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

Official title

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.

Overview

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.

Interventions

• Drug Androgen Deprivation Therapy (ADT)
  ADT, Gonadotropin-releasing hormone (GnRH) agonist or antagonists, as prescribed by the treating physician.
• Drug Androgen Receptor Pathway Inhibitor (ARPI)
  Darolutamide is the preferred ARPI for this study; however, patients may receive abiraterone, apalutamide, or enzalutamide at the discretion of their oncologist and based on patient preference.
• Radiation Prostate Radiation
  prostate radiation, with or without radiation to metastatic sites
• Drug Docetaxel
  Docetaxel will be administered as prescribed by the treating physician.

Primary outcome measures

• Radiological progression-free survival (rPFS) [Time frame: 36 months]

Secondary outcome measures (12)

• Overall survival (OS) [Time frame: 5 years]
• rPFS using PSMA PET/CT scan combined with PSA response [Time frame: 5 years]
• Time to initiation of subsequent antineoplastic therapy [Time frame: 5 years]
• Disease progression within 5 years of starting ADT for mCSPC [Time frame: 5 years]
• Symptomatic skeletal event free (SSE) survival [Time frame: 5 years]
• Time to pain progression [Time frame: 5 years]
• Adverse Events [Time frame: 5 years]
• Quality-of-life changes per Functional Assessment of Cancer Therapy (FACT) Prostate Cancer Symptom Index - 17 (FACT-FPSI-17) [Time frame: 3 months, 6 months, 9 month, 1 year]
• Quality-of-life changes per Brief Pain Inventory-Short Form (BPI-SF) [Time frame: 3 months, 6 months, 9 month, 1 year]
• Development of osteoporosis [Time frame: 5 years]
• Development of osteopenia [Time frame: 5 years]
• Prevalence of gynecomastia [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• 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.

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

Exclusion criteria

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

• Chemotherapy other than docetaxel for prostate cancer any time prior to enrollment;
• Radiopharmaceuticals for prostate cancer any time prior to enrollment.
• Patients who have received treatment with radiotherapy (EBRT, brachytherapy, or radiopharmaceuticals) within 2 weeks before prior to the start of study treatment.
• 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.

• 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).
• Patients with an inability to swallow oral medications in the opinion of the clinical investigator.
• Patients with leptomeningeal disease.

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Georgetown University Medical Center- Lombardi Comprehensive Cancer Center — Washington D.C.

Identifiers

NCT: NCT07645326 · STUDY00010158

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗