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

NCT07645326 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: STUDY00010158
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

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. We 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, we hypothesize that the risk-stratified de-escalation approach will result in fewer treatment-related adverse events and better QoL, compared to historical controls.

Conditions

Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Outcome Measures

Primary Outcomes (1)

• Radiological progression-free survival (rPFS)

  rPFS is defined as the time from the first dose of systemic therapy for mCSPC to the first documented radiological progression in soft tissue or bone, based on CT, MRI, or NM bone scan, using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) for soft-tissue metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases, or death from any cause.

  36 months

Secondary Outcomes (12)

• Overall survival (OS)

  5 years

• rPFS using PSMA PET/CT scan combined with PSA response

  5 years

• Time to initiation of subsequent antineoplastic therapy

  5 years

• Disease progression within 5 years of starting ADT for mCSPC

  5 years

• Symptomatic skeletal event free (SSE) survival

  5 years

Study Arms (2)

Low Risk Prostate Cancer

EXPERIMENTAL

Low risk patients will receive 6-month doublet therapy with Androgen Deprivation Therapy (ADT) + Androgen Receptor Pathway Inhibitor (ARPI) + prostate radiation with or without radiation to metastatic sites followed by 30 months ARPI monotherapy. At a 36-month timepoint, those who maintain a prostate specific antigen (PSA) ≤ 0.2ng/mL will have the option to either discontinue treatment proceeding with active surveillance or continue on their ARPI until disease progression or intolerable toxicity. Patients who discontinue ARPI will resume ARPI and ADT when the PSA ≥ 2 ng/mL above the lowest PSA on two consecutive checks at least 1 month apart, there is evidence of progressive disease (PD) on conventional scans \[CT/MRI imaging per modified RECIST 1.1 or bone scan per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)\], clinical symptoms of progression, or if the patient prefers to continue ARPI and ADT.

Drug: Androgen Deprivation Therapy (ADT); Drug: Androgen Receptor Pathway Inhibitor (ARPI); Radiation: Prostate Radiation

High Risk Prostate Cancer

EXPERIMENTAL

High-risk patients will receive triplet therapy with ADT + ARPI + 6 cycles of docetaxel followed by 18-months of ADT + ARPI and then 12-month ARPI monotherapy. If a patient has high-risk disease but, based on the investigator's judgment, has contraindications to docetaxel or is deemed unsuitable for it, they will receive the same treatment regimen as other high-risk patients minus the docetaxel. Then at a 36-month timepoint, those who maintain a PSA ≤ 0.2ng/mL will have the option to either discontinue treatment with active surveillance or continue ARPI until disease progression or intolerable toxicity. Patients who discontinue ARPI will resume ARPI and ADT when the PSA ≥ 2 ng/mL above the lowest PSA (nadir) on two consecutive checks at least 1 month apart, there is evidence of progressive disease (PD) on conventional scans \[CT/MRI imaging per modified RECIST 1.1 or bone scan per PCWG3\], clinical symptoms of progression, or if the patient prefers to continue ARPI and ADT.

Drug: Androgen Deprivation Therapy (ADT); Drug: Androgen Receptor Pathway Inhibitor (ARPI); Drug: Docetaxel

Interventions

Androgen Deprivation Therapy (ADT) DRUG

ADT, Gonadotropin-releasing hormone (GnRH) agonist or antagonists, as prescribed by the treating physician.

High Risk Prostate Cancer; Low Risk Prostate Cancer

Androgen Receptor Pathway Inhibitor (ARPI) DRUG

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.

High Risk Prostate Cancer; Low Risk Prostate Cancer

Prostate Radiation RADIATION

prostate radiation, with or without radiation to metastatic sites

Low Risk Prostate Cancer

Docetaxel DRUG

Docetaxel will be administered as prescribed by the treating physician.

Also known as: Taxotere, Docivyx, Docefrez, BEIZRAY

High Risk Prostate Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Georgetown University: lead
• Lantheus Medical Imaging: collaborator

Study Sites (1)

Georgetown University Medical Center- Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Interventions

Androgen Antagonists; Docetaxel

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Paul D Leger, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul D Leger, MD

CONTACT

202-444-2223; paul.d.leger@gunet.georgetown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2032
• Study Completion (Estimated): August 1, 2032
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

US (1)