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.

The purpose of this study is to determine the benefit and safety of relugolix (a type of hormonal therapy) given orally at 120 mg once daily for 48 weeks, on maintaining serum testosterone suppression to castrate levels in patients with androgen-sensitive advanced prostate cancer.

Patients will be randomized to one of two arms:

Arm A: Relugolix

Relugolix will be taken orally (at home) 120 mg tablet once daily.

Arm B: Leuprolide Acetate (standard of care)

Leuprolide acetate depot suspension, 22.5 mg will be given (in clinic) one every 3 months by subcutaneous or intramuscular injection.

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 study will assess effectiveness and safety of niraparib (Zejula, a type of targeted therapy, a PARP inhibitor) in combination with abiraterone acetate (Zytiga, a type of hormonal therapy) and prednisone (a type of steroid) for the treatment of participants with metastatic prostate cancer. In participants with metastatic prostate cancer, DNA-repair gene defects are identified in approximately 15 % to 20% of tumors. The study will consist of 4 phases: a prescreening phase for biomarker evaluation only, a screening phase, a double-blind treatment phase, and a follow up phase. During the prescreening phase participants will be evaluated for DNA-repair gene defects and then will be assigned to one of the 2 cohorts based on their biomarker status. Treatment will be administered daily and is planned to be continuous until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. The study has 2 arms: Arm A: Niraparib + Abiraterone Acetate-Prednisone (AA-P) Participants will receive oral administration of niraparib 200 milligram (mg) (2 capsules of 100 mg each) in combination with abiraterone acetate (AA) 1000 mg (4 tablets of 250 mg each) tablets and prednisone 10 mg (2 tablets of 5 mg each) tablets daily in each cycle (each cycle of 28 days). Arm B: Placebo + AA-P Participants will receive oral administration of matching placebo capsules in combination with AA 1000 mg (4 tablets of 250 mg each) tablets and prednisone 10 mg (2 tablets of 5 mg each) tablets daily in each cycle (each cycle of 28 days).

The purpose of this trial is to assess whether adding enzalutamide after salvage radiation therapy (SRT) prolongs the amount of time during which the prostate-specific antigen (PSA) does not rise, as opposed to SRT alone. SRT is radiation delivered to the area around where the prostate used to be in patients who have just undergone a prostatectomy in order to kill any residual cancer cells. Enzalutamide is a hormone therapy agent that is normally given to patients with advanced metastatic prostate cancer to prevent their cancer from using testosterone to continue to grow and spread. However, previous studies have shown that there is a potential benefit to treating with enzalutamide earlier. Persons eligible for this study are those whose PSA is rising after having undergone a radical prostatectomy. Participants will be randomly separated into two treatment groups. Both groups will receive an oral pill to take daily for six months. However, one group's pills will contain an inactive agent and the other group will receive the enzalutamide pills. Neither group will know which pill they have received. Both groups will receive the same treatment SRT regimen starting two months after they begin taking the pills.   

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.

The primary goal is to prospectively estimate the median progression free survival (PFF, period of time with no disease growth) of African American and Caucasian men with mCRPC (metastatic castrate resistant prostate cancer) taking apalutamide (a type of anti-androgen or hormonal therapy), abiraterone acetate (a type of anti-androgen or hormonal therapy), and prednisone (a type of steroid given with anti-androgen therapy). Fifty patients will be enrolled in each group (African American and Caucasians). The study has two arms (African American and Caucasian patients), but each receives the same treatment: Apalutamide 240mg orally (by mouth) once daily + abiraterone acetate 1000mg orally once daily, and prednisone 5 mg twice daily. Each cycle = 4 weeks throughout the treatment period.

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 multicenter study will evaluate safety and efficacy of niraparib (a type of targeted therapy, a PARP inhibitor) in combination with other anti-cancer agents. Two combinations are being studied: the first combination study will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody, JNJ-63723283 (a type of immunotherapy) in participants with metastatic castration-resistant prostate cancer (mCRPC). The second combination will combine niraparib with abiraterone acetate plus prednisone (AA-P, a type of hormonal therapy) in mCRPC participants with DNA-repair gene defects (DRD). The purpose of this study is to establish the recommended phase 2 dose (RP2D) of niraparib combination therapies of Part 1 and to evaluate the antitumor activity and safety of niraparib combination therapies of Part 2. Treatment: Combination 1: Niraparib and JNJ-63723283 Dose regimen 1: The participants will receive niraparib 200 milligram (mg) orally (po) once daily in combination with JNJ-63723283 240 mg intravenously (IV) once every 2 weeks in 28-day treatment cycles. Dose regimen 2: The participants will receive niraparib 200 mg orally once daily in combination with JNJ-63723283 480 mg IV once every 4 weeks in 28-day treatment cycles. Combination 2: Dose Expansion: Niraparib + AA-P (abiraterone plus prednisone) Participants will receive niraparib 200 mg orally once daily in combination with abiraterone acetate 1000 mg (4 tables of 250 mg) orally once daily plus 10 mg prednisone (5 mg orally twice daily) throughout treatment phase.

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.

This study will analyze tumor genetics in relation to treatment methods. Tumor cell DNA and RNA are collected from each participant pre- and post-treatment with either abiraterone, enzalutamide, or chemotherapy, and patients' response to their treatment will be observed. Using both the information on patient outcome and tumor cell characteristics, the goal is to identify biomarkers in the tumor cells that predict the success or failure of certain treatments. This information will better inform future treatment decisions and guide therapy choices. Knowing how the tumor genetics are altered after a specific treatment also has the potential to inform secondary treatment options.  

Just like every person is genetically unique, so is the genetic makeup of each person's tumor cells. The purpose of this trial is to use genetic analysis of tumors to identify abnormalities and, based on these abnormalities, determine a course of treatment. Participants eligible for this trial must have a solid tumor that is progressing despite treatment. Participants will undergo a biopsy to collect a sample for genetic tumor analysis. Afterwards, they will be assigned one of 24 different treatment protocols based on the analysis results. At the end of treatment, a second biopsy will be performed to determine the patient's response to treatment.

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.

This study is an open-label, non-randomized, dose escalation study in subjects with metastatic castrate resistant prostate cancer (mCRPC) who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel), or cannot tolerate either or both therapies.

There will be two treatment phases:

Phase 1 (dose escalation stage): Multiple dose escalations of GT0918 (proxalutamide, a type of anti-androgen or new type of hormonal therapy) to establish safety and tolerability.

Phase 2 (dose expansion stage): Identify two dose levels from Phase 1 to further evaluate the safety, tolerability and antitumor activity of GT0918 (proxalutamide).

GT0918 (proxalutamide) is taken orally (at home) once daily on an empty stomach, at various dose levels.

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.

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.

This is a randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer (meaning a rising PSA) and PSA doubling time ≤ 9 months at the time of study entry. Patients will be randomized to one of three treatment arms: (1) Control arm consisting of degarelix (Firmagon) monotherapy, a type of androgen deprivation or hormonal therapy (2) Experimental arm consisting of apalutamide (a type of anti-androgen, or hormonal therapy) in combination with degarelix, and (3) Experimental arm consisting of apalutamide, abiraterone acetate (Zytiga, a type of anti-androgen, or hormonal therapy) + prednisone (a type of steroid), and degarelix. Patients will be treated for a maximum duration of 52 weeks. They will then enter a follow up phase lasting until the time of PSA progression (when the PSA starts to rise again), development of metastasis, or patient withdrawal from study, whichever occurs first. The primary endpoint of the study is PSA progression-free survival (meaning no rise in PSA and no evidence of metastatic disease). The study is comparing the effectiveness of each arm compared to the other arms of the study. Treatment: Arm 1: Degarelix Monotherapy Patients will receive Degarelix by subcutaneous injection (s.c. or s.q., an injection into the fat just below the skin) every 28 days. Patients will receive a loading dose of 240 mg (two 120 mg injections) on cycle 1 day 1, followed by maintenance dose of 80 mg subcutaneous injection on day 1 of subsequent cycles. Arm 2: Degarelix/Apalutamide Degarelix will be given the same as in Arm 1. Patients will also take apalutamide 240 mg (four 60 mg tablets) orally (by mouth) once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period. Arm 3: Degarelix/Apalutamide/Abiraterone/Prednisone Degarelix will be given the same as in Arm 1 and Arm 2. Apalutamide will be given the same as in Arm 2. Patients will also take abiraterone acetate 1000 mg (four 250 mg tablets) and prednisone 5mg orally once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period.

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.

The purpose of this study is to determine whether anti-testosterone medications, when administered before, during, and after high-dose, precision radiation, will be effective in preventing the prostate cancer from returning.

Eligible patients will receive a total of 6 months of leuprolide (Lupron, a type of hormonal therapy), abiraterone (Zytiga, a type of hormonal or anti-androgen therapy), and ARN-509 (Apalutimide, a type of hormonal or anti-androgen therapy) to begin three months prior to radiation therapy and continuing until approximately 3 months post-radiation therapy. Patients will be assessed every 4 weeks (one cycle = 28 days) throughout their treatment with the study drugs, and at least once during radiation therapy.

Olaparib (a type of targeted therapy called a PARP inhibitor) has demonstrated preliminary effectiveness in fighting metastatic castration-resistant prostate cancer (mCRPC). While PARP inhibition is showing promise in initial studies, reserving its use for mCRPC patients may not be the optimal timing for olaparib therapy. PARP inhibition has not been tested in earlier disease states for prostate cancer. The hypothesis is that olaparib may show anti-tumor effects (targeting cancer cells not yet visible on CT or bone scans) in high-risk patients following radical prostatectomy.

Patients will take olaparib 300 mg orally (at home) twice daily, approximately 12 hours apart. Each cycle will be 28 days.

The study aims to evaluate the combination of GSK525762 with other agents that have been shown to be effective in the treatment of CRPC or metastatic CRPC (mCRPC), including approved agents (anti-androgen or hormonal therapies like abiraterone, enzalutamide) as well as investigational agents for mCRPC that have proven to show efficacy (that they work) and can be combined with GSK525762.

As a first step, the combination of GSK525762 will be evaluated as a combination with abiraterone (Zytiga) or enzalutamide (Xtandi) in men with metastatic or advanced castrate-resistant prostate cancer who have progressed on at least one line of prior androgen receptor (AR, hormonal therapy)-targeted therapy. This study is designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) based on safety, tolerability, pharmacokinetic (how a drug works in the body), and efficacy (how well the drug works) profiles of GSK525762 in combination with either abiraterone (Arm A) or enzalutamide (Arm B).

Arm A: GSK525762 + abiraterone

Two dose combinations, 60 mg or 80 mg of oral GSK525762 will be administered once daily (at home). There is also a possibility of dose reduction to 40 mg in case of toxicity. Subjects may also receive prednisone (5 mg taken orally twice daily at home) in combination with abiraterone (1000 mg taken orally once daily at home) dosing.

Arm B: GSK525762 + Enzalutamide

Two to three dose combinations 80 mg, 100 mg and 120 mg of oral GSK525762 will be administered once daily (at home). There is also a possibility of dose reduction to 60 mg in case of toxicity. Enzalutamide 160 mg is taken orally once daily (at home).

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.

The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib (a type of targeted therapy, a PARP inhibitor) in men with metastatic castration resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies (discovered through testing of tumor tissue). The study has 1 arm: Niraparib Participants will receive Niraparib by mouth (at home) 300 mg once daily.

This is an open-label, multi-center, single-dose study of AuroLase Therapy in the focal ablation (removal or destruction) of prostate cancer tissue using nanoparticle directed irradiation (a new type of radiation therapy). Patients will be men > 45 years of age with low to intermediate risk localized (meaning within the prostate) prostate cancer with cancer visible on MRI and confirmed focal areas of prostate cancer using MR US Fusion Guided Biopsy (a type of biopsy that uses imaging to guide where the biopsy is taken from). Patients will have no disease detected by ultrasound guided biopsy outside of areas visualized on MR imaging (meaning no cancer visible outside the prostate, or no metastatic disease). The goal of this study is to determine the effectiveness of using MRI/US fusion imaging technology to direct focal ablation of prostate tissue using nanoparticle-directed laser irradiation. Effectiveness will be assessed by MRI /Ultrasound guided biopsy at 3 months and again at 1 year after laser treatment. The study has 1 arm: AuroShell particle infusion A single intravenous (IV) infusion of AuroShell particles 12 to 36 hours prior to ultrasound-guided laser irradiation using an FDA cleared laser and an interstitial optical fiber.

The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared to another marketed drug for advanced prostate cancer (LUPRON DEPOT) in patients with prostate cancer and cardiovascular disease. There are 2 arms in this study: Arm 1: Degarelix (FIRMAGON) given per standard of care. Arm 2: Leuprolide (LUPRON DEPOT) given per standard of care.

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.

Obesity and metabolic syndrome are prevalent among prostate cancer patients. Having an elevated insulin level in the blood is associated with a shorter median time to cancer progression and median overall survival in patients with an elevated PSA after prior treatment. Androgen deprivation therapy (ADT) with drugs like bicalutamide (a type of hormone therapy) is frequently used in this patient population, with no proven benefit, which may increase mortality and morbidity (death or serious negative effects).This study evaluates how metformin (an oral drug that lowers blood sugar) in combination with bicalutamide affects prostate cancer. 1 cycle = 28 days The study has 2 arms: Arm A: Bicalutamide Bicalutamide 50 mg taken orally once daily beginning at cycle 3 to cycle 8. Patients will be observed, without treatment during Cycle 1 and 2. Arm B: Metformin and Bicalutamide Metformin 1000mg taken orally twice a day + Bicalutamide 50 mg taken orally once daily beginning at cycle 3. During Cycle 1 and 2, Metformin will be gradually increased, in order to minimize gastrointestinal discomfort. Metformin treatment will be started at 500 mg taken orally twice a day, and increased by an increment of 500 mg daily every week as long, as the drug is tolerated, up to a maximum of 1000 mg taken orally twice a day.

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.

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 study is to assess the safety of treating men with oligometastatic prostate cancer (meaning the cancer has spread outside the prostate gland to other organs) with the following multi-treatment therapy: first, systemic chemo-hormonal therapy with up to six months of neoadjuvant (meaning before surgery or radiation) androgen deprivation (hormonal therapy) and up to six cycles of chemotherapy; second, definitive local tumor control with a prostatectomy with or without adjuvant (meaning after surgery) radiation therapy; and third, consolidative stereotactic radiation to oligometastatic lesions (tumors outside of the prostate). Patients will receive one year of androgen deprivation (hormonal therapy). Androgen blockade (another type of hormonal or anti-androgen therapy) will remain the same throughout the study.

This study is intended to be curative and/or to delay the need to start hormonal therapy for recurrent prostate cancer after definitive therapy.

Specifically, patients will receive the following therapies:

1. Leuprolide Acetate (hormonal therapy) 22.5mg by intramuscular (IM) injection once every three months.

2. Bicalutamide (Casodex, another type of hormonal or anti-androgen therapy) 50mg taken orally (at home) once daily.

3. Docetaxel (Taxotere, chemotherapy) 75 mg/m2 given intravenously (IV in the clinic) once every 3 weeks, up to 6 cycles.

4. Prostatectomy (surgery) – the removal of the entire prostate gland, plus some surrounding tissue.

5. Radiation – Five high-dose radiation treatments to the metastatic (tumor that has spread to other parts of the body) sites.

The purpose of this study is to determine how patients with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency (an abnormality in the DNA or genetic information that can be tested for), respond to treatment with rucaparib (Rubraca, a type of targeted therapy). Testing can be done on blood (taken through a blood draw) or tumor tissue (taken from tissue previously collected during surgery or a biopsy, or taken from a fresh biopsy).

It is hypothesized that rucaparib will have anti-tumor effects (cause tumors to shrink) in patients with specific DNA or genetic abnormalities.

Rucaparib is a drug taken orally (at home) once daily.

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.

Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. Radiation therapy uses high-energy x-rays to kill tumor cells. This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer. This study has 2 arms: Arm A: Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT) or 3D-conformal radiation therapy (3D-CRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy. Arm B: Patients undergo whole-pelvic radiotherapy (WPRT) (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.

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.

The purpose of this study is to assess the safety of treating men with oligometastatic prostate cancer (meaning the cancer has spread outside the prostate gland to other organs) with the following multi-treatment therapy: first, systemic chemo-hormonal therapy with up to six months of neoadjuvant (meaning before surgery or radiation) androgen deprivation (hormonal therapy) and up to six cycles of chemotherapy; second, definitive local tumor control with a prostatectomy with or without adjuvant (meaning after surgery) radiation therapy; and third, consolidative stereotactic radiation to oligometastatic lesions (tumors outside of the prostate). Patients will receive a total of two years of androgen deprivation (hormonal therapy). Androgen blockade (another type of hormonal or anti-androgen therapy) will remain the same throughout the study.

This study is intended to be curative and/or to delay the need to start hormonal therapy for recurrent prostate cancer after definitive therapy.

Specifically, patients will receive the following therapies:

1. Leuprolide Acetate (hormonal therapy) 22.5mg by intramuscular (IM) injection once every three months.

2. Bicalutamide (Casodex, another type of hormonal or anti-androgen therapy) 50mg taken orally (at home) once daily.

3. Docetaxel (Taxotere, chemotherapy) 75 mg/m2 given intravenously (IV in the clinic) once every 3 weeks, up to 6 cycles.

4. Prostatectomy (surgery) – the removal of the entire prostate gland, plus some surrounding tissue.

5. Radiation – Five high-dose radiation treatments to the metastatic (tumor that has spread to other parts of the body) sites.

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).

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.

Metastatic castration resistant prostate cancer (mCRPC) keeps growing even when the amount of testosterone in the body is reduced to very low levels. mCRPC is incurable. Researchers want to develop vaccines to teach the immune system to target and kill cancer cells. They want to test three of these vaccines (ETBX-071, ETBX-061, and ETBX-051) against mCRPC. Participants will get the vaccines as shots under the skin every 3 weeks for 3 doses. They may then have the shots every 8 weeks for up to 1 year. This study has 1 arm: doses of vaccine will initially be escalated to monitor tolerance of the vaccine combination. ETBX-071; adenoviral PSA vaccine given by subcutaneous injection every 3 weeks for 3 immunizations. ETBX-061; adenoviral MUC1 vaccine given by subcutaneous injection every 3 weeks for 3 immunizations. ETBX-051; adenoviral brachyury vaccine given by subcutaneous injection every 3 weeks for 3 immunizations.

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.

The study is a randomized, open-label study designed to assess the efficacy of sipuleucel-T (Provenge, a type of immunotherapy) in reducing the progression of lower risk non-metastatic prostate cancer compared to subjects followed on active surveillance (no active treatment) as standard of care. The study has 2 arms: Treatment Group: Sipuleucel-T Sipuleucel-T is an autologous cellular immunotherapy available as a suspension for intravenous infusion. Subjects randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T approximately 2 weeks apart. Control Arm: Active Surveillance Subjects randomized to the control arm will be followed on active surveillance, with monitoring done per standard of care.

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.