Optimal PSA Triggered Individual Management of Androgen Sensitive Prostate Cancer

Official title

A Phase II Randomized, Decentralized, De-escalation Study in Patients With Metastatic Hormone-Sensitive Prostate Cancer Achieving Optimal PSA Response (OPTIMAS)

Overview

The purpose of this study is to evaluate intermittent relugolix + androgen receptor pathway inhibitor (ARPI) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) achieving optimal PSA response.

Interventions

• Drug relugolix + ARPI
  Step 1: Continuous treatment with relugolix + ARPI
• Drug Intermittent- Relugolix or androgen deprivation therapy (ADT) + ARPI
  Intermittent treatment with relugolix + ARPI.
• Drug relugolix or androgen deprivation therapy (ADT) + ARPI
  Step 2: Standard-of-care, continuous treatment with relugolix or androgen deprivation therapy (ADT) + ARPI.
• Drug relugolix + ARPI.
  Step 2: Intermittent treatment with relugolix + ARPI.

Primary outcome measures

• Cohort A: Brief Fatigue Inventory (BFI) score 6 months after randomization. [Time frame: 6 months]
• Cohort B: Progression-free survival (PFS) as defined as the time from intermittent study initiation (first treatment break) to the time of documented disease progression or death from any cause at one year. [Time frame: 12 months]

Secondary outcome measures (12)

• Changes in health-related quality of life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQC30). [Time frame: 13 months]
• Changes in health-related quality of life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQ-PR25). [Time frame: 13 months]
• Sexual function improvement in those with intact sexual function at baseline as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire. [Time frame: 13 months]
• Changes in severity of hot flashes as measured by the Hot Flash Related Daily Interference Scale (HFRDIS). [Time frame: 13 months]
• Changes in cognitive function as measured by the PROMIS-Cognitive function Short Form 8a. [Time frame: 13 months]
• Change from baseline over time in each PRO, including time to recovery and deterioration in the intermittent arm with treatment break and start. [Time frame: 2 years]
• Time to metastatic castration-resistant prostate cancer. [Time frame: 12 months]
• Overall survival and prostate cancer-specific survival at 3 years from the date of randomization. [Time frame: 12 months]
• Time to systemic treatment change. [Time frame: 12 months]
• Duration of time on treatment [Time frame: 12 months]
• Time to first treatment restart [Time frame: 12 months]
• Duration of time with testosterone < 50 ng/mL [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

Cohort A Eligibility (Step 1 Registration)

• Participant aged ≥ 18 years
• Hormone-sensitive prostate cancer with histologically/cytologically confirmed adenocarcinoma without small cell histology.
• Metastasis detected any time prior to study registration on conventional or functional imaging as determined by the treating investigator and can be of any site.
• Baseline testosterone >50 ng/dl before start of therapy for metastatic disease
• PSA ≥ 1 ng/mL before start of therapy for metastatic disease
• ECOG Performance Status ≤ 2
• Eligible to receive standard of care treatment with relugolix and APRI per clinical investigator.
• Participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception requirements as described in Section 5.5.1.

• If the risk of seminal transfer from the participant is present, the participant must agree to use a condom during sexual intercourse as described in Section 5.5.2.
• Participants must agree not to donate sperm from the start of study therapy until 3 months after the last dose of study therapy.
• Clinically significant adverse effects from any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy) must have resolved or have been determined to be clinically stable per the Investigator.
• Has access to a smartphone and wireless services and is able to download and navigate study specific applications.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Cohort A Eligibility (Step 2 Registration) -PSA ≤ 0.2 ng/mL after 6-12 months of relugolix and androgen receptor pathway inhibitor treatment. Androgen receptor pathway inhibitor includes abiraterone, enzalutamide, apalutamide, darolutamide or similar drugs.

Cohort B Eligibility

• Participant aged ≥ 18 years
• Hormone-sensitive prostate cancer with histologically/cytologically confirmed adenocarcinoma without small cell histology.
• Metastasis detected any time prior to study registration on conventional or functional imaging as determined by clinical investigator and can be of any site.
• PSA ≤ 0.2 ng/mL after treatment with androgen deprivation therapy or androgen receptor pathway inhibitor treatment or both of any duration. Androgen deprivation therapy in this context includes gonadotropin-releasing hormone agonists and antagonists. Androgen receptor pathway inhibitors include abiraterone, enzalutamide, apalutamide, darolutamide or similar drugs.
• Eligible to receive standard of care treatment with relugolix and APRI per clinical investigator.
• Participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception requirements as described in Section 5.5.1.

• If the risk of seminal transfer from the participant is present, the participant must agree to use a condom during sexual intercourse as described in Section 5.5.2.
• Participants must agree not to donate sperm from the start of study therapy until 3 months after the last dose of study therapy.
• Has access to a smartphone and wireless services and is able to download and navigate study specific applications.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion criteria

Cohort A Eligibility (Step 1 Registration)

• Participant received androgen deprivation therapy (defined as leuprolide or surgical castration) for metastatic hormone-sensitive prostate cancer.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
• Known brain metastases or cranial epidural disease.

--Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically stable and receiving a stable or decreasing corticosteroid dose at the time of study entry.

• Current evidence of uncontrolled, significant intercurrent illness, infection, non-compliance or other safety concerns which may affect clinical trial participation.
• Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v5.0 Grade ≥ 3).
• Participants taking prohibited medications as described in Section 6.6.2.

Cohort A Eligibility (Step 2 Registration)

• Receiving other systemic anti-cancer therapy for prostate cancer. Prior treatment before Step 2 registration is allowed.
• Progression to metastatic castration-resistant prostate cancer per clinical investigator.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
• Participants taking prohibited medications as described in Section 6.6.2.

Cohort B Eligibility

• Receiving other systemic anti-cancer therapy for prostate cancer.
• History of surgical castration.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
• Known brain metastases or cranial epidural disease.

--Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically stable and receiving a stable or decreasing corticosteroid dose at the time of study entry

• Current evidence of uncontrolled, significant intercurrent illness, infection, compliance or other safety concerns which may affect clinical trial participation.
• Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v5.0 Grade ≥ 3).
• Participants taking prohibited medications as described in Section 6.6.1.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Huntsman Cancer Institute at University of Utah — Salt Lake City

Identifiers

NCT: NCT07216248 · HCI194008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗