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

Alliance for Clinical Trials in Oncology

Status and phase: Active, not recruiting; Phase 2

Conditions: Stage IV Prostate Cancer AJCC v8; Castration-Sensitive Prostate Carcinoma; Stage IVA Prostate Cancer AJCC v8; Metastatic Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8

Treatments: Other: Follow-Up; Other: Pharmacotherapy Discontinuation; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05241860

A032101

NCI-2021-13974 (Registry Identifier)

U10CA180821 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVE:

I. To determine the proportion of men who experience 18-month treatment-free interval from therapy with eugonadal testosterone (to >= 150 ng/ml) after treatment interruption.

SECONDARY OBJECTIVES:

I. To determine time to eugonadal testosterone (> 150 ng/dl). II. To determine duration off-treatment.

III. To assess changes in quality of life as follows:

1. To assess changes in patient-reported quality of life as assessed by the Functional Assessment of Cancer Therapy- Prostate (FACT-P) total score from baseline to 24 months after treatment interruption.
2. To assess changes in the FACT-P subscales (i.e., physical well-being, social and family well-being, emotional well-being, functional well-being, and prostate cancer subscale) from baseline to 24 months after treatment interruption.
3. To assess changes in the FACT-P total score and subscales (i.e., physical well-being, social and family well-being, emotional well-being, functional well-being, and prostate cancer subscale) from baseline to the remaining post-baseline time points (i.e., 6, 12, and 18 months) after treatment interruption.

OUTLINE:

Patients stop both hormonal medications (medication to decrease testosterone levels in the body and potent oral hormonal medication to block growth signals from male hormones in the cancer cells). Patients are then followed every 12 months for symptoms. Patients with an increase in prostate specific antigen (PSA) level to greater than or equal to 5 ng/ml, changes on imaging studies suggesting that their cancer is growing back, or symptoms that the doctor thinks is related to their cancer growing back, resume both hormonal treatments.

After completion of study treatment, patients are followed up every 6 months for 10 years from registration or withdrawal from the study or death.

Enrollment: 79 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

79 participants in 1 patient group

Treatment (discontinue hormonal medication, follow up)

Experimental group

Description:

Patients stop both hormonal medications (medication to decrease testosterone levels in the body and potent oral hormonal medication to block growth signals from male hormones in the cancer cells). Patients are then followed every 12 months for symptoms. Patients with an increase in PSA level to greater than or equal to 5 ng/ml, changes on imaging studies suggesting that their cancer is growing back, or symptoms that the doctor thinks is related to their cancer growing back, resume both hormonal treatments.

Treatment:

Other: Quality-of-Life Assessment

Other: Questionnaire Administration

Other: Pharmacotherapy Discontinuation

Other: Follow-Up