combinations with hormonal therapy in patients with metastatic prostate cancer. ORIC-944 is a potent, highly selective, allosteric, orally bioavailable, small molecule inhibitor of PRC2.

The goal of this study is to evaluate the safety and tolerability of AMG 509 (Xaluritamiga, a type of targeted immunotherapy) in adult participants, and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). All participants will receive treatment with AMG 509 administered as an intravenous (IV) infusion or as a subcutaneous (SC) injection. Treatment team will provide details on dose level and frequency.

This study is a randomized, open-label, Phase 2 study. The study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT, a type of hormonal therapy). ARAT includes abiraterone, enzalutamide, or apalutamide. Participants may have received up to 1 prior taxane-containing regimen, but no other chemotherapy agents. The study will assess effectiveness and tolerability of vobramitamab duocarmazine (a type of targeted therapy) at two different dose levels. All patients will receive treatment with vobramitamab duocarmazine at either 2.0 or 2.7 mg/kg given intravenously (IV) once every 4 weeks.

The goal of this study is to determine the feasibility and acceptability of recruiting a sample of medically underserved prostate cancer patients undergoing treatment with Androgen Deprivation Therapy (ADT, hormone therapy) to a remotely delivered exercise intervention (like a home-based program). This is a supportive care study. This study has 1 arm. Arm A: Behavioral exercise training (BET) to introduce behavioral skills for adopting an exercise program The BET intervention will be delivered and refined over 12 weeks. The protocol aim is to enroll men from the same representative groups of underserved men in groups of 5-10, to foster social support and group cohesion. The BET intervention will introduce and refine concept of exercise and cardiovascular health by initiating walking or cycling and provide behavioral counseling sessions to foster support for adoption and maintenance of exercise, and to troubleshoot barriers. During the first two weeks, the study team will meet with participants twice per week (virtually) to introduce the intervention, familiarize men with the exercise program, exercise logs, resistance bands for strength training. Contact will drop to once per week during weeks 3-8 (total=10 contacts in weeks 1-8). Behavioral counseling will be delivered for 30-40 minutes prior to 20-30 mins of an individual or group-based strength training class.

A Phase 1/2 study to evaluate the safety and effectiveness of ARV-766 (a type of targeted therapy) given by mouth in men with metastatic castration-resistant prostate cancer who have progressed on prior approved systemic therapies. All patients will receive treatment with ARV-766 taken orally (by mouth, po) once or twice daily for 28 day cycles. Dose level and dosing schedule will be provided by the treatment team.

This study evaluates the effectiveness, anti-tumor effect, and immune effect of neoadjuvant enoblituzumab (a type of targeted therapy) given before radical prostatectomy. Patients will be randomized to enoblituzumab for a total of 12 weeks beginning 84 days before radical prostatectomy in men with high-risk localized prostate cancer, or to standard of care. This study has 2 treatment arms: Arm A: Enoblituzumab Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab at a dose of 15mg/kg IV (intravenously) every 2 weeks for 12 weeks, followed by a radical prostatectomy on day 84, with follow-up visits 30 days, 90 days, 6 months, and 9 months post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy. Arm B: Standard of Care Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.

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 intention of the study is to demonstrate superiority of Saruparib (a type of targeted therapy) + physician's choice of secondary hormonal therapy versus placebo + physician's choice of secondary hormonal therapy assessed by radiographic and progression free survival in patients with metastatic castration sensitive prostate cancer. This study has 2 arms: Arm A: Saruparib + Physician's Choice of secondary hormonal therapy. Dosing and dosing schedule to be provided by treatment site. Arm B: Placebo + Physician's Choice of secondary hormonal therapy. Dosing and dosing schedule to be provided by treatment site.

Multicenter, open-label dose-escalation Phase I/II clinical study, designed to evaluate the safety, tolerability, activity, anti-tumor activity, and effectiveness of TT-10 (a type of targeted therapy) in subjects diagnosed with advanced Renal cell cancer (RCC) and castrate resistant prostate cancer (CRPC) who have failed or are not eligible for standard of care treatment. All patients will receive treatment with TT-10 orally administered (by mouth, po) twice daily starting at 10 mg and will be increased to 200 mg (additional dose levels maybe explored, if appropriate).

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 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 goal of this clinical trial is to examine the safety and effectiveness of ONC-392 (a type of immunotherapy) in combination with lutetium Lu 177 vipivotide tetraxetan (Pluvicto, a type of radiation therapy) in metastatic castration resistant prostate cancer patient who have disease progressed on hormonal therapy. The main questions it aims to answer are (1) whether it is safe to combine ONC-392 with lutetium Lu 177 vipivotide tetraxetan, (2) whether the combination increases the radiographic progression free survival (rPFS). This study has 2 arms: Arm A: ONC-392 PLUS lutetium Lu 177 vipivotide tetraxetan Participants receive ONC-392 via intravenous (IV) infusion, for up to 9 doses, PLUS lutetium Lu 177 vipivotide tetraxetan via IV infusion, once every 6 weeks for up to 6 doses. Arm B: lutetium Lu 177 vipivotide tetraxetan Participants receive lutetium Lu 177 vipivotide tetraxetan via IV infusion, once every 6 weeks for up to 6 doses.

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.

NUV-868-01 (a type of targeted therapy) is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in patients with advanced solid tumors. The Phase 1 portions include patients with advanced solid tumors and are designed to determine the safety and the dose(s) of NUV-868 to be used as monotherapy (single therapy) and in combination with olaparib (Lynparza, a type of targeted therapy) or enzalutamide (Xtandi, a type of hormonal therapy) for the Phase 2 portion. In Phase 2, NUV-868 in combination with olaparib or enzalutamide will be given to determine the safety and effectiveness of these study treatments. This study has 4 possible treatment arms: Arm A: NUV-868 alone NUV-868 will be administered orally (by mouth, po) at escalating dose levels to be provided by the treatment team. Arm B: NUV-868 + Olaparib NUV-868 will be administered orally at escalating dose levels in combination with olaparib 300 mg administered orally twice daily throughout a 28 day cycle. Arm C: NUV-868 + Enzalutamide NUV-868 will be administered orally at escalating dose levels in combination with enzalutamide 160 mg administered orally daily throughout a 28 day cycle. Arm D: Enzalutamide Monotherapy Enzalutamide 160 mg will be administered orally once daily.

The objective of the Phase 1 part of the clinical trial is to verify safety, tolerability, and maximum tolerated dose of [177Lu]Ludotadipep (a type of targeted radiation therapy) dose for use in the Phase 2 part of the trial. The objective of the Phase 2 part of the trial is to evaluate safety and effectiveness for repeated administration of the recommended [177Lu]Ludotadipep. All subjects will receive treatment. Phase I: Patients will receive a single dose of [177Lu]Ludotadipep intravenously (IV) Phase II: Patients will receive a dose of [177Lu]Ludotadipep intravenously every 8 weeks (4 to 6 times).

Researchers are looking for a better way to treat men at high-risk of biochemical recurrence (BCR) of prostate cancer. BCR means that in men who had prostate cancer and were treated by either surgery and/ or radiation therapy, the blood level of a specific protein called PSA rises. PSA is a marker of prostate cancer cells activity. The PSA increase means that the cancer has come back even though conventional imaging such as computed tomography (CT) scans, magnetic resonance imaging (MRI) and bone scans does not show any lesion of prostate cancer. Recently a more sensitive imaging method called prostate-specific membrane antigen [PSMA] positron emission tomography [PET]) /computed tomography [CT]) scan may identify prostate cancer lesions not detectable by conventional imaging. Men with BCR have a higher risk of their cancer spreading to other parts of the body, particularly when PSA levels raised to a certain limit within a short period of time after local therapies. Once the cancer spreads to other parts of the body, it can become even harder to treat. In men with prostate cancer, male sex hormones (also called androgens) like testosterone can help the cancer grow and spread. To reduce androgens levels in these patients, there are treatments that block androgens production in the body called androgen deprivation therapy (ADT). ADT is often used to stop prostate cancer. Another way to stop prostate cancer growth and spread is to block the action of androgen receptors on prostate cancer cells called androgen receptor inhibitors (ARIs). The new generation ARIs including darolutamide can block the action of androgens receptors and are available for the treatment of prostate cancer in addition to ADT. It is already known that men with prostate cancer benefit from these treatments. The main objective of this study is to learn if the combination of darolutamide and ADT prolongs the time that the participants live without their cancer getting worse, or to death due to any cause, compared to placebo (which is a treatment that looks like a medicine but does not have any medicine in it) and ADT given for a pre-specified duration of 24 months. This study has 2 treatment arms: Arm A: Darolutamide + ADT Participants will receive darolutamide plus ADT twice daily with food for 24 months. Arm B: Placebo + ADT Participants will receive Placebo plus ADT twice daily with food for 24 months.

This trial compares less intense hormone therapy and radiation therapy to standard of care hormone therapy and radiation therapy in treating patients with high risk prostate cancer and a low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to standard of care hormone therapy and radiation therapy in patients with high risk prostate cancer and a high gene risk score. Abiraterone acetate (Zytiga, a type of hormonal therapy) may help fight prostate cancer by lowering the amount of testosterone made by the body. Apalutamide (Erleada, a type of hormonal therapy) may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the standard of care 24 month hormone therapy treatment in patients with a low gene risk score. Adding abiraterone acetate and apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with a high gene risk score. This study has 3 treatment arms: Arm A: Standard of care radiation (RT) + androgen deprivation therapy (ADT) for 24 months (De-Intensification) Patients undergo RT over 4-9 weeks and receive ADT for 24 months in the absence of disease progression or unacceptable toxicity. Arm B: RT + ADT for 12 months (De-Intensification) Patients undergo RT over 4-9 weeks and receive ADT for 12 months in the absence of disease progression or unacceptable toxicity. Arm C: RT + ADT + Apalutamide + Abiraterone with Prednisone (Intensification) Patients undergo radiation therapy over 4-9 weeks and receive ADT (for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide, abiraterone acetate and prednisone by mouth (PO or orally) once per day (QD). Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity.

Asymptomatic patients with metastatic castrate resistant prostate cancer (mCRPC) without pain due to prostate cancer will be treated on an open label study to evaluate effectiveness of sequential treatment with the combination of difluoromethylornithine (DFMO, Eflornithine, Vaniqa, a type of targeted therapy) and high dose testosterone (a type of hormonal therapy) in sequence with enzalutamide (Xtandi, a type of hormonal therapy) to improve outcomes. All subjects will receive treatment. Repeat Sequential DFMO and High dose Testosterone in Sequence with Enzalutamide: Eligible patients will receive DFMO alone at 1000 mg PO (by mouth) twice daily (bid) on days 1-7 of each cycle, followed by 56 days of combined testosterone cypionate 400 mg intramuscular injection (IM) on day 8 and day 36, AND DFMO (1000 mg PO bid) on days 8-63 of cycle, followed by 56 days of enzalutamide at 160 mg PO once daily on days 64-119.

Prostate cancer is one of most common cancers in America, affecting 1 in 6 men. External beam radiation therapy is one of the common methods to treat prostate cancer. Although radiotherapy is effective, side effects to the nearby normal organs limit the therapeutic ratio. Those side effects are usually associated with the radiation damage of the normal tissue surrounding prostate. Both effectiveness and the side effects of radiation treatment are often assessed after the whole course of radiotherapy, which makes early intervention difficult. The current research project is a feasibility study of utilizing advanced magnetic resonance imaging (MRI) techniques to assess radiotherapy treatment response of prostate cancer during and right after radiotherapy. Many advanced MRI techniques have been used in radiology departments for diagnostic purpose. This research project will study the feasibility of using advanced MRI sequences to monitor tissue response during and after radiotherapy. The tissue changes revealed from MRI can provide physicians early information on possible tumor recurrence and normal tissue toxicity, therefore, early intervention may be possible to spare normal tissue and cure the patient. The project is designed to combine several different advanced MRI imaging techniques systematically to study tissue changes during radiotherapy, which has not been done elsewhere to date. Another important goal of this research project is to study the feasibility of associating functional MRI with radiation treatment dose distribution. Tissue response during radiation treatment depends on dose. The functional MRI can provide more information than simple anatomic information. Mapping the functional MRI spatially and associating them with 3D dose distribution in radiation treatment planning system is one important step to assess the relationship between radiation treatment and tissue changes due to the radiation. There is no treatment provided in this study. MRI imaging in done with standard radiation treatment

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.