A Phase 2 Trial of ADT Interruption in Patients Responding Exceptionally To AR-Pathway Inhibitor in Metastatic Hormone-Sensitive Prostate Cancer (MHSPC): A-DREAM

This phase II trial examines antiandrogen therapy interruptions in patients with
hormone-sensitive prostate cancer that has spread to other places in the body
(metastatic) responding exceptionally well to androgen receptor-pathway inhibitor
therapy. The usual treatment for patients with metastatic prostate cancer is to receive
hormonal medications including a medication to decrease testosterone levels in the body
and a potent oral hormonal medication to block growth signals from male hormones (like
testosterone) in the cancer cells. Patients whose cancer is responding exceptionally well
to this therapy may take a break from these medications according to their doctor's
guidance. This trial may help doctors determine if stopping treatment can allow for
testosterone recovery.

Inclusion Criteria:

- Histologic or clinical diagnosis of metastatic prostate cancer

- Must have had evidence of metastatic disease by bone scan, or nodal or visceral
lesions on computed tomography (CT) or magnetic resonance imaging (MRI) prior to
starting 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 variant
disease biology for which intermittent treatment may not be favored

- Must currently be receiving intense ADT for metastatic hormone sensitive prostate
cancer (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) from
time of first dose of LHRH agonist or antagonist by time of registration. A period
of anti-androgen treatment prior to LHRH agonist or antagonist initiation is not
included 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 of
A032101 registration. Treatment breaks from ARPI of up to 28 days are permitted (for
example peri-procedural or for management of a temporary adverse event) as long as
PSA did not rise while holding therapy

- Prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with local
therapy is permitted. Prior course(s) of intermittent TS for biochemical-only
recurrence is permitted. However, if the patient previously received TS, metastatic
progression for which intense ADT was initiated must have occurred during an
off-treatment interval and with testosterone >= 150 ng/dL

- Prior local therapy for prostate cancer (either before or after diagnosis of
metastatic disease) is permitted. Prior treatment with docetaxel chemotherapy for up
to 6 cycles is permitted. Prior radiation therapy to metastatic sites (either for
symptom 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 is
currently receiving intense ADT (such as in the neoadjuvant setting with prior local
therapy)

- No current or prior treatment with experimental agents for metastatic
hormone-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 was
not measured prior to initiating intense ADT for mHSPC if they did not
previously receive TS and were not known or suspected to be hypogonadal at the
time

- At time of enrollment to A032101

- PSA < 0.2 ng/ml

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

- Testosterone < 50 ng/dl

- No current participation in a clinical study that does not allow for TS or ARPI
interruption

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