Prostate Cancer Trials

This study is designed to determine the safety and tolerability of Entinostat (a type of targeted therapy) with Enzalutamide (Xtandi, a type of hormonal therapy) for treatment of patients with castration-resistant prostate cancer. There will be two dose levels of Entinostat in combination with same dose of Enzalutamide. This study has 1 arm with multiple dose levels: Entinostat Dose level 1: 3mg taken orally (PO) weekly. Dose level 2: 5mg taken orally (PO) weekly. Enzalutamide Dose level 1: 160 mg taken orally (PO) daily. Dose level 2: 160 mg taken orally (PO) daily. Entinostat is formulated for oral administration. A food effect is evident for entinostat; exposure is significantly reduced when entinostat is administered with a high fat meal. Accordingly, entinostat is to be administered on an empty stomach, at least 1 hour before and 2 hours after a meal. Entinostat tablets should not be split, crushed, or chewed.

This is a non-randomized multi-center Phase 1b/2a dose escalation and dose expansion study testing DKN-01 (a type of targeted therapy) as monotherapy or in combination with docetaxel (Taxotere, a type of chemotherapy) in metastatic castration-resistant prostate cancer. Patients need to be biomarker positive (Dickkopf-1 [DKK1]) either in plasma or biopsy. Other biopsies for correlative studies are encouraged but not mandatory. Treatment – this study has 2 treatment arms. *multiple dose levels of DKN-01 will be tested and dose may be adjusted if needed. DKN-01 monotherapy: DKN-01 is given intravenously (IV) in clinic on days 1 and 15 of each 28-day cycle. DKN-01 + docetaxel: DKN-01 is given intravenously (IV) in clinic on days 1 and 15 of each 21-day cycles + docetaxel 75 mg/m2 given IV in clinic on day 1 of every 3 weeks of each 21-day cycle.

Current conventional prostate cancer (PCa) imaging modalities (computed tomography or CT, bone scan, magnetic resonance imaging or MRI, ultrasound) have limited accuracy in the initial staging and for determining prognosis of PCa. Prostate-specific membrane antigen (PSMA) is a cell surface antigen which is highly expressed in PCa and correlates with prognostic factors such as Gleason score. High PSMA expression in prostate tumor has been significantly associated with lethality of disease, allowing specific identification of tumors most in need of treatment. Combined PET and computed tomography (PET-CT) imaging using small molecules targeting PSMA-expressing cells have been developed and tested clinically, and have shown superiority when compared with conventional imaging. An added advantage of PET compared to MRI is the ability to identify both distant metastatic disease as well as intraprostatic disease with one imaging modality. In realization of the toxicity of current therapies, there is substantial interest throughout the urologic oncology community in utilizing focal therapy to mitigate such toxicities. The rationale for focal therapy is based upon the recognition that whole gland treatment is associated with unacceptable toxicity rates. Planning studies have shown that focal brachytherapy (a type of radiation therapy) is feasible and results in significant reductions of dose to surrounding tissue. In a historic cohort of patients treated at Johns Hopkins, the investigators have demonstrated that a modest reduction in dose results in clinically meaningful reductions in urinary toxicity. Al-Qaiseh et al. found that focal plans resulted in >50% reductions in dose to urethra and rectum. However, focal plans were highly sensitive to radioactive seed positioning errors, and focal targeting made seed positioning more critical. This highlights the key utility and importance of the investigators' iRUF system (integrated Registered Fluoroscopy and Ultrasound) in delivering focal therapy. This study will test the combination of PSMA-imaging with iRUF dynamic dosimetry to treat prostate cancer with a focal approach.

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.

The purpose of this study is to assess the effectiveness and safety of the combination of olaparib (Lynparza, a type of targeted therapy, a PARP inhibitor) and pembrolizumab (Keytruda, a type of immunotherapy) in the treatment of participants with mCRPC who have failed to respond to either abiraterone acetate (Zytiga, a type of hormonal therapy) or enzalutamide (Xtandi, a type of hormonal therapy), but not both, and to chemotherapy. The primary study hypotheses are that the combination of pembrolizumab plus olaparib is superior to abiraterone acetate or enzalutamide with respect to overall survival and radiographic progression-free survival (meaning the cancer can not be seen on scans/imaging like CT scans or bone scans). The study has 2 treatment arms: Arm A: Pembrolizumab + Olaparib Participants receive olaparib 600 mg (as two 150 mg oral tablets taken twice daily) continuously until progression PLUS on Day 1 of each 21-day cycle, pembrolizumab 200 mg is given in clinic by intravenous (IV) infusion for up to 35 cycles (approximately 2 years). Arm B: Abiraterone + Prednisone or Enzalutamide Participants receive abiraterone acetate (participants previously treated with enzalutamide) 1000 mg (as two 500 mg or four 250 mg oral tablets taken once daily) PLUS prednisone 10 mg (as one 5 mg tablet taken twice daily) until progression OR participants receive enzalutamide (participants previously treated with abiraterone acetate) 160 mg (as four 40 mg oral tablets or capsules taken once daily) until progression.

This is a phase 2 study that is testing a higher dosage of radiation for localized prostate cancer based on recent studies indicating that prostate tumors would respond better when treated with higher doses of radiation. Normally, radiation is given at 1.8–2.0 Gy. However, participants in this trial will be treated with an experimental regimen, based on new research concerning prostate cancer cell biology, of 3.6 Gy per day for a total of 57.6 Gy.

This phase I trial studies the side effects and best dose of PI3Kbeta inhibitor AZD8186 (a type of targeted therapy) when given together with docetaxel (Taxotere, a type of chemotherapy) in treating patients with solid tumors, including prostate cancer, with PTEN or PIK3CB mutations that have spread to other places in the body (metastatic) or cannot be removed by surgery. PI3Kbeta inhibitor AZD8186 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, 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 PI3Kbeta inhibitor AZD8186 and docetaxel may work better in treating patients with solid tumors. Treatment – this study has 1 arm. Docetaxel + AZD8186 Patients receive docetaxel intravenously (IV) in clinic over 1 hour on day 1 + PI3Kbeta inhibitor AZD8186 by mouth (orally or PO) twice daily for 5 days each week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

This study will assess the effectiveness and safety of pembrolizumab (Keytruda, a type of immunotherapy) plus enzalutamide (Xtandi, a type of hormonal therapy) plus ADT (hormonal therapy) versus placebo plus enzalutamide plus ADT in participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS, the time it takes to see the cancer on imaging scans like CT or bone scans) 2) overall survival (OS, how long you live overall, even if you do develop cancer that can be seen on imaging scans). Treatment – this study has 2 arms. Pembrolizumab + Enzalutamide + ADT Starting on Day 1 of each 21-day cycle, participants receive 200 mg of pembrolizumab intravenously (IV) once every 3 weeks for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally (by mouth or PO) once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met. Starting on Day 1 of each 21-day cycle, participants receive placebo IV once every 3 weeks for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.

Patients with PSMA positive scans will be randomized in a 2:1 ratio to receive either 177Lu-PSMA-617 (a targeted type of radiotherapy for prostate cancer) plus best supportive/best standard of care or to receive best supportive/best standard of care only. Best supportive/best standard of care will be determined by the treating physician but will exclude investigational agents, chemotherapy, other systemic radioisotopes, and radiotherapy. Anti-androgen drugs (such as abiraterone or enzalutamide) are allowed. The study is open-label (you will know what treatment you are getting) and patients will be monitored throughout the 6 to 10-month treatment period for survival, disease progression, and adverse events. A long-term follow-up period will include the collection of survival and treatment updates, adverse events assessment, as well as blood testing. During follow-up, patients will be contacted every 3 months by phone, email, or letter for approximately 24 months. An End of Treatment visit should occur once a patient is to enter the long term follow up. This visit should occur approximately 30 days from the last dose of 177Lu-PSMA-617 or best supportive/best standard of care, but before the initiation of subsequent anti-cancer treatment. The study has 2 arms: Arm A: 177Lu-PSMA-617 + BS/BSC (best supportive/best standard of care) Patients randomized to receive the investigational product will receive 177Lu-PSMA-617 intravenously (IV, given in clinic) every 6 weeks for a maximum of 6 cycles. + Best supportive/best standard of care (BS/BSC) Arm B: BS/BSC alone Patients randomized to this arm will receive best supportive/best standard of care (BS/BSOC) as determined by the investigator.

This trial tests the potential of adding prostatak to radiation therapy to decrease the cancer recurrence rate in patients with localized prostate cancer. In this study, radiation therapy involves external x-ray beams that are directed at the prostate in order to kill the cancer cells. Prostatak is an immunotherapy agent that functions like a vaccine, stimulating the body's immune system to recognize and destroy cancer cells. Radiation works in conjunction with prostatak to boost the scale of the immune response. The hope is that prostatak with help fight any lingering cancer that the radiation did not kill. Participants will be separated into two treatment groups and will remain naive as to which group they have been placed into. Both groups will receive the same radiation treatment as well as three injections: one 15-56 days prior to radiation, one 0-3 days before radiation, and one 15-22 days after the second injection. Additionally, oral valacyclovir will be given to patients (not part of the treatment). The difference between the groups is that one group's injections will be prostatak and the other group's injections will be an inactive agent. Note that hormone therapy can be continued if the patient so desires while on this study.

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 an imaging study to assess the safety and tolerability of a single administration of 68Ga-PSMA-R2 (a type of radioisotope that specifically targets prostate cancer), to assess the how the drug works in your body (pharmacokinetics), how the drug moves through your body (biodistribution), and appropriate dosing (dosimetry) of 68Ga-PSMA-R2. The study also aims to establish the optimal imaging method (bone scan, MRI, CT) for determining the location and burden (amount) of positive prostate cancer lesions in adult male patients with biochemical relapse (BR, rising PSA but no evidence of disease on scans) and metastatic prostate cancer (mPCa, disease visible on scans). All participants will receive 68Ga-PSMA-R2 intravenously (IV) and be followed for 28 days after infusion.

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 study involves testing different combinations of MEDI4736 (durvalumab), olaparib, and cediranib for the treatment of tumors in ovarian, triple-negative breast, lung, prostate, and colorectal cancer. Durvalumab is a type of immunotherapy agent called a PD-1 inhibitor that works by inhibiting the cancer cell's ability to escape detection by the immune system. Additionally, it stimulates the immune system to recognize and kill cancer cells. Olaparib is a targeted therapy that destroys the cancer's ability to repair its DNA, making it more susceptible to chemotherapy and radiation. Cediranib is a targeted therapy that slows cancer growth by preventing the growth of the blood vessels supplying the tumor. This trial will occur in two stages. Phase 1 will determine the maximum tolerable dosage of each drug in combination, and Phase 2 will assess the effect each combination regimen has on tumor growth.

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.

The purpose of this study is to assess the effectiveness and safety of the combination of pembrolizumab (Keytruda, a type of immunotherapy) and docetaxel (Taxotere, a type of chemotherapy) in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC but have progressed on or are intolerant to next generation hormonal agents (hormonal therapies). It is believed that the combination of pembrolizumab plus docetaxel plus prednisone (a type of steroid) is superior to placebo plus docetaxel plus prednisone with respect to overall survival. It is also believed the combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone with respect to radiographic progression-free survival (progression visible on imaging scans like a bone scan or CT scan). This study has 2 arms: Arm A: Pembrolizumab + Docetaxel On Day 1 of each 21-day cycle, participants receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours and 1 hour prior to docetaxel administration PLUS docetaxel (dose is based on participant’s weight) by intravenous (IV) infusion for up to a maximum of 10 cycles (approximately 7 months). Participants receive prednisone 5 mg by oral tablets twice daily during each docetaxel cycle up to a maximum of 10 cycles (approximately 7 months). Participants also receive pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for up to a maximum of 35 cycles (approximately 2 years). Arm B: Placebo + Docetaxel On Day 1 of each 21-day cycle, participants receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours and 1 hour prior to docetaxel administration PLUS docetaxel (dose is based on participant’s weight) by IV infusion for up to a maximum of 10 cycles (approximately 7 months). Participants receive prednisone 5 mg by oral tablets twice daily during each docetaxel cycle up to a maximum of 10 cycles (approximately 7 months). Participants also receive placebo by IV infusion on day 1 of each 21-day cycle for up to a maximum of 35 cycles (approximately 2 years).

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 trial is designed based on the potential for high doses of ascorbic acid (vitamin C) to slow cancer progression by killing cancer cells. Prostate cancer cells have a tendency to absorb ascorbic acid, and in high doses ascorbic acid produces hydrogen peroxide that is toxic to the cancer cells. The study specifically investigates whether a combination of docetaxel and ascorbic acid causes a greater reduction in prostate-specific antigen than docetaxel alone. Docetaxel is a chemotherapy drug that kills cancer cells by stopping cellular division. Persons eligible for this study must have advanced metastatic castration-resistant prostate cancer but not have been previously treated with chemotherapy. Participants in this study will be randomly separated into two treatment groups. The study consists of eight 21-day cycles. Group one and two patients will receive standard treatment of docetaxel injections on the first day of every cycle. Group one will receive the experimental treatment of ascorbic acid injected three times per week, while group two will receive an inactive saline solution injected three times per week.  Participants will not know which injections they are receiving.

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 research is being done to determine whether mesenchymal stem cells (MSCs, a particular type of stem cells found in the bone marrow) will migrate to the sites of prostate cancer following an intravenous (IV) infusion of the MSCs in men prior to receiving a prostatectomy as treatment for newly diagnosed prostate cancer. MSCs leave the bone marrow and travel to places in the body where there is inflammation or tissue damage. This study will help us to determine how many of these MSCs migrate to sites of prostate cancer after they are given to intravenously. A second goal of this study is to test whether MSCs given prior to removal of the prostate can preserve erectile function in men undergoing a prostatectomy.

The MSCs being used in this study are obtained from healthy volunteers. These healthy volunteers are carefully screened and tested with the same methods used to screen donors for bone marrow transplant to treat leukemia. The MSCs in this bone marrow will be removed and purified under sterile conditions prior to use in this study.

Specific treatment:

Patients will receive 4 bags of mesenchymal stem cells through an IV given once 4 to 8 days prior to having your prostate removed.

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 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.

Some prostate cancer keeps growing even when testosterone in the body drops to very low levels. This is called castrate-resistant prostate cancer. One treatment is enzalutamide (a type of anti-androgen or hormonal therapy), but it only works for a certain amount of time and then the cancer becomes resistant to it. Researchers want to see if adding the treatment CRLX101 (a type of anti-HIF-1Alpha inhibitor or targeted therapy) could make enzalutamide work again for people who have already had it. This study has 1 arm: CRLX101 + enzalutamide CRLX101 will be administered by intravenous (IV) infusion (given in clinic) once every 2 weeks. Dosing to be determined at time of enrollment. Enzalutamide 160 mg will be administered orally once daily beginning on Day 2 of treatment.

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 single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, and immunogenicity (the ability of the drug to provoke an immune response) of neoadjuvant Dupixent (Dupilumab, a type of immunotherapy) given prior to radical prostatectomy in men with high-risk localized prostate cancer. Patients will be recruited from the outpatient urology clinic. All men will be treated with dupilumab 600 mg subcutaneously (SQ) on day 1, and then 300 mg SQ on days 8, 15, 22, 29, 36, 43. They will then undergo surgery on day 57 (14 days after the last dose of Dupixent). Prostate glands will be removed at the time of radical prostatectomy, and prostate tissue will be examined. Follow-up evaluation for adverse events will occur 30 days and 60 days after surgery. Patients will then be followed by their urologists according to standard institutional practices, but will require PSA evaluations every 3 months during year 1 and every 6 months during years 2-3.

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.

Prostate cancer is the second leading cause of cancer deaths in American men. Few options exist to create images of this type of cancer. Researchers think an experimental radiotracer (or type of contrast) called 18F-DCFPyL could find sites of cancer in the body.

The objective of this study is to see if 18F-DCFPyL can identify sites of prostate cancer in people with the disease.

Participants will be assigned to 1 of 2 groups based on their PSA.

Participants will have 18F-DCFPyL injected into a vein. About 2 hours later they will have a whole-body Positron Emission Tomography/Computed Tomography (PET/CT). For the scan, they will lie on their back on the scanner table while it takes pictures of the body. This lasts about 50 minutes. On another day, participants will have 18F -NaF injected into a vein. About 1 hour later, they will have a whole-body PET/CT.

Participants will be contacted 1-3 days later for follow-up. They may undergo PET/Magnetic Resonance Imaging (MRI) either after having an 18F-DCFPyL PET/CT, or in place of PET/CT imaging. A tube may be placed in the rectum. More coils may be wrapped around the outside of the pelvis.

If the 18F-DCFPyL PET/CT is positive participants will be encouraged to undergo a biopsy of one of the tumors. The biopsy will be taken through a needle put through the skin into the tumor.

Participants will be followed for 1 year. During this time researchers will collect information about their prostate cancer, such as PSA levels and biopsy results.

About 4-6 months after scanning is completed, participants may have a tumor biopsy. The biopsy will be taken through a needle put through the skin into the tumor.

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).

The purpose of this first-in-human study of CX-2009 (a type of targeted therapy) is to characterize the safety, tolerability, activity in the body, and antitumor activity of CX-2009 in adult subjects with metastatic or locally advanced unresectable solid tumors. This study has 1 arm: CX-2009 Escalation and Expansion Monotherapy CX-2009 given intravenously (IV) in clinic – dosing and frequency to be provided by treatment team.

The purpose of this study is to assess the safety and effectiveness of nivolumab (a type of immunotherapy) in combination with rucaparib (a type of targeted therapy), docetaxel (a type of chemotherapy), or enzalutamide (a type of hormonal therapy) in participants with castration-resistant prostate cancer that has spread. This study has 3 arms: Arm A: nivolumab + rucaparib Specified dose on specified days to be provided by treatment team. Nivolumab is given intravenously (IV), rucaparib is given orally (po or by mouth). Arm B: nivolumab + docetaxel + prednisone Specified dose on specified days to be provided by treatment team. Nivolumab is given IV, docetaxel is given IV, prednisone is given orally. Arm C: nivolumab + enzalutamide Specified dose on specified days to be provided by treatment team. Nivolumab is given IV, enzalutamide is given orally.

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.

Prostate cancer is a common disease in men treated using surgery, radiation therapy and/or hormonal therapy. Clinical prognosis relates to stage and grade of disease. Recent advances in omic analysis (using multiple sources of specific information about prostate cancer cells/tumor cells) may offer additional information to the physician about prognosis and radiation response. We propose to establish a protocol to incorporate omic analysis into the evaluation and treatment of patients with prostate cancer. The study has 2 arms: Arm A: Radiation Therapy Prostate stereotactic body radiation therapy (SBRT) and intensive modulated radiation therapy (IMRT) or the combination of both (boost). Arm B: Healthy control Age-matched male who has no known prostate cancer.

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).

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, when 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 (or type of contrast) 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.

Participants in Group 1 may have surgery to remove their prostate gland or a biopsy to remove some prostate tissue. This procedure will be standard of care and is not a part of this study. They will also have an extra MRI scan of their prostate. For this, a tube, called an endorectal coil, will be placed in their rectum. Other tubes may be wrapped around the inside of their pelvis. A contrast agent will be given by IV.

Participants in Group 2 may also undergo an MRI of the pelvis and may have a biopsy of abnormalities found on the 18F-DCFyL scan.

Participants will have data about their prostate cancer collected for up to 1 year.

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.

The primary purpose of this study is to evaluate the tolerability and safety profile of ASP8374 (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 tumor malignancies. The secondary purpose of this study is to evaluate the anti-tumor effect, duration of response, persistence of response after discontinuation, and disease control rate of ASP8374 when administered as a single agent and in combination with pembrolizumab. This study has 2 arms: Arm A: ASP8374 Participants will be enrolled in the escalation cohorts or expansion cohorts and receive ASP8374 (monotherapy) intravenously on Day 1 of every 3-week cycle (up to a maximum of 8 dose strengths). Arm B: ASP8374 and pembrolizumab Participants will be enrolled in the escalation cohorts or expansion cohorts and receive ASP8374 and pembrolizumab (combination therapy) intravenously on Day 1 of every 3-week cycle (up to a maximum of 5 dose strengths of ASP8374 and one fixed dose strength of pembrolizumab).

CRLX101 consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or nanoparticle drug travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib (a type of targeted therapy, a PARP inhibitor) is a drug that may stop cancer cells from repairing the DNA damage caused by chemotherapy. Researchers want to see how safe it is to give CRLX101 and olaparib together and to see how well the combination treats specific types of cancer. Patients will receive the two study drugs in 28 day cycles (1 cycle = 28 days). CRLX 101 will be given intravenously (IV) on days 1 and 15 and the olaparib will be taken by mouth days 3-13 and 17-26.

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.

The purpose of this study is to assess the safety and tolerability of VERU-111 (a type of targeted therapy) and to determine the maximum tolerated dose of VERU-111 in patients with metastatic, castration resistant prostate cancer who have failed a novel androgen blocking agent therapy (hormonal therapy). Treatment: VERU-111 will be given at various dose levels daily on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until there is a dose-limiting toxicity or disease progression is observed.

177Lu-PSMA-R2 is radioconjugate with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous (IV) administration of 177Lu-PSMA-R2, the PSMA-R2 targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on the majority of prostate tumor cells. This study is intended to investigate the safety, tolerability, and radiation dosimetry (dosing) of 177Lu-PSMA-R2, and further assess preliminary efficacy (effectiveness) data in patients with metastatic castration-resistant prostate cancer (mCRPC). Treatment: 177Lu-PSMA-R2 radio-ligand therapy will be given at various dose levels.

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

This is a two-arm, open label phase 1b/2 with an oral administration of CPI-1205 (a type of targeted therapy) in combination with either enzalutamide or abiraterone/prednisone (types of hormonal therapy) in male patients with metastatic castration-resistance prostate cancer (mCRPC). This study has 2 arms: with both arms, CPI-1205 will be dose escalated based on tolerance (side effects). Arm A: Enzalutamide given per standard of care + CPI-1205 Arm B: Abiraterone + prednisone given per standard of care + CPI-1205

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.

Single arm, multicenter, open-label Phase II study of the effects of testosterone in combination with nivolumab (Opdivo) in men with metastatic castration-resistant prostate cancer who previously progressed on at least one novel androgen-receptor targeted therapy (like Abiraterone acetate or Enzalutamide). Up to one taxane agent (chemotherapy like Taxotere or Cabazitaxel) is permitted. The study has 1 arm: Bipolar Androgen Therapy + Nivolumab: Patients will be treated with testosterone cypionate 400mg given as an intramuscular (IM) injection every 4 weeks for a lead-in period of 12 weeks. After the lead-in period, all patients will be treated with nivolumab 480mg given intravenously (IV) every 4 weeks and maintained on testosterone cypionate 400mg IM every 4 weeks.

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 ATR inhibitor BAY1895344 (a type of targeted therapy) is developed for the treatment of patients with advanced solid tumors. The purpose of this trial is to evaluate the safety and tolerability of BAY1895344, and to identify the maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further, the response of the cancer to the treatment will be determined. All subjects receive study drug: BAY1895344 will be given orally (po or by mouth) at different doses and on different scheduled to be provided by the treatment team.

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 primary purpose of this study is to evaluate the tolerability and safety profile of PF-06821497 (a type of targeted therapy) when administered as a single agent in participants relapsed/refractory small cell lung cancer (SCLC), castration resistant prostate cancer (CRPC) and follicular lymphoma (FL); characterize how PF-06821497 works in the body when administered as a single agent; and determine the recommended dose of PF-06821497 when administered as a single agent. This study will also evaluate the anti-tumor effect of PF-06821497 when administered as a single agent. All participants receive study drug. PF-06821497 is taken orally (po or by mouth) daily. Dose will be provided by treatment team.