RISK-ADAPT Protocol in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

A Pragmatic Phase 2 Trial of Risk-Adapted Treatment Approaches Including Treatment De-escalation to Minimize Adverse Effects of Hormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.

This is a prospective, interventional, non-randomized, phase 2 study to assess oncologic outcomes of metastatic hormone-sensitive prostate cancer (mCSPC) patients who receive a risk-adapted treatment approach followed by treatment de-escalation at the Medstar Health network. A pragmatic design will be implemented in order to make the study available to patients at greatest needs from minority populations in the community. Additional assessments include quality-of-life (QoL) and sexual function changes as well as correlative studies. A maximum of 108 patients will be enrolled in this study. The investigators hypothesize that with a risk-adapted treatment approach followed by treatment de-escalation, more than 50% of patients will have radiographic progression-free survival (rPFS) at 36 months. Additionally, the investigators hypothesize that the risk-stratified de-escalation approach will result in fewer treatment-related adverse events and better QoL, compared to historical controls.

Inclusion Criteria:

1. Adult patients with metastatic castrate sensitive prostate cancer that are eligible for standard of care (SOC) per treating physician.

   a. Low risk SOC: ADT + ARPI + radiation to the prostate i. For patients with low-risk disease (defined in Section 8.1), prior treatment with ADT or ARPI for up to 8 weeks for mCSPC is permitted; however, prior treatment with docetaxel is not allowed.

   b. High risk SOC: ADT + ARPI +/- docetaxel i. For patients with high-risk disease (defined in Section 8.1), prior treatment with ADT, ARPI, or docetaxel for up to 8 weeks for mCSPC is permitted.

2. Patients who can give informed consent and are willing to comply with follow-up visits and treatment plans.

Exclusion Criteria:

1. Patients for whom, in the opinion of the investigator, participation in the study, use of the drugs outlined in the study, or use of the risk-adapted treatment de-escalation strategy is not appropriate or safe.

2. Patients who have received prior treatment with any of the following:

   1. Chemotherapy other than docetaxel for prostate cancer any time prior to enrollment;
   2. Radiopharmaceuticals for prostate cancer any time prior to enrollment.

3. Patients who have received treatment with radiotherapy (EBRT, brachytherapy, or radiopharmaceuticals) within 2 weeks before prior to the start of study treatment.

4. Patients with prior treatment with an ARPI for non-metastatic disease within 6 months of diagnosis of metastatic disease are not eligible.

   a. Note: Patients who were diagnosed with metastatic disease or more than 6 months after treatment with an ARPI non-metastatic disease are eligible.

5. Patients who had previous (within 28 days before the start of study drug or 4 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).

6. Patients with an inability to swallow oral medications in the opinion of the clinical investigator.

7. Patients with leptomeningeal disease.