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

NCT06499870 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 24U02NCI-2024-03934STU00221219P30CA060553
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic response (biopsy positivity rate)

  Will determine the efficacy of radiation therapy with relugolix and enzalutamide, for a total duration of 18 months, in patients with National Comprehensive Cancer Network very high-risk prostate cancer, by a 2-year biopsy positivity rate.

  At 2 years

Secondary Outcomes (2)

• Disease-free survival

  Up to 4 years

• Testosterone recovery

  Up to 4 years

Study Arms (1)

Treatment (relugolix, enzalutamide, IGRT)

EXPERIMENTAL

Patients receive relugolix PO 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 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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Enzalutamide; Other: Fluorine F 18 Piflufolastat; Radiation: Image Guided Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Questionnaire Administration; Drug: Relugolix

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (relugolix, enzalutamide, IGRT)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (relugolix, enzalutamide, IGRT)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (relugolix, enzalutamide, IGRT)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV 3100, MDV-3100, MDV3100, Xtandi

Treatment (relugolix, enzalutamide, IGRT)

Fluorine F 18 Piflufolastat OTHER

Undergo fluorine F 18 piflufolastat PET/MRI

Also known as: 18F-DCFPyL, Fluorine F 18 DCFPyL, Piflufolastat F 18, Piflufolastat F-18, Piflufolastat F18, Pylarify

Treatment (relugolix, enzalutamide, IGRT)

Image Guided Radiation Therapy RADIATION

Undergo IGRT

Also known as: IGRT, image-guided radiation therapy, Image-Guided Radiotherapy

Treatment (relugolix, enzalutamide, IGRT)

Magnetic Resonance Imaging PROCEDURE

Undergo PET/MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (relugolix, enzalutamide, IGRT)

Positron Emission Tomography PROCEDURE

Undergo PET/MRI

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (relugolix, enzalutamide, IGRT)

Questionnaire Administration OTHER

Ancillary studies

Treatment (relugolix, enzalutamide, IGRT)

Relugolix DRUG

Given PO

Also known as: N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385, TAK-385, TAK385

Treatment (relugolix, enzalutamide, IGRT)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed prostate adenocarcinoma consistent with NCCN very-high-risk (VHR) prostate cancer defined with at least one of the following:
• cT3b-cT4 (American Joint Committee on Cancer \[AJCC\] 9.0)
• \> 4 cores with grade group 4 or 5 prostate cancer
• Primary gleason pattern 5
• or 3 NCCN high-risk features.
• Patients with involved pelvic lymph nodes below the common iliac bifurcation will be allowed as long as the criteria for VHR (very-high risk) are met
• Patients must be age ≥ 18 years
• Patients must have testosterone \> 50 ng/dL within 90 days prior to registration
• Note: Prior androgen deprivation (gonadotrophin releasing hormone \[GnRH\] analog and/or non-steroidal antiandrogen) therapy is allowed provided that it is less than 60 days of prior total duration and that serum testosterone concentration must be ≥ 50 ng/dL prior to enrollment; 5-alpha reductase inhibitors will not impact eligibility, but must be discontinued prior to starting protocol treatment
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Leukocytes (white blood cells \[WBC\]) ≥ 2,500/mcL
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Hemoglobin (Hgb) ≥ 8 g/dL
• Platelets (PLT) ≥ 80,000/mcL
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 3 x institutional upper limit of normal (ULN)

You may not qualify if:

• Patients with definitive clinical or radiologic evidence of metastatic disease
• Patients with prior invasive malignancy (except non-melanomatous skin cancer carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years
• Prior radiotherapy that would result in overlap of radiation therapy fields
• Patients who have a history of any of the following:
• History of documented inflammatory bowel disease
• Symptomatic congestive heart failure (New York Heart Association Functional Classification III/IV) within 4 months prior to registration
• Unstable angina pectoris requiring hospitalization within the last 4 months prior to registration
• History of seizure disorder or condition that may yield a high risk of seizure (e.g., prior cortical stroke or significant brain trauma)
• Psychiatric illness/social situations that would limit compliance with study requirements
• History of repeated falls and fractures over the past 12 months that in the opinion of the treating investigator would put the patient at risk for poor bone outcomes from androgen receptor targeted therapy
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Patients with the inability to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of enzalutamide and relugolix

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Interventions

Biopsy; Specimen Handling; enzalutamide; 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid; Radiotherapy, Image-Guided; Magnetic Resonance Spectroscopy; relugolix

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Radiotherapy; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sean Sachdev

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 15, 2024
• Study Start: September 6, 2024
• Primary Completion (Estimated): November 19, 2028
• Study Completion (Estimated): November 19, 2032
• Last Updated: October 21, 2025

Record last verified: 2025-10

Locations

US (1)