Schedule De-Escalation of 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer

PRIMARY OBJECTIVES: I. To determine whether composite progression-free survival (PFS) per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, by physician discretion on prostate specific membrane antigen (PSMA)-positron emission tomography (PET), or biochemical progression is non-inferior among patients randomized to treatment pause versus standard treatment in patients with metastatic castrate resistant prostate cancer (mCRPC) who have minimal residual disease on post-therapy single photon emission computed tomography (SPECT) after 2 to 5 cycles of 177Lu-PSMA-617 treatment. SECONDARY OBJECTIVES: I. To compare time to subsequent treatment (TTST) in this patient population between randomized arms. II. To assess time to radiographic progression per PCWG3-modified RECIST 1.1 or by physician discrection on PSMA PET between randomized arms in this patient population between randomized arms. III. To assess overall survival (OS) in this patient population between randomized arms. IV. To compare toxicities in treatment pause versus standard treatment in this patient population. V. To assess changes in patient quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACIT-RNT) for each randomized arm. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive 177Lu-PSMA-617 intravenously (IV) over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive 68Ga-prostate specific membrane antigen-11 (gallium Ga 68-labeled PSMA-11) IV and undergo positron emission tomography (PET)/computed tomography (CT) during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial. ARM II: Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial. ARM III: Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial. After completion of study treatment, patients are followed up every 12 weeks for up to 2 years or progressive disease.