AzTrials
AzTrials

Prostate AdenocarcinomaPhase 2NCT06499870

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

A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Prostate Adenocarcinoma, run by Sean Sachdev at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Adenocarcinoma
What is being tested?
Biopsy, Biospecimen Collection and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
6 Sep 2024to 19 Nov 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • Northwestern University

    Chicago, Illinois, 60611

    Study Coordinator, (312) 695-0990, cancer@northwestern.edu

    Sean Sachdev, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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).

Being tested
Biopsy, Biospecimen Collection, Computed Tomography, Enzalutamide, Fluorine F 18 Piflufolastat

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • EnzalutamideDrug

    Also called ASP9785, MDV 3100, MDV-3100, MDV3100

    Given PO

  • Fluorine F 18 PiflufolastatOther

    Also called 18F-DCFPyL, Fluorine F 18 DCFPyL, Piflufolastat F 18, Piflufolastat F-18

    Undergo fluorine F 18 piflufolastat PET/MRI

  • Image Guided Radiation TherapyRadiation

    Also called IGRT, image-guided radiation therapy, Image-Guided Radiotherapy

    Undergo IGRT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo PET/MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/MRI

  • Questionnaire AdministrationOther

    Ancillary studies

  • RelugolixDrug

    Also called 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

    Given PO

Study groups in NCT06499870
Study groupRoleWhat they receive
Treatment (relugolix, enzalutamide, IGRT)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 2 years

Secondary outcomes (2)

  1. Disease-free survival

    Will be determined by biochemical failure of prostate specific antigen nadir + 2ng/mL, local or regional recurrence, distant metastasis, or death. Median survival time will be estimated with corresponding 95% confidence intervals.

    Measured: Up to 4 years

  2. Testosterone recovery

    Testosterone recovery will be defined as a total serum testosterone of ≥ 200 ng/dL.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2024
  2. Study start6 Sep 2024
  3. Primary completion19 Nov 2030 (estimated)
  4. Study completion19 Nov 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06499870
Sponsor's protocol ID
NU 24U02
Other IDs
NCI-2024-03934, STU00221219, NU 24U02, P30CA060553
Status last verified
May 2026
First submitted
8 Jul 2024
Last updated
5 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Prostate Adenocarcinoma, run by Sean Sachdev at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic response (biopsy positivity rate) (time frame: At 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06499870.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in