Metastatic Castration-Resistant Prostate Adenocarcinoma

This phase II trial tests how well Pluvicto works in treating African American patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has continued to grow and spread despite the surgical removal of the testes or medical intervention to block androgen production (castration-resistant). Pluvicto is a targeted radioligand therapy. It works like a guided missile, combining tumor seeking molecules with a radioactive isotope. It circulates through the bloodstream, binds to a protein on prostate cancer cells called prostate specific membrane antigen, and destroys them using radiation. Pluvicto is approved by the Food and Drug Administration for the treatment of metastatic castration-resistant prostate cancer. This trial may help researchers determine the safety and efficacy of Pluvicto specifically in African American patients with metastatic castration-resistant prostate cancer.

This phase II/II trial compares the effect of high dose testosterone followed by darolutamide with the usual care in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and keeps growing even when the amount of testosterone in the body is reduced to very low levels (castration-resistant). Usual care treatment for patients with metastatic prostate cancer includes surgery or medical castration which involves drugs to suppress the function of the testes. After receiving this therapy, a period of disease stability occurs, followed typically by cancer regrowth and castration-resistant disease. Castration-resistant prostate cancer occurs because the tumor cells are eventually able to adapt to the very low levels of testosterone in the body. A new type of therapy called Bipolar Androgen Therapy (BAT) involves giving patients very high doses of testosterone every 28 days. This results in a cycle of higher than normal testosterone levels (i.e., "supraphysiologic") to near castrate levels over the 28 days. BAT may be able to stop prostate tumor cells from becoming castrate-resistant. In this trial, patients who receive BAT with high dose testosterone and experience disease progression then receive darolutamide. Darolutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Adding BAT with high dose testosterone prior to darolutamide after disease progression may help shrink or stabilize metastatic castration-resistant prostate cancer better than usual treatments alone.

This phase I trial tests the safety, side effects, best dose and how well giving IL-18 armored STEAP1 CAR T cells after lymphodepleting chemotherapy (with cyclophosphamide and fludarabine) works for the treatment of castration resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Giving chemotherapy, with cyclophosphamide and fludarabine, prior to CAR T cells helps kill cancer cells in the body and prepare the body to receive the CAR T cells. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving IL-18 armored STEAP1 CAR T cells after lymphodepleting chemotherapy may be safe, tolerable and/or effective in treating patients with metastatic castration resistant prostate cancer.

This clinical trial studies whether measuring circulating tumor deoxyribonucleic acid (ctDNA) tumor fraction (TF) can be used to help guide the early stopping (discontinuation) of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) in patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Many types of tumors tend to lose cells or release different types of cellular products including their deoxyribonucleic acid, which is referred to as ctDNA, into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for the disease to grow, spread, or get worse or come back after a period of improvement. ctDNA TF is a type of ctDNA measurement. Research has shown ctDNA TF may be a promising way to predict which patients will respond to 177Lu-PSMA-617 treatment. Measuring ctDNA TF may help doctors identify which patients may benefit from changing treatments sooner, which may be an effective way to guide early 177Lu-PSMA-617 treatment discontinuation in patients with metastatic castration-resistant prostate cancer.

This phase I trial compares the effect of lutetium Lu 177 (177\^Lu)-prostate-specific membrane antigen (PSMA)-617 in combination with Sipuleucel-T to 177\^Lu-PSMA-617 alone in treating patients with prostate that has spread from where it first started (primary site) to other places in the body (metastatic) and has continued to grow and spread despite surgical or medical intervention to block androgen production (castration-resistant). 177\^Lu-PSMA-617, a type of radioconjugate, binds to a protein called PSMA, which is found on some prostate tumor cells. It gives off radiation that may kill the tumor cells. Sipuleucel-T, a type of vaccine and a type of cellular adoptive immunotherapy, is made from immune system cells. The cells are treated with a protein that is made by combining a protein found on prostate tumor cells with a growth factor. When the cells are injected back into the patient, they may stimulate T cells to kill prostate tumor cells. Giving 177\^Lu-PSMA-617 in combination with sipuleucel-T may be safe, tolerable, and/or effective compared to 177\^Lu-PSMA-617 alone in treating patients with metastatic castration-resistant prostate cancer.