Advanced Physician Search: 1st Line Therapy

This phase III trial compares the effect of adding docetaxel to hormonal therapy and apalutamide versus hormonal therapy and apalutamide alone in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT), uses surgery or drugs to lower the levels of male sex hormones in a man’s body. This helps slow the growth of prostate cancer. Apalutamide 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. Giving docetaxel in addition to the usual treatment of hormonal therapy and apalutamide may work better in treating patients with metastatic prostate cancer than the usual treatment alone.

Drug: Androgen Therapy, Drug: Apalutamide, Drug: Docetaxel, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Bone Scan, Procedure: PSMA PET Scan, Procedure: Biospecimen Collection, Other: Questionnaire Administration

The purpose of the study is to assess and evaluate dosimetry, safety, and tolerability following administration of up to 12 cycles of (177Lu) vipivotide tetraxetan (also referred to as [177Lu]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter identified as AAA617) in taxane-naïve adult participants with PSMA-positive mCRPC who progressed on a prior ARPI treatment with normal renal function or mild renal impairment (eGFR ≥ 60ml/min).

Drug: AAA617, Drug: Gonadotropin-releasing hormone (GnRH) analogues, Drug: Gonadotropin-releasing hormone (GnRH) antagonists

This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer). A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested. Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.

Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Apalutamide, Procedure: Computed Tomography, Drug: Degarelix, Radiation: External Beam Radiation Therapy, Other: Fluciclovine F18, Drug: Goserelin Acetate, Procedure: Intensity-Modulated Proton Therapy, Radiation: Intensity-Modulated Radiation Therapy, Drug: Leuprolide Acetate, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: Relugolix, Radiation: Stereotactic Body Radiation Therapy, Drug: Triptorelin, Radiation: Volume Modulated Arc Therapy