Testing Interruption of Hormonal Medications in Patients Responding Exceptionally to Therapy for Metastatic Prostate Cancer, (A-DREAM)

Inclusion Criteria:

• Histologic or clinical diagnosis of metastatic prostate cancer

• Must have had evidence of metastatic disease by bone scan, or nodal or viscerallesions on computed tomography (CT) or magnetic resonance imaging (MRI) prior tostarting on intense antiandrogen therapy (ADT)

• Radiographic evidence of disease is not required at the time of enrollment

• No metastases to liver or to brain, as these represent aggressive variantdisease biology for which intermittent treatment may not be favored

• Must currently be receiving intense ADT for metastatic hormone sensitive prostatecancer (mHSPC)

• Testosterone suppression (TS) with luteinizing hormone releasing hormone (LHRH)-agonist or LHRH-antagonist AND

• An approved secondary androgen receptor pathway inhibitor (ARPI) abiraterone,enzalutamide, or apalutamide (or darolutamide if approved for this indication)

• Must have remained on testosterone suppression for metastatic disease continuously (without treatment breaks) for 540-750 days (approximately 18 to 24 months) fromtime of first dose of LHRH agonist or antagonist by time of registration. A periodof anti-androgen treatment prior to LHRH agonist or antagonist initiation is notincluded in the 540 - 750 days (approximately 18 to 24 months)

• Must have received treatment with ARPI for at least 360 days in total by time ofA032101 registration. Treatment breaks from ARPI of up to 28 days are permitted (forexample peri-procedural or for management of a temporary adverse event) as long asPSA did not rise while holding therapy

• Prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with localtherapy is permitted. Prior course(s) of intermittent TS for biochemical-onlyrecurrence is permitted. However, if the patient previously received TS, metastaticprogression for which intense ADT was initiated must have occurred during anoff-treatment interval and with testosterone >= 150 ng/dL

• Prior local therapy for prostate cancer (either before or after diagnosis ofmetastatic disease) is permitted. Prior treatment with docetaxel chemotherapy for upto 6 cycles is permitted. Prior radiation therapy to metastatic sites (either forsymptom palliation or for ablation of oligometastatic disease) is permitted

Exclusion Criteria:

• No history of surgical castration

• No history of ARPI use prior to diagnosis of mHSPC for which the patient iscurrently receiving intense ADT (such as in the neoadjuvant setting with prior localtherapy)

• No current or prior treatment with experimental agents for metastatichormone-sensitive prostate cancer

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Prior to initiating intense ADT

• Prostate specific antigen (PSA) >= 5 ng/ml

• Testosterone >= 150 ng/dl. Patients are permitted to enroll if testosterone wasnot measured prior to initiating intense ADT for mHSPC if they did notpreviously receive TS and were not known or suspected to be hypogonadal at thetime

• At time of enrollment to A032101

• PSA < 0.2 ng/ml ** PSA values (measured in the same laboratory) must be stable or falling for 3consecutive measurements - i.e. any PSA rise must be followed by a decrease inPSA that is further decreased or stable on a 3rd measurement. Any patient with 2 consecutive rises in PSA values since achieving castrate level oftestosterone is not eligible

• Testosterone < 50 ng/dl

• No current participation in a clinical study that does not allow for TS or ARPIinterruption

• No patients with a "currently active" second malignancy * Patients withnon-melanomatous skin cancer, superficial bladder cancer, cancer not needing activetherapy for at least 2 years, cancer for which the treating investigator deems thesubject