NCT06499870

Relugolix and Enzalutamide in Combination With Radiation Therapy for the Treatment of Very High Risk Prostate Cancer, OPTIMAL Trial

Optimizing Treatment and Advanced Multi-Imaging Response Evaluation for Very-High-Risk Prostate Cancer (OPTIMAL) - a Phase II Single Arm Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Northwestern University · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well relugolix and enzalutamide, in combination with radiation therapy, works in treating patients with very high risk prostate cancer. Relugolix is a form of androgen deprivation therapy. It prevents the release of testosterone, a hormone required to sustain prostate growth. Reducing testosterone levels may inhibit the proliferation of prostate tumor cells that need testosterone to grow. Enzalutamide is an androgen receptor signaling inhibitor. It inhibits the activity of prostate tumor cell receptors, which may reduce proliferation of prostate tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Adding relugolix and enzalutamide to radiation therapy may be more effective at treating patients with very high risk prostate cancer than giving any of these treatments alone.

Detailed description

PRIMARY OBJECTIVE: I. To determine the efficacy of radiation therapy (RT) with androgen deprivation therapy (ADT) (relugolix) and an androgen receptor signaling inhibitor (enzalutamide), for a total duration of 18 months, in patients with National Comprehensive Cancer Network (NCCN) very high-risk prostate cancer, as determined by a 2-year biopsy positivity rate. SECONDARY OBJECTIVES: I. To determine the 4-year disease free survival (DFS) (biochemical failure of prostate specific antigen \[PSA\] nadir +2ng/mL, local or regional recurrence, distant metastasis, or death from any cause). II. To evaluate testosterone recovery. EXPLORATORY OBJECTIVES: I. To evaluate impact on patient-reported health-related quality of life utilizing (1) Expanded Prostate Cancer Index Composite, EPIC-26 and (2) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLC-C30). II. To investigate a relationship between magnetic resonance imaging (MRI)-positron emission tomography (PET) radiomic response (baseline and after neoadjuvant therapy) correlated with pathologic and disease control endpoints. OUTLINE: Patients receive relugolix orally (PO) once daily (QD) and enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 18 months in the absence of disease progression or unacceptable toxicity. After 4 months of treatment with relugolix and enzalutamide, patients begin image-guided radiation therapy (IGRT) per standard of care. Patients also undergo fluorine F 18 piflufolastat PET/MRI and CT on the trial, undergo collection of blood samples throughout the trial, and undergo biopsy during follow up. After completion of study treatment, patients are followed up every 3-6 months for up to 30 months (48 months after study registration).

Conditions

• Prostate Adenocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Enzalutamide	Given PO
OTHER	Fluorine F 18 Piflufolastat	Undergo fluorine F 18 piflufolastat PET/MRI
RADIATION	Image Guided Radiation Therapy	Undergo IGRT
PROCEDURE	Magnetic Resonance Imaging	Undergo PET/MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/MRI
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Relugolix	Given PO

Timeline

• Start date: 2024-09-06
• Primary completion: 2028-11-19
• Completion: 2032-11-19
• First posted: 2024-07-15
• Last updated: 2025-10-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study