The SUGAR Study: (SBRT and Ultrashort GnRH Antagonist-Relugolix) for Clinicogenomic Unfavorable Intermediate Risk Prostate Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to measure the toxicity and effectiveness of the following treatments for cFIR/cgUIR prostate cancer patients. Stereotactic body radiotherapy (SBRT) alone or Stereotactic body radiotherapy (SBRT) combined with Ultrashort GNRH Antagonist called Relugolix (an oral drug). Treatments will be randomly assigned to study patients. The main questions it aims to answer are the following: Whether the proportion of men who undergo SUGAR have a superior rate of attaining PSA nadir of <= 0.2 compared to SBRT alone, and Whether SUGAR is superior to historical rates of minimal clinically important decline (MCID) in sexual and hormonal function at 6 months for patients undergoing 6 months of androgen deprivation therapy (ADT) Men aged 18+ with cFIR/cgUIR will be enrolled. Specifically, patients must meet one of the following 2 criteria: 1) Gleason score must be Gleason 3+4 with a PSA < 20 ng/mL, or 2) Gleason 6 (3+3) and PSA > 10 ng/mL and < 20 ng mL.

Detailed Description
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Unfavorable Intermediate Risk (UIR) Prostate Cancer is prostate cancer that is localized and curable but may require more treatment than external beam radiotherapy (EBRT) alone. In contrast, favorable intermediate risk (FIR) prostate cancer can be treated by EBRT alone. There is evidence that some prostate cancer that is classified through clinical factors as FIR can act more aggressively if also associated with a high risk gene expression score. This type of prostate cancer (traditionally favorable intermediate risk, but with a gene signature that predicts for aggressive disease) presents a treatment dilemma. Recent evidence suggests that androgen deprivation therapy (ADT) is generally beneficial for intermediate risk prostate cancer and so it is possible that these patients (with favorable intermediate risk based on non-genetic factors but with high genetic risk) may also benefit. However, ADT causes very bothersome side effects including hot flashes, fatigue, sexual disfunction, and in some cases, heart problems. In order to balance the benefit and harms of ADT in combination with radiation, we could reduce the length of ADT and make it precisely overlap with radiation treatment. The oral ADT medication Relugolix (Orgovyx) is ideal for this purpose. In addition to shortening ADT, it is important to measure any potential benefit when ADT is added to stereotactic body radiotherapy (SBRT). SBRT is a shorter and more intense version of standard fractionation EBRT. Therefore, a multicenter randomized phase III study comparing prostate cancer control and quality of life with SBRT + Ultrashort GNRH Antagonist Relugolix (SUGAR) vs. SBRT alone for a category of clinicogenomic unfavorable intermediate risk patients with favorable clinical features and high risk genetic features.

Official Title
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The SUGAR Study: (SBRT and Ultrashort GnRH Antagonist-Relugolix) for Clinicogenomic Unfavorable Intermediate Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Relugolix 120 MG [Orgovyx]
* Radiation: SBRT standard of care radiotherapy treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Exclusion Criteria: Current use of medications that cause QT prolongation Known allergic reactions to relugolix Treatment with another investigational drug or other intervention within 30 days of enrollment Ulcerative colitis or other inflammatory bowel disease history Connective tissue disease such as lupus, scleroderma, or dermatomyositis GNRH antagonist therapy or SBRT to the prostate are medically contraindicated or not tolerated History of long QT syndrome documented in the medical record The following ECG abnormalities are excluded: Q-wave infarction unless identified 6 or more months before the Screening Visit QT interval corrected for heart rate (QTc) > 470 msec. If the QTc is prolonged in a patient with a pacemaker, the patient may be enrolled in the study upon discussion with the study PI Congenital long QT syndrome Q History of surgical castration Prior treatment for prostate cancer with surgery or prostate directed radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will undergo baseline tests at the beginning of the study and will be randomized to receive Stereotactic body radiotherapy (SBRT) + Ultrashort GNRH Antagonist Relugolix (SUGAR) vs. Stereotactic body radiotherapy (SBRT) alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stereotactic body radiotherapy<br>SBRT Though a range of doses are delivered nationally for IR prostate cancer, the most common regimen is 7.25 Gy- 8.00 Gy x 5 fractions, given over 2 weeks. | Radiation: SBRT standard of care radiotherapy treatment<br>* SBRT is a standard-of-care radiotherapy treatment for intermediate-risk prostate cancer.<br>|
| Active Comparator: Relugolix and SBRT<br>SBRT and Relugolix SBRT along with 30 days of total relugolix (study drug) will be used. Relugolix starting 14 days to 17 days prior to the first treatment. | Drug: Relugolix 120 MG [Orgovyx]<br>* ORGOVYX will be initiated with a loading dose of 360 mg on the first day and continue treatment with a 120 mg dose taken orally once daily at approximately the same time each day. Total length of treatment will be 30 days.<br>* Other names: SBRT standard of care radiotherapy treatment and Relugolix;Radiation: SBRT standard of care radiotherapy treatment<br>* SBRT is a standard-of-care radiotherapy treatment for intermediate-risk prostate cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants that attain PSA nadir | The proportion of men who undergo SUGAR that attain PSA nadir of <= 0.2ng/mL compared to SBRT alone. | up to 2 years post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of life assessment using the EPIC-26 survey | The EPIC-26 is a validated instrument that measures health-related quality of life over 5 domains: Urinary incontinence, Urinary irritative/obstructive, Bowel, Sexual, Hormonal. Range of scores are 0-100. Higher scores indicate higher quality of life. | up to 2 years post treatment |