Relugolix + Radiation for Advanced-Stage Prostate Cancer

(NRG PROMETHEAN Trial)

Recruiting at 257 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: NRG Oncology

Must be taking: GnRH antagonists

Must not be taking: Androgen deprivation

Disqualifiers: Local tumor recurrence, Spinal cord compression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

194 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug relugolix (also known as Orgovyx, Relumina, or Myfembree) to standard radiation therapy better controls prostate cancer that has spread to a few other areas. Relugolix lowers testosterone levels, potentially stopping cancer growth. Participants will receive either relugolix with radiation or a placebo with radiation. The trial seeks men with prostate cancer that has spread to limited areas and who are not currently on hormone therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently on androgen deprivation or anti-androgen therapy, you would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that relugolix is generally safe for patients with advanced prostate cancer. It quickly lowers testosterone levels, helping to control the cancer. Most patients do not experience serious side effects, though some may feel tired or have hot flashes.

Stereotactic Body Radiation Therapy (SBRT) is also a proven safe treatment. Studies indicate its effectiveness, and most patients tolerate it well. Side effects are usually mild and may include fatigue or changes in bowel habits.

Both treatments have a strong safety record, offering reassurance to those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about relugolix combined with stereotactic body radiation therapy (SABR) for advanced-stage prostate cancer because relugolix offers a new approach to hormone therapy. Unlike traditional treatments like leuprolide, which require injections and can take time to significantly reduce testosterone levels, relugolix is an oral medication that rapidly lowers testosterone by directly blocking receptors in the pituitary gland. This potentially means fewer side effects and a quicker response compared to existing therapies. Additionally, when paired with the precision targeting of SABR, this combination could enhance cancer control while minimizing damage to surrounding healthy tissues.

What evidence suggests that relugolix plus radiation therapy could be an effective treatment for advanced-stage prostate cancer?

Studies have shown that relugolix, a daily pill, effectively treats advanced prostate cancer by quickly lowering testosterone levels, which the cancer needs to grow. Over 90% of patients maintained low testosterone levels, crucial for slowing cancer progression. Additionally, real-world data shows that more than 98% of patients reached these desired testosterone levels with relugolix. In this trial, some participants will receive relugolix alongside stereotactic body radiation therapy (SBRT).

SBRT is another effective treatment, using precise, high-dose radiation to target and kill prostate cancer cells. Research supports its success and safety for treating both localized and spread prostate cancer. This trial will compare the combination of relugolix with SBRT to a placebo with SBRT, potentially improving treatment by both lowering testosterone and directly attacking cancer cells. ^{1 3 5 6 7}

Who Is on the Research Team?

Bridget F Koontz

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Men aged 18+ with advanced-stage prostate cancer that has spread to a limited number of other body parts (1-5 sites). They must have had prior treatment for prostate cancer, no severe comorbidities preventing protocol completion, and agree to use effective contraception. Excluded are those with only intrapelvic lymph node recurrence or certain heart conditions.

Inclusion Criteria

My hepatitis C is cured or undetectable while on treatment.

I've been mostly active and able to care for myself in the last 4 months.

My hepatitis B virus load is undetectable with current treatment.

Exclusion Criteria

My prostate cancer has come back only in the lymph nodes in my pelvis.

I have had radiation therapy on a cancerous lesion.

I have inflammatory bowel disease and am planned for radiotherapy in the abdomen or pelvis area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or relugolix orally once daily for 180 days and undergo stereotactic ablative body radiation therapy (SABR) for 1-3 weeks

26 weeks

Regular visits for radiation therapy and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 9 and 12 months, every 6 months up to month 60, and annually thereafter

Up to 5 years

Follow-up visits at specified intervals

What Are the Treatments Tested in This Trial?

Interventions

• Relugolix
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing if adding Relugolix to usual radiation therapy can shrink tumors in men with oligometastatic prostate cancer. Relugolix lowers testosterone which may inhibit tumor growth. Participants will either receive Relugolix or a placebo alongside their radiation treatments.

How Is the Trial Designed?

Group I: Arm II (relugolix, SABR) Experimental Treatment 9 Interventions

Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.

Group II: Arm I (placebo, SABR) Placebo Group 9 Interventions

Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.

Relugolix is already approved in United States, Japan, European Union for the following indications:

Approved in United States as Orgovyx for:

• Advanced prostate cancer
• Uterine fibroids

Approved in Japan as Relumina for:

• Uterine fibroids

Approved in European Union as Orgovyx for:

• Advanced prostate cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

In a study of 258 patients with localized prostate cancer treated with SABR (Stereotactic Ablative Body Radiotherapy), significant dosimetric predictors for late toxicity and quality of life (QOL) were identified, particularly focusing on high-dose regions in the bladder and rectum.

The analysis revealed that avoiding high doses in the bladder and rectum is crucial, as bladder V38 was a significant predictor of QOL, while rectal Dmax, V38, and bladder D2cc were key predictors of late toxicity, emphasizing the importance of careful dose planning in SABR treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy. Alayed, Y., Davidson, M., Quon, H., et al.[2021]

In the phase III HERO trial, relugolix demonstrated a sustained castration rate of over 90% in men with advanced prostate cancer over 48 weeks, which was non-inferior to the traditional treatment with leuprolide, and showed potential superiority in exploratory analyses.

Relugolix is generally well tolerated and may have a lower risk of major adverse cardiac events compared to leuprolide, making it a promising oral treatment option for rapid testosterone suppression without the initial surge associated with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. Shirley, M.[2023]

In a phase 2 study involving 103 intermediate-risk prostate cancer patients, relugolix achieved effective castration rates of 95% and 82% for testosterone levels below 1.73 nmol/l and 0.7 nmol/l, respectively, within just 4 days of treatment.

Relugolix demonstrated a favorable safety profile similar to that of degarelix, with common side effects like hot flushes, and showed potential as an effective oral alternative to injectable androgen deprivation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Oral Gonadotropin-releasing Hormone Receptor Antagonist Relugolix as Neoadjuvant/Adjuvant Androgen Deprivation Therapy to External Beam Radiotherapy in Patients with Localised Intermediate-risk Prostate Cancer: A Randomised, Open-label, Parallel-group Phase 2 Trial. Dearnaley, DP., Saltzstein, DR., Sylvester, JE., et al.[2023]

In a study of 70 patients with nonmetastatic prostate cancer treated with stereotactic body radiation therapy (SBRT), CyberKnife showed significantly lower peak acute genitourinary (GU) toxicity compared to volumetric-modulated arc therapy (VMAT), with IPSS scores of 16.2 versus 20.2, respectively.

The incidence of grade 2 acute GU toxicity was lower in the CyberKnife group (22.9%) compared to the VMAT group (45.7%), suggesting that CyberKnife may be a safer option for minimizing acute prostate symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for prostate cancer: a study comparing 3-year genitourinary toxicity between CyberKnife and volumetric-modulated arc therapy by propensity score analysis. Ito, M., Yoshioka, Y., Takase, Y., et al.[2023]

In a study of 91 patients prescribed relugolix for prostate cancer, 78% filled their prescriptions, and 93% reported never missing a dose, indicating good compliance with the oral medication.

No major safety concerns were identified, even when relugolix was used in combination with other therapies, and most patients who switched from other androgen deprivation therapies reported similar or improved tolerance with relugolix.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Practical Guide to Relugolix: Early Experience With Oral Androgen Deprivation Therapy. Kasparian, S., Wei, O., Tsai, NC., et al.[2023]

In a study of 84 low-risk prostate cancer patients treated with Stereotactic Ablative Body Radiotherapy (SABR), long-term quality of life (QOL) outcomes were generally positive, with a median follow-up of 50.8 months, although some patients reported declines in urinary (17.9%), bowel (26.2%), and sexual (37.5%) QOL domains.

Dosimetric factors such as rectal D1cc and penile bulb V35 were identified as significant predictors of worse QOL, highlighting the importance of adhering to strict dosimetric constraints to minimize side effects from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. Elias, E., Helou, J., Zhang, L., et al.[2018]

In a study of 52 men with intermediate to high-risk prostate cancer, the oral GnRH receptor antagonist relugolix, when combined with stereotactic body radiotherapy (SBRT), achieved a profound testosterone suppression rate of 92.3%, demonstrating its efficacy in managing hormone levels before treatment.

By 4 months post-SBRT, 87.2% of patients had PSA levels ≤ 0.5 ng/mL, indicating a strong early response to treatment, suggesting that relugolix can be a preferred option for patients who may have concerns about injectable therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early biochemical outcomes following neoadjuvant/adjuvant relugolix with stereotactic body radiation therapy for intermediate to high risk prostate cancer. Gallagher, L., Xiao, J., Hsueh, J., et al.[2023]

In a phase 3 study involving 934 men with advanced prostate cancer, relugolix, an oral medication, showed similar health-related quality of life (HRQOL) outcomes compared to leuprolide, an injectable treatment, during the treatment phase.

During the testosterone recovery phase, patients on relugolix reported fewer hormone-related symptoms than those on leuprolide, indicating that relugolix may offer a more favorable side effect profile and quicker testosterone recovery after treatment cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Relugolix Versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Tombal, B., Collins, S., Morgans, AK., et al.[2023]

In a study involving 32 patients with early-stage prostate cancer treated with Cyberknife, 29 patients remained free of disease at the last follow-up, indicating strong efficacy of this treatment.

While some patients experienced mild to moderate side effects, including acute genitourinary toxicity and proctitis, all patients were alive at the last follow-up, suggesting that Cyberknife is a safe option for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyberknife treatment for low and intermediate risk prostate cancer. Detti, B., Bonomo, P., Masi, L., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10198864/

Relugolix: A Review in Advanced Prostate Cancer - PMC In a key clinical trial in men with advanced prostate cancer, once-daily relugolix provided sustained castration in > 90% of patients, with a ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004325

Oral Relugolix for Androgen-Deprivation Therapy in ... In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2815669

Efficacy and Safety of Radiotherapy Plus Relugolix in Men ... The results of these 2 randomized clinical trials suggest that relugolix rapidly achieves sustained castration in patients with localized and advanced prostate ...

4. onclive.com onclive.com/view/optyx-study-offers-preliminary-glance-into-real-world-use-of-relugolix-in-advanced-prostate-cancer

OPTYX Study Offers Preliminary Glance Into Real-World ... Data from OPTYX showed that most patients (52.2%) in the overall population (n = 999) received relugolix in combination with other prostate ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2950393025000816

Relugolix in prostate cancer therapy: Clinical evidence and ... Real-world studies performed to date have confirmed the effectiveness of relugolix, with more than 98% patients achieving castrate testosterone levels.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03085095

A Study to Evaluate the Safety and Efficacy of Relugolix ... The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum ...

7. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.156

Safety and tolerability of relugolix in combination with ... Safety and tolerability of relugolix in combination with abiraterone or apalutamide for treatment of advanced prostate cancer: Data from a 52- ...