PRIMARY OBJECTIVES:
I. To compare the progression free survival (PFS) between standard of care (SOC) + MDRT (Arm 1A) versus (vs) SOC alone (Arm 1B). (Cohort 1 \[cytotoxic therapy cohort\]) II. To compare the proportions of patients in Arm 2A vs Arm 2B who attain complete response (CR) 6 months after randomization. (Cohort 2 \[non-cytotoxic therapy cohort\])
SECONDARY OBJECTIVES:
I. To compare the radiographic progression-free survival (rPFS) between Arms 1A and 1B. (Cohort 1 \[cytotoxic therapy cohort\]) II. To determine the proportions of patients with metastatic hormone sensitive prostate cancer (mHSPC) who achieve a serum prostate-specific antigen (PSA) level \< 4 ng/mL and \< 0.01 ng/mL and compare them between Arm 1A and 1B. (Cohort 1 \[cytotoxic therapy cohort\]) III. To determine the proportion of patients with skeletal related events (SRE), and compare them between Arms 1A and 1B. (Cohort 1 \[cytotoxic therapy cohort\]) IV. To assess the safety and toxicity of MDRT during and following MDRT completion. (Cohort 1 \[cytotoxic therapy cohort\]) V. To determine the objective response rate (ORR), defined as the proportion of patients who experience a confirmed complete response (CR) or confirmed partial response (PR) on fludeoxyglucose F-18 (FDG)-PET-2, and to compare ORR between Arms 2A and 2B. (Cohort 2 \[non-cytotoxic therapy cohort\]) VI. To determine the progression-free survival (PFS) and radiographic progression-free survival (rPFS), and to compare between Arms 2A and 2B. (Cohort 2 \[non-cytotoxic therapy cohort\]) VII. To determine the proportions of patients with mHSPC who achieve a serum PSA level \< 4 ng/mL and \< 0.01 ng/mL (undetectable), and compare them between Arms 2A and 2B. (Cohort 2 \[non-cytotoxic therapy cohort\]) VIII. To determine the proportion of patients with skeletal related events (SRE), and compare them between Arms 2A and 2B. (Cohort 2 \[non-cytotoxic therapy cohort\]) IX. To assess the safety and toxicity of MDRT during and following MDRT completion. (Cohort 2 \[non-cytotoxic therapy cohort\])
EXPLORATORY OBJECTIVES:
I. To examine association between imaging features and progression free survival (Cohort 1) or likelihood of response (Cohort 2).
II. To determine the time to treatment discontinuation (TTD) in Cohort 1 Arm 1A, 1B, and 1C, and Cohort 2 Arms 2A, 2B and 2C.
OUTLINE: Patients undergoing cytotoxic chemotherapy are assigned to Cohort 1, while patients not undergoing cytotoxic chemotherapy are assigned to Cohort 2.
COHORT 1: Patients undergo an FDG-PET scan after 6 months of SOC cytotoxic chemotherapy + androgen deprivation therapy (ADT). Patients with PET-avid disease are randomized to Arm 1A or 1B. Patients without PET-avid disease are assigned to Arm 1C.
ARM 1A: Patients continue their SOC ADT and undergo MDRT to up to 5 disease sites in the absence of unacceptable toxicity. Patients also undergo computed tomography (CT) and bone scans throughout the trial.
ARM 1B: Patients continue their SOC ADT on study. Patients also undergo CT and bone scans throughout the trial.
ARM 1C: Patients continue their SOC ADT on study. Patients also undergo CT and bone scans throughout the trial.
COHORT 2: Patients undergo an FDG-PET scan after 6 months of SOC ADT. Patients with PET-avid disease are randomized to Arm 2A or 2B. Patients without PET-avid disease are assigned to Arm 2C.
ARM 2A: Patients continue their SOC ADT and undergo MDRT to up to 5 disease sites in the absence of unacceptable toxicity. Patients undergo an additional FDG-PET scan at 6 months. Patients also undergo CT and bone scans throughout the trial.
ARM 2B: Patients continue their SOC ADT on study and undergo an additional FDG-PET scan at 6 months. Patients also undergo CT and bone scans throughout the trial.
ARM 2C: Patients continue their SOC ADT on study and undergo an additional FDG-PET scan at 6 months. Patients also undergo CT and bone scans throughout the trial.
After completion of study treatment, patients are followed up at 3 months (Arms 1A, 1B, 2A, 2B only) and 6 months, and then every 6 months until 36 months.
