Neoadjuvant Darolutamide and Relugolix Combination Preceding Radical Prostatectomy for Prostate Cancer

NCT06631521 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IIR-US-002952077841
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the safety and feasibility of a new combination of darolutamide and relugolix as neoadjuvant therapy preceding radical prostatectomy (RP) for high-risk prostate cancer (PCa) in adult males.

Conditions

Prostate CA; Prostate Cancer (Adenocarcinoma); Prostate Cancer Surgery

Keywords

Prostate Cancer; High-Risk Prostate Cancer; Neoadjuvant Therapy; Radical Prostatectomy; Darolutamide; Relugolix; Androgen Receptor Antagonists; Gonadotropin-Releasing Hormone Antagonists; Clinical Trial Phase I/Ib; PSA Response

Outcome Measures

Primary Outcomes (2)

• Percentage of patients completing therapy without severe adverse events.

  From enrollment, up to 8 weeks after radical prostatectomy.

• Number of patients experiencing treatment-related adverse events using CTCAE version 5.0.

  From enrollment, up to 8 weeks following radical prostatectomy (RP)

Secondary Outcomes (3)

• Objective Radiographic Response

  From enrollment, up to 12 weeks (end of neoadjuvant therapy).

• Prostate-specific antigen (PSA) Response

  From enrollment, up to 8 weeks after radical prostatectomy.

• Plasma Concentration of Darolutamide and Relugolix

  From enrollment, up to Day 1 of Cycle 3 (Each cycle is 28 days).

Study Arms (1)

Combination Therapy Arm

EXPERIMENTAL

This arm is designed to evaluate the safety and feasibility of the combination therapy using darolutamide and relugolix as neoadjuvant treatment before radical prostatectomy (RP) in patients with high-risk prostate cancer (PCa).

Drug: Darolutamide; Drug: Relugolix; Procedure: Radical Prostatectomy

Interventions

Relugolix DRUG

A loading dose of 360 mg on the first day, followed by 120 mg taken orally once daily.

Combination Therapy Arm

Darolutamide DRUG

600 mg (two 300 mg tablets) taken orally twice daily.

Also known as: Nubeqa, BAY 1841788

Combination Therapy Arm

Radical Prostatectomy PROCEDURE

Performed at least 48 hours and within 2 weeks after the completion of neoadjuvant therapy.

Combination Therapy Arm

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• ECOG performance status 0-1
• Ability to swallow oral medications and comply with study procedures and requirements.
• Males ≥18 years
• Participants must have adequate organ and marrow function as below:
• Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L;
• Platelets ≥100,000/mm3 or ≥100 x 109/L;
• Hemoglobin ≥8 g/dL (may have been transfused).
• Estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation.
• Total serum bilirubin \<1.5 x upper limit of normal (ULN), less than 2.0 x ULN if suspected Gilbert's syndrome;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 x ULN.
• Must be a candidate for RP
• Clinical stage cT2-4, N0-1
• Mandatory to identify tumor availability (≥10 FFPE slides, 5 µM thickness \& 1 stained H\&E slide OR tumor block)
• High-risk PCa defined as one of the following-

You may not qualify if:

• Histologic variants including neuroendocrine differentiation, small cell, sarcomatoid, ductal adenocarcinoma, squamous or transitional cell carcinoma) comprising more than 50% of the sample as determined by pathology review
• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to planned cycle 1 day 1 of study treatment.
• Participants who have received anti-neoplastic intervention or experimental antineoplastic therapy within 14 days of planned cycle 1 day 1 of study therapy.
• Participants who are receiving any other investigational agents.
• Participants who have previously received darolutamide, relugolix, LHRH agonist/antagonist or another novel androgen blocking therapy (abiraterone, apalutamide, enzalutamide) within 1 year are excluded (prior bicalutamide that was discontinued ≥14 days prior to planned cycle 1 day 1 is allowed).
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e. have residual toxicities ≥Grade 2) with the exception of alopecia.
• Any of the following within 6 months before planned cycle 1 day 1 of study therapy:
• Stroke
• Myocardial infarction
• Severe/unstable angina pectoris
• Coronary/peripheral artery bypass graft
• Congestive heart failure New York Heart Association (NYHA) Class III or IV.
• Known or suspected contraindications, hypersensitivity or allergy to darolutamide or relugolix or to any of their excipients.
• Participants with hepatitis C, hepatitis B or human immunodeficiency (HIV) who are on anti-viral therapy that has the potential to interact with darolutamide or relugolix.
• Participants treated with drugs known to be strong inhibitors and/or inducers of cytochrome P450 3A4 (CYP3A4) and the treatment cannot be discontinued or switched to a different medication at least 5 half-lives prior to starting study drug.

Sponsors & Collaborators

• AdventHealth: lead
• Bayer: collaborator
• Sumitomo Pharma Switzerland: collaborator

Study Sites (1)

AdventHealth Orlando

Orlando, Florida, 32803, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma

Interventions

darolutamide; relugolix

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Central Study Contacts

AdventHealth Oncology Research

CONTACT

407-303-2090; CFD.ResearchOncology@AdventHealth.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: October 8, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)