Recruiting

Phase 2

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

Sponsor:

Sean Sachdev

Code:

NCT06499870

Conditions

Prostate Adenocarcinoma

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy

Biospecimen Collection

Computed Tomography

Enzalutamide

Fluorine F 18 Piflufolastat

Study Details

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

Study ID

NCT06499870

Start date

Sep 6, 2024

Status verified date

May, 2026

Completion date

Nov 19, 2032

Anticipated

Primary completion date

Nov 19, 2030

Anticipated

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
2 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)
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN
Creatinine ≤ institutional ULN
Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m\^2

Estimated GFR (eGFR) is estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation
For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 3 months prior to registration with a CD4 count of ≥ 200 cells/μL. Note also that HIV testing is not required for eligibility for this protocol as it is self-reported
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be better than class III
Patients must not have contraindications to magnetic resonance (MR) imaging and be able to lie flat and still for approximately 30-40 minutes and be able to tolerate PET/CT imaging and radiation therapy treatment planning and delivery
Patients with female partners of reproductive potential must agree to use effective contraception during treatment with and for 3 months after the last dose. Male patients must use a condom during sex with a pregnant woman
Patients must have the ability to understand and the willingness to sign a written informed consent document and comply with the study requirements

Exclusion Criteria:

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

Study Design

Enrollment

50 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (relugolix, enzalutamide, IGRT)

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.

Interventions

Biopsy

Undergo biopsy

Biospecimen Collection

Undergo collection of blood samples

Computed Tomography

Undergo CT

Enzalutamide

Given PO

Fluorine F 18 Piflufolastat

Undergo fluorine F 18 piflufolastat PET/MRI

Image Guided Radiation Therapy

Undergo IGRT

Magnetic Resonance Imaging

Undergo PET/MRI

Positron Emission Tomography

Undergo PET/MRI

Questionnaire Administration

Ancillary studies

Relugolix

Given PO

Primary outcome measure

Pathologic response (biopsy positivity rate) [ Time Frame: At 2 years ]

Central Contacts and Locations

Locations

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Study Coordinator

(312) 695-0990 cancer@northwestern.edu

Principal Investigator:

Sean Sachdev, MD

More Information

Sponsor

Sean Sachdev

Last update posted

Jun 5, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Sean Sachdev on 2026-06-05.