Relugolix + Enzalutamide Study in High-Risk Prostate Cancer

NCT06130995 | Recruiting Phase 1 DMC

• 1 other identifier: OU-SCC-RENAPCA
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test how effective and safe it is to use a combination of two medications, relugolix and enzalutamide, in patients with advanced prostate cancer. We want to see if this combination can help improve the chances of curing the cancer and make the patients live longer without the cancer getting worse. The main questions we want to answer in this study are:

• Can using relugolix and enzalutamide together help increase the chances of curing high-risk advanced prostate cancer?
• Does this combination treatment help patients live longer without their cancer getting worse? Participants in this study will be asked to take relugolix and enzalutamide as part of their cancer treatment. They will also undergo Radiation Therapy or prostatectomy, which are standard treatments for this type of cancer.

Conditions

Androgen Deprivation Therapy; Locally Advanced Prostate Cancer

Keywords

dose limiting toxicity (DLTs); pathologic complete response (pCR); minimal residual disease (MRD); radiation therapy (RT)

Outcome Measures

Primary Outcomes (2)

• Proportion of patient experiencing dose limiting toxicity (DLT) and tolerable dose of relugolix and enzalutamide combination

  Proportion of patients will undergo evaluation for dose-limiting toxicity (DLT) to establish a tolerable dosage regimen for the combined use of relugolix and enzalutamide in individuals diagnosed with high-risk locally advanced prostate cancer. The assessment hinges on identifying DLTs associated with this treatment using 3-12 patients from the safety lead-in cohort and continuously monitoring treatment-related adverse events throughout the DLT observation period, which spans 24 months, encompassing neoadjuvant and adjuvant treatment phases.

  2-3 years

• Proportion of patients experiencing Pathologic Complete Response (pCR) and Minimal Residual Disease (MRD) in Neoadjuvant ADT with the combination of Relugolix and Enzalutamide

  Proportion of patients achieving a pathologic response rate, defined as the combined Pathologic Complete Response (pCR) Rate and Minimal Residual Disease (MRD) rate (MRD, tumor ≤5 mm), serves as the primary endpoint for the dose expansion cohort. This assessment will be conducted using Simon's optimal 2-stage design, enabling a determination of whether there are an adequate number of patients with objective responses to proceed to the second stage of the study (at the interim analysis) or to consider the drug for further investigation in a Phase III study (at the study's conclusion).

  4-6 years

Secondary Outcomes (5)

• Objective response rate (ORR) of neoadjuvant ADT of relugolix and enzalutamide

  4-6 years

• Frequency and severity of adverse events of relugolix and enzalutamide

  4 years

• Prostate specific antigen (PSA) response to the combination of relugolix and enzalutamide

  4 years

• Diagnostic precision and constraints of biopsy in assessing positive margin rates and rates of pathologic downgrade.

  4-6 years

• Progression-Free Survival (PFS) in Patients Receiving Neoadjuvant Relugolix and Enzalutamide

  4-6 years

Study Arms (1)

Prostate Cancer Combo Therapy Trial

EXPERIMENTAL

A single-arm Phase Ib study explores the effectiveness and safety of neoadjuvant and adjuvant hormonal therapy combining relugolix and enzalutamide in high-risk locally advanced prostate cancer patients eligible for ADT followed by radiation therapy or surgery.

Drug: Relugolix and Enzalutamide

Interventions

Relugolix and Enzalutamide DRUG

Dose level of Relugolix and Enzalutamide Safety Lead-in Cohort, 3-12 patient. Relugolix;120 mg, oral, once daily, with a loading dose of 360 mg on day 1, Enzalutamide; 120-160 mg, oral, once daily. Dose Expansion Cohort, up to 34 patients. Relugolix;120 mg, oral, once daily, with a loading dose of 360 mg on day 1, Enzalutamide; To be determined by safety lead-in cohort. One cycle = 3 months The dose limiting toxicity (DLT) period is the first 28 days Neoadjuvant ADT: 6 months; Relugolix: 120 mg orally, daily (with a 360 mg loading dose on day 1, Enzalutamide: 160 mg (or 120 mg) orally, daily Concurrent ADT during Radiation Therapy; Relugolix: 120 mg orally, daily (with a 360 mg loading dose on day 1, Enzalutamide: 160 mg (or 120 mg) orally, daily Maintenance ADT: Additional 18 months; Relugolix: 120 mg orally, daily (with a 360 mg loading dose on day 1, Enzalutamide: 160 mg (or 120 mg) orally, daily

Prostate Cancer Combo Therapy Trial

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent;
• Patients must be ≥18 years of age at the time of signing the informed consent form.
• Men with a diagnosis of adenocarcinoma of the prostate pathologically proven diagnosis with the following:
• Locally advanced high-risk prostate defined as i. PSA \>20 ng/mL or ISUP grade 4/5 (Gleason score \>7) or cT2c or ii. Any PSA, any ISUP grade, cT3-4 or cN+ (locally advanced)
• Have normal organ and bone marrow function measured at the screening visit including
• Platelets ≥100 × 103/microliter (μL);
• Hemoglobin ≥ 10.0 grams/dL;
• Leukocytes (WBC) ≥ 3 × 103/μL;
• Absolute neutrophil count ≥1.5 × 103/μL;
• Serum AST and ALT ≤2.5 × upper limit of normal (ULN);
• Total bilirubin ≤1.5 ×ULN (unless values are consistent with Gilbert's syndrome for which the total bilirubin must be \< 3x ULN);
• Serum creatinine ≤ 1.5 × ULN; OR Measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• The participant has, in the opinion of the investigator, a life expectancy of at least 6 months.
• Male patients must be willing to use contraception during treatment and for 3 months after the last dose of study treatment when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

You may not qualify if:

• History of major adverse cardiac event, including myocardial infarction, new congestive heart failure (CHF) or CHF exacerbation, or stroke, within the past 6 months.
• Patients who are receiving any other investigational agents.
• Patients with distant metastatic cancer will be excluded from the study as intermittent hormonal therapy is not standard of care treatment for this population.
• Active secondary malignancies requiring treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of study drugs
• Participants with uncontrolled intercurrent illness.
• Participant is unable to swallow pills.
• Not a candidate for surgical or radiation therapy

Sponsors & Collaborators

• University of Oklahoma: lead
• Pfizer: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (1)

Stephenson Cancer Center at OU Health, University of Oklahoma Health Sciences Center (SCC-OUHSC)

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

MeSH Terms

Conditions

Pathologic Complete Response; Neoplasm, Residual

Interventions

relugolix; enzalutamide

Condition Hierarchy (Ancestors)

Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Neoplasms

Central Study Contacts

lead onco nurse, RN

CONTACT

405-271-8777; SCCIITOffice@ouhsc.edu

Kelly Stratton, MD

CONTACT

(405) 271-6900; Kelly-Stratton@ouhsc.edu

Study Design

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

Model Details: This is a single arm phase Ib study with safety lead-in cohorts to investigate the efficacy and safety of neoadjuvant and adjuvant hormonal therapy with relugolix plus enzalutamide in patients with high-risk locally advanced prostate cancer who are candidates for ADT followed by definitive radiation therapy (RT) or surgical treatment.

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 14, 2023
• Study Start: December 26, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)