Prostate Cancer Trials

Docetaxel is an already-approved chemotherapy drug used to treat prostate cancer because of its ability to kill rapidly dividing cells. DCVAC/PCa is an experimental active cellular immunotherapy drug that activates the body's immune response to the cancer by utilizing the type of cells best able to trigger a large-scale immune response. This trial seeks to determine whether a combination of chemotherapy and DCVAC/PCa is more effective than chemotherapy alone in preventing the cancer from spreading for a longer period of time. Patients eligible for this study are those with metastatic castration-resistant prostate cancer. Participants will be randomly separated into two groups. One group will receive the standard dose of docetaxel and the other group will receive the standard dose of docetaxel plus the DCVAC/PCa (experimental drug). Participants will not know which group they are in (double-blind trial).

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.

Nivolumab and Ipilimumab are drugs from a class of immunotherapy agents called monoclonal antibodies that have recently been approved as treatment for several cancers besides prostate cancer. While they each have different target proteins, both drugs prevent the expression of a specific protein either on or produced by tumor cells that stops the immune system from attacking the cancer. These drugs free the T-cells (a type of immune cell) so that they can trigger an immune response that kills tumor cells and halt the growth of the cancer. The hope is that this combination of treatments will significantly lower prostate-specific antigen. Patients eligible for this trial are those with metastatic castration-resistant, hormone-resistant prostate cancer who are AR-V7 positive, making them highly unlikely to respond to hormone therapy. Participants will receive injections of both nivolumab and ipilimumab every three weeks for a total of 12 weeks and will then continue with injections of nivolumab every two weeks for a total of 36 weeks.   

Enzalutamide is a hormone therapy agent that works by preventing the prostate cancer cells from using testosterone to fuel cancer growth. GSK2636771 or PI3K-beta inhibitor is an experimental drug that is being tested for its potential to specifically target tumor cells and prevent them from continuing to grow. The hope is that because GSK2636771 targets only tumor cells, it can be given in higher doses and therefore have a greater impact than some of the current more-toxic therapies. Participants in this study must be patients with metastatic castration-resistant prostate cancer who are progressing despite taking enzalutamide. This trial is designed in two parts. Part 1 will determine the maximum tolerable dose of the GSK2636771 and part 2 will use the determined dosage and study the long-term effects of maintaining this dose. Each part will include two separate groups of patients and all of the patients will be aware of which part of the trial they are participating in. All patients will continue to take enzalutamide as part of the trial.

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 to test the difference in prolonging life between treatment with a luteinizing hormone releasing hormone (LHRH) agonist plus bicalutamide versus an LHRH agonist plus the experimental drug TAK-700. An LHRH agonist is a type of hormone therapy that tells a part of the brain to stop producing the hormone that signals the testicles to produce testosterone. Bicalutamide affects the cancer by preventing tumor cells from using testosterone to stimulate cancer growth. TAK-700 is designed to stop testosterone production by blocking an enzyme found in the brain and the testes required for testosterone production. Participants will be randomly separated into two treatment groups, and following randomization they will be made aware of which treatment they are to receive. Both groups will receive a regimen of an LHRH agonist. Additionally, one group will receive bicalutamide to take orally once daily and the other group will receive TAK-700 to take orally twice daily.

The purpose of this study is to test the effectiveness of the experimental drug 177Lu-J591 (a type of radiation therapy that specifically targets cancer cells) in combination with ketoconazole (an FDA-approved anti-fungal drug) and hydrocortisone (an FDA-approved steroid) against prostate cancer.

This research is being conducted because the standard treatments for prostate cancer that has returned after surgery and/or radiation and progressed has on initial hormonal therapy are not curative. Existing treatments, such as the ketoconazole used as part of this study may decrease prostate-specific antigen temporarily, but unfortunately the cancer continues to grow. This experimental drug is designed to seek out all of the prostate cancer cells and deliver a lethal dose of radiation the cancer, but not to normal cells.

The experimental drug in this study includes an antibody called J591. It is a protein molecule that can bind to a specific site on a prostate cancer cell. A very energetic radioactive metal called 177Lutetium (abbreviated 177Lu) is attached to the J591 antibody. The fully assembled drug is called "177Lu-J591." The study will assess the potential of the energy given off by the radioactive compound to kill cancer cells. This study may also involve the use of 111Indium (abbreviated 111In). This is energetic radioactive particle that does not generally give off enough energy to kill cancer cells, but allows researchers to take pictures. This radioactive particle is also attached to the J591 antibody (called 111In-J591) and will serve as a placebo (treatment with no active medicine).

Dosing will be either:

1. Ketoconazole 400 mg taken orally (at home) three times a day PLUS hydrocortisone 20 mg each morning and 10 mg each evening taken orally (at home) for four weeks. This is followed by a 177Lu-J591 infusion (given intravenously in the clinic) while continuing to take the ketoconazole and hydrocortisone, OR

2. Ketoconazole 400 mg taken orally (at home) three times a day PLUS hydrocortisone 20 mg each morning and 10 mg each evening taken orally (at home) for four weeks. This is followed by a 111In-J591 (placebo) infusion (given intravenously in the clinic) while continuing to take the ketoconazole and hydrocortisone.

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 trial compares the effectiveness of the hormone therapy agents bicalutamide and apalutamide in combination with radiation therapy in preventing recurrence of metastases. Both bicalutamide and apalutamide are hormone therapy agents that work similarly by preventing testosterone from stimulating cancer cell growth. However, bicalutamide is an already-approved treatment, while apalutamide is experimental. Previous studies have shown that apalutamide can successfully prevent the cancer from spreading for a longer period of time than other similar hormone therapy drugs and do so with less severe side effects. Participants will be randomly separated into two treatment groups, an experimental group and a control group, and will remain unaware as to which group they are in. Each group will be given two pills to take daily. One of these pills will be an inactive agent and one will be an active study drug. The active study drug for the control group is bicalutamide, while the active study drug for the experimental group is apalutamide. All participants will begin radiation therapy eight weeks into this treatment.

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.   

This is a long-term prospective registry to evaluate the impact of Prolaris testing on therapeutic decisions in patients with newly diagnosed favorable intermediate-risk localized prostate cancer and to summarize clinical oncologic outcomes. The design of the study is non-interventional, and therefore the protocol will not require a specific treatment plan for study participants. However, in the absence of a universally accepted timeframe for repeat biopsies within existing active surveillance recommendations, study sites will be encouraged to monitor patients for disease progression as per the standard of care with the expectation of a repeat biopsy within 18 months of the initial biopsy. Patients who undergo Prolaris testing will be included in the registry as well as patients who do not undergo Prolaris testing. Data collection may extends over a 3-8 year period. During this time, data is collected on the treatment initiated, any follow-up prostate biopsy performed in patients initially treated with active surveillance, definitive treatments performed (with pathology data if surgical therapy is performed), and the reasons definitive treatment was pursued, as well as data related to disease progression such as biochemical (PSA) recurrence, development of prostate cancer metastases, or disease specific death. There is no treatment during this study. The study has 2 arms: Arm A: Patients who receive Polaris testing Arm B: Patient who do NOT receive Polaris testing

This is a phase 1 trial aimed at testing mesenchymal stem cells as a potential new method for future drug delivery. The stem cells would be injected into a precise area with the hope of maximizing drug delivery and disease response while minimizing toxic effects. For this trial, donor stem cells are injected into the site of the prostate cancer before the patient undergoes a prostatectomy. The first three patients will receive between 1x10^6 cells/kg and 1x10^8 cells/kg four days before surgery, and the remaining patients will receive between 2x10^6 cells/kg and 2x10^8 cells/kg four to six days before surgery.    

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 trial analyzes the specific response of prostate cancer when the androgen-deprivation therapy drug goserelin and enzalutamide are used before a prostatectomy. Goserelin is used in patients with localized prostate cancer to decrease the amount of testosterone the body produces. Enzalutamide is used to treat advanced metastatic prostate cancer by preventing the cancer from using testosterone to fuel its growth. Additionally, this study is using a new type of MRI called a multiparametric MRI (mpMRI) to more accurately pinpoint and assess the significance of the prostate cancer. The mpMRI uses three types of imaging as opposed to one to gain a more complete picture of the prostate and identify more precisely spots in the prostate where significant cancer is present. The mpMRI will provide the most accurate picture of the cancer's response to the therapy. Participants will receive a biopsy for genetic analysis and an mpMRI before treatment begins. Over the course of six months, participants will take enzalutamide pills daily and receive two goserelin injections. After six months of treatment, another mpMRI will be performed before the patient undergoes a prostatectomy.

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 trial tests the effectiveness of combining three different types of treatments: immunotherapy, chemotherapy, and hormone therapy. The prostvac vaccine is a new immunotherapy agent that uses a virus that has been altered to express the same protein found in tumor cells. As a result, the body becomes capable of recognizing the cancer cells containing this protein and launches an immune response to kill the cancer cells. Docetaxel is a chemotherapy drug for prostate cancer that targets rapidly dividing cells like cancer cells for destruction. Androgen deprivation therapy (ADT) is a type of hormone therapy that lowers the amount of testosterone the body produces in order to stop the growth of cancer. This study aims to discover whether the addition of docetaxel and prostvac to a regimen of ADT proves more effective than ADT alone. This trial contains two study groups on different regimens of docetaxel and prostvac. Both groups will receive four months of ADT before being given any other treatment. One group will receive simultaneous treatment with docetaxel and prostvac, and the other group will receive prostvac followed by docetaxel.  

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.

The purpose of this study is to evaluate the effectiveness, safety, and pharmacokinetics (how a drug moves through the body) of ipatasertib (a type of targeted therapy) plus abiraterone (a type of hormonal, or anti-androgen therapy) and prednisone/prednisolone (a type of steroid) compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC). It is thought that combining ipatasertib with standard of care abiraterone + prednisone/prednisolone might be more effective than taking abiraterone + prednisone/prednisolone alone.

Patients will be randomized to one of two arms:

Arm A Ipatasertib + Abiraterone – each cycle is 28 days

Ipatasertib 400 mg oral tablets are taken (at home) once daily by mouth beginning on Day 1 of Cycle 1.

Abiraterone 1000 mg oral tablets are taken (at home) once daily by mouth, taken on an empty stomach and swallowed whole with water, plus prednisone/prednisolone 5 mg oral tablets are taken (at home) twice daily by mouth.

Arm B Placebo + Abiraterone – each cycle is 28 days

Placebo oral tablets (matched to ipatasertib appearance) are taken (at home) once daily by mouth beginning on Day 1 of Cycle 1.

Abiraterone 1000 mg oral tablets are taken (at home) once daily by mouth, taken on an empty stomach and swallowed whole with water, plus prednisone/prednisolone 5 mg oral tablets are taken (at home) twice daily by mouth.

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 trial is to determine the effect of treatment with enzalutamide and Leuprolide, as opposed to only enzalutamide, on extending the period of time when cancer is not growing and progressing. Enzalutamide is a hormone therapy agent that works by preventing tumor cells from using testosterone necessary for cancer cells to grow. Leuprolide stimulates the brain to produce less testosterone, which can help slow the progression of prostate cancer. Persons eligible for this trial are those whose prostate-specific antigen is rising after either radiotherapy or a prostatectomy. Participants will be randomly separated into three treatment groups. The first group will receive enzalutamide pills for daily use and leuprolide injections every 12 weeks. The second group will receive only enzalutamide pills. The third group will receive a pill for daily use containing an inactive agent and leuprolide injections every 12 weeks. Participants will not know which treatment group they are in.

Sipuleucel-T is a recently approved immunotherapy agent for the treatment of prostate cancer. With this form of immunotherapy, the cells responsible for triggering an immune response tailored to fight a specific pathogen are extracted from a patient's own blood, and a protein found in prostate cancer cells is then introduced. After exposure to the protein, the patient's cells, once inserted back into the patient, are prepared and able to launch a targeted immune response to kill the cancer cells. Radium-223 is a form of IV radiation that targets bone metastases. This trial is designed to test the theory that radium-223, when added to treatment with sipuleucel-T, enhances the body's immune response to the cancer compared to treatment with sipuleucel-T alone. This hypothesis is based on knowledge that radiation, when it kills the cancer cells, releases the proteins that trigger the immune response. Participants will be randomly separated into two treatment groups. Both groups will be treated with three sipuleucel-T injections, with one injection every two weeks. In addition to the sipuleucel-T, one group will also receive radium-223 injections every four weeks for a total of six infusions.

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.  

This trial is not testing a treatment or drug but rather aims to use multiple methods and measures to gain a more holistic and complete view of cancer treatment. Data to be collected include primary factors influencing treatment decisions, treatment patterns (including disease assessment methods), treatment settings and referral patterns, and patients' personal treatment experience both physically and mentally/emotionally. Patients eligible for this trial are those with castration-resistant prostate cancer who are about to start their first course of 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.

The purpose of this study is to evaluate the effectiveness of ProstAtak immunotherapy in patients undergoing active surveillance for localized prostate cancer. ProstAtak involves the use of aglatimagene besadenovec (AdV-tk) to kill tumor cells and stimulate a cancer vaccine effect. Killing tumor cells in an immune-stimulated environment induces the body's immune system to detect and destroy cancer cells. ProstAtak has been well tolerated in previous trials in patients with prostate cancer and other tumor types. Biochemical (prostate-specific antigen), pathologic (metastatic tumors), and immune responses have been demonstrated in newly diagnosed and recurrent prostate cancer. The hypothesis is that ProstAtak can lead to improvement in the clinical outcome for patients with prostate cancer.

Patients will also receive valacyclovir (Valtrex, an anti-viral drug approved by the Food and Drug Administration), which is given to help the study drug ProstAtak work better.

Treatment will be either:

1. ProstAtak will be delivered to the prostate using a trans-rectal ultrasound-guided injection followed by 14 days of oral valacyclovir (taken at home). The second ProstAtak injection will be 2-3 weeks after the first, again followed by 14 days of oral valacyclovir (taken at home), OR

2. A placebo (treatment with no active medicine) will be delivered to the prostate using a trans-rectal ultrasound guided injection followed by 14 days of oral valacyclovir (taken at home). The second placebo injection will be 2-3 weeks after the first, again followed by 14 days of oral valacyclovir (taken at home).

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.

The purpose of this study is to evaluate the efficacy and safety of olaparib (Lynparza, a type of targeted therapy) versus enzalutamide (Xtandi, a type of anti-androgen or hormonal therapy) or abiraterone acetate (Zytiga, a type of anti-androgen or hormonal therapy) in subjects with metastatic castration-resistant prostate cancer who have progressed on prior treatment with a new hormonal agent (anti-androgens like Xtandi, Zytiga ) and have homologous recombination repair gene mutations (a particular type of genetic mutation).

Patients will receive one of three possible treatments:

Olaparib – olaparib is taken orally (at home) at 300 mg twice daily.

Abiraterone – abiraterone is taken orally (at home) at 160 mg once daily.

Enzalutamide – enzalutamide is taken orally (at home) at 1000 mg once daily.

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.

This is a study of pembrolizumab (Keytruda, MK-3475, at type of immunotherapy) in participants with metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC may respond (have anti-tumor activity) when given pembrolizumab even after prior treatment.

Patients MUST be currently taking Enzalutamide (a type of anti-androgen or hormonal therapy).

All patients will receive pembrolizumab 200 mg intravenously (IV) in the clinic once every three weeks for up to two years.

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 study is open to patients with a solid tumor (prostate cancer) that can be measured by CT or bone scan (is metastatic). LOXO-101 is a type of targeted therapy that targets a specific abnormality in cancer tumors. If a tumor has this specific abnormality (the tumor tissue will need to be tested for this abnormality, if it has not already been done), the hypothesis is that LOXO-101 will have anti-tumor effects and my help these tumors shrink.

LOXO-101 100mg will be taken orally (at home) twice daily. Each cycle is 28 days.

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.

This is an open label, non-randomized, Phase I, dose escalation/dose expansion study of PCUR-101 in combination with androgen suppression therapy in the patients with metastatic castration-resistant prostate cancer (mCRPC). The goal of the study is to test the safety and effectiveness of PCUR-101.

PCUR-101 is created in a laboratory in an oil-based formula to be taken orally based on the naturally occurring compound call plumbagin. Plumbagin was initially derived from various plants used in traditional medicine across Asia and Europe. Plumbagin has displayed anti-tumor activities in cells and in animals in the past, and has demonstrated an effect on prostate cancer cells in the laboratory. PCUR-101, the lab created version of plumbagin, will be the study drug in this study.

Despite the use of plant form of the medicine in traditional medicinal therapies, there is little to no experience with the chemically synthesized molecule (the version made in the lab), PCUR-101, in humans. Participants in this study will be the first humans to receive PCUR-101.

Testing in the laboratory and in animals has shown that PCUR-101 combined with drugs that lower testosterone production (hormonal therapy) increased the effect of the drugs together. It is not currently known how the study drug works in the body.

PCUR-101 will be taken orally (at home) at various dose levels throughout the study, starting at 50 mg and escalating to 300 mg depending on the safety and tolerability of the drug.

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

Patients will be randomized to one of four arms:

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

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

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

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

Arm III: Abiraterone + Prednisone + Olaparib

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

Arm IV: Olaparib

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

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

Patients will be randomized to one of two arms:

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

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

This study evaluates the safety, anti-tumor effect, and immunogenicity of enoblituzumab (a type of immunotherapy) given before radical prostatectomy. If shown to be safe, it is hypothesized that enoblituzumab will have an anti-tumor effect (targeting cancer cells not yet visible on CT or bone scans) in men with intermediate and high-risk localized prostate cancer.

Enoblituzumab 15mg/kg will be given intravenously (IV in the clinic) once weekly for six doses beginning 50 days prior to a radical prostatectomy.

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.

The purpose of the study is to assess the effectiveness and safety of BAY1841788 (Darolutamide or ODM-201, a type of hormonal or anti-androgen therapy) in combination with standard androgen deprivation therapy (ADT or hormonal therapy) and docetaxel (chemotherapy) in patients with metastatic hormone sensitive (or castration-resistant) prostate cancer.

If shown to be safe, adding BAY 1841788 / ODM-201 to standard of care ADT and chemotherapy is hypothesized to provide more anti-tumor effect (more tumor shrinkage) than ADT and chemotherapy alone.

Treatment will be either:

1. BAY 1841788 / ODM-201 600 mg taken orally (at home) with food twice daily PLUS standard ADT (luteinizing hormone releasing hormone [LHRH] agonist/antagonist or orchiectomy per local standards) PLUS six cycles of docetaxel given intravenously (IV in the clinic) per local standards, OR

2. Placebo (an inactive drug that visibly matches BAY 1841788/ODM-201) taken orally (at home) with food twice daily PLUS standard ADT (luteinizing hormone releasing hormone (LHRH) agonist/antagonist or orchiectomy per local standards) PLUS six cycles of docetaxel given intravenously (IV in the clinic) per local standards.

The aim of this study is to estimate the PSA response rate with the use of ketoconazole (a type of anti-fungal drug used as standard of care therapy for prostate cancer after progression on anti-androgen therapy) among men with CRPC in whom disease has progressed despite abiraterone (a type of hormonal or anti-androgen therapy). The study has 1 arm: Calcitriol (vitamin D), Ketoconazole, Hydrocortisone (a steroid) Patients take calcitriol by mouth (at home) 10mcg once daily 3 consecutive days per week in addition to ketoconazole by mouth (at home) 400mg once daily and hydrocortisone by mouth (at home) 20mg every morning + 10 mg each evening.

The purpose of this research study is investigate a new and validated urine test which predicts the likelihood of high grade prostate cancer on an initial prostate biopsy (taking a tissue sample of the prostate). The current protocol has two objectives; one is to further assess and evaluate the performance of the urine test in men already scheduled for initial prostate needle biopsy (cohort 1) and two, to evaluate how the results of the urine test influences the decision process for determining whether to perform a prostate biopsy (cohort 2).

Cohort 1

Enroll patients to confirm performance of ExoDx Prostate IntelliScore (EPI) for men scheduled for initial biopsy. The treating physician will collect a urine sample to test before their scheduled prostate biopsy (during a clinic visit).

Cohort 2

Enroll patients to evaluate how the results of the urine test influences the decision process for determining whether to perform a prostate biopsy. The treating physician will collect a urine sample for testing and, 2 weeks later, discuss whether to perform a prostate biopsy (knowing the results of the urine test), and comparing them other clinical factors the treating physician would otherwise use to determine whether they should have a prostate biopsy.

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).

This clinical trial is being conducted to recommend a safe and tolerable phase 2 dose of docetaxel (a type of chemotherapy) or cabazitaxel (a type of chemotherapy) when combined with clarithromycin (a type of antibiotic) in men who have developed castrate-resistant prostate cancer.

In the castrate-resistant setting, resistance to taxane therapy (drugs like docetaxel and cabazitaxel) inevitably develops. Men who develop resistance to taxanes have a very poor prognosis, and few treatment options.

It is believed that CYP enzymes (a particular type of enzyme in the blood) contribute to docetaxel and cabazitaxel resistance in metastatic prostate cancer, and this resistance can be mitigated through pharmacologic CYP inhibition. In this study a potent CYP3A inhibitor (a drug that inhibits the effects of the CYP enzyme in the blood), clarithromycin, will be co-administered concurrently with either docetaxel or cabazitaxel, whose systemic metabolism is dependent of CYP3A4, with the intent to overcome resistance to taxanes.

Patients will be enrolled in one of two arms of the study based on prior treatment they have received:

Arm A: Docetaxel and clarithromycin combination

Docetaxel will be administered by intravenous infusion (in clinic) over 1 hour one every 3 weeks on day 1 of each (3 week) cycle for a total of 18 weeks.

Clarithromycin will be taken orally (at home) at 500mg twice a day for 3 days per cycle on days -1 (the day before the docetaxel infusion), 1, and 2.

Arm B: Cabazitaxel and clarithromycin combination

Cabazitaxel will be administered by intravenous infusion (in clinic) over 1 hour every 3 weeks on day 1 of each (3 week) cycle for a total of 18 weeks.

Clarithromycin will be taken orally (at home) at 500mg twice a day for 3 days per cycle on days -1 (the day before the cabazitaxel infusion), 1, and 2.

The intent of this study is to establish the International Registry to Improve Outcomes in Men with Advanced Prostate Cancer (IRONMAN). The goal is to establish a population-based registry and recruit patients across academic (affiliated with a teaching hospital or medical school) and community practices from Australia, Brazil, Canada, Ireland, Sweden, Switzerland, the United Kingdom (UK), and the US. This cohort study will facilitate a better understanding of the variation in care and treatment of advanced prostate cancer across countries and across academic and community based practices.

Detailed data will be collected from patients at study enrollment and then during follow-up, for a minimum of three years. Patients will be followed for overall survival, clinically significant adverse events, comorbidities (other diseases or illnesses that may arise), changes in cancer treatments, and PROMs (a type of quality of life questionnaire).

PROMs questionnaires will be collected at enrollment, every three months for the first and second year, then every six months.

As such, this registry will help identify the treatment sequences or combinations that optimize overall survival and PROMs (quality of life). By collecting blood at enrollment, time of first change in treatment and/or one year follow-up, this registry will further identify and validate molecular phenotypes (differences based on specific cells in the blood) of disease that predict response and resistance to specific therapeutics. Additionally, every effort will be made to collect blood specimen at each subsequent change in treatment. When feasible, existing tumor tissue may be collected for correlation with described blood based studies. All samples will be used for future research. This cohort study will provide the research community with a unique biorepository (collected of blood and tumor tissue) to identify biomarkers (specific cells in the blood or tumor tissue) of treatment response and resistance.

This randomized phase II/III trial studies docetaxel (a type of chemotherapy), antiandrogen therapy (hormonal therapy), and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery (patients who have had a prostatectomy). Androgen can cause the growth of prostate cells. Anti-hormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. 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 antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells. This study has 2 arms: Arm A: Androgen deprivation therapy +, EBRT (radiation) Patients receive androgen deprivation therapy for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT (radiation) for 7.5 weeks. Arm B: Androgen deprivation therapy + EBRT (radiation) + docetaxel (chemotherapy) Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel intravenously (IV) on day 1 of every 21 days for 6 courses in the absence of disease progression or unexpected toxicity.

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.

This randomized phase II trial studies how well olaparib (Lynparza, a targeted therapy, a PARP inhibitor) with or without cediranib (a type of targeted therapy, an anti-VEGF TKI) works in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Olaparib and cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This study has 2 arms: 1 cycle = 28 days Arm A: Olaparib + Cediranib Patients take olaparib by mouth twice daily + cediranib by mouth once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm B: Olaparib alone Patients take olaparib by mouth twice daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

This randomized phase III trial studies how well decision aids work in improving knowledge in patients with newly diagnosed prostate cancer. Decision aids may improve patients' knowledge of their condition and options for treatment, and may also help when talking with their doctor. The study has 4 arms: Arm A: "Knowing your Options", "Prostate Choice" Patients receive decision aids "Knowing your Options" before and "Prostate Choice" during their consultation visit. Arm B: "Knowing your Options" Patients receive "Knowing your Options" decision aid before their consultation visit. Arm C: "Prostate Choice" Patients receive "Prostate Choice" decision aid during their consultation visit. Arm D: usual care) Patients undergo usual care.

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.