Relugolix + Radiation for Advanced-Stage Prostate Cancer

(NRG PROMETHEAN Trial)

Recruiting at 228 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This phase II trial compares the usual treatment of radiation therapy alone to using the study drug, relugolix, plus the usual radiation therapy in patients with castration-sensitive prostate cancer that has spread to limited other parts of the body (oligometastatic). Relugolix is in a class of medications called gonadotropin-releasing hormone (GnRH) receptor antagonists. It works by decreasing the amount of testosterone (a male hormone) produced by the body. It may stop the growth of cancer cells that need testosterone to grow. Radiation therapy uses high-energy x rays or protons to kill tumor cells. The addition of relugolix to the radiation may reduce the chance of oligometastatic prostate cancer spreading further.

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.

What data supports the effectiveness of the drug Relugolix for advanced-stage prostate cancer?

Research shows that Relugolix, an oral drug, effectively lowers testosterone levels in men with advanced prostate cancer, similar to other treatments but with potentially better heart safety. It also works well when combined with radiation therapy, offering a shorter treatment time with similar effectiveness. ^{1 2 3 4 5}

Is the combination of Relugolix and radiation therapy safe for treating prostate cancer?

Studies on stereotactic ablative radiotherapy (SABR) using the CyberKnife system for prostate cancer show it is generally safe, with some patients experiencing mild to moderate side effects like genitourinary toxicity (issues with the urinary system) and proctitis (inflammation of the rectum). These studies suggest that the treatment is effective and safe for localized prostate cancer. ^{6 7 8 9 10}

How is the treatment Relugolix + Radiation unique for advanced-stage prostate cancer?

Relugolix is an oral medication that quickly lowers testosterone levels without the initial surge seen with other treatments, and it may have fewer heart-related side effects. When combined with Stereotactic Body Radiation Therapy (SBRT), it offers a potentially more convenient and effective treatment option for advanced-stage prostate cancer compared to traditional methods. ^{1 2 3 4 5}

Research Team

Bridget F Koontz

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Relugolix (Hormone Therapy)
• Stereotactic Body Radiation Therapy (Radiation)

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.

Participant Groups

Group I: Arm II (relugolix, SABR) Experimental Treatment 10 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 10 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 Japan for the following indications:

Approved in Japan as Relumina for:

• Uterine fibroids

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+

Findings from Research

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 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 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 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]

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 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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A Practical Guide to Relugolix: Early Experience With Oral Androgen Deprivation Therapy. [2023]

2. Switzerland 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. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Early biochemical outcomes following neoadjuvant/adjuvant relugolix with stereotactic body radiation therapy for intermediate to high risk prostate cancer. [2023]

4. France pubmed.ncbi.nlm.nih.gov

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

5. Switzerland 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. [2017]

7. England 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. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Cyberknife treatment for low and intermediate risk prostate cancer. [2015]

10. Ireland pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. [2018]