Relugolix + Radiation Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must be taking: Androgen deprivation

Must not be taking: Anti-neoplastic agents

Disqualifiers: Psychiatric illness, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 12-24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the optimal duration for administering relugolix alongside radiation therapy to treat high-risk prostate cancer. Prostate cancer often grows with the help of testosterone, and relugolix, a medication that lowers testosterone levels, may slow the cancer's growth. Participants will receive radiation therapy and relugolix for either 12 or 24 months to determine which duration is more effective. Men diagnosed with high-risk prostate cancer, such as those with a PSA level over 20 or specific tumor characteristics, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in prostate cancer treatment.

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

The trial does not specify if you need to stop taking your current medications, but you cannot use other cancer treatments while participating. If you're on androgen deprivation therapy, your testosterone levels must be above 50 ng/dL, and bicalutamide at 50 mg/daily or less is allowed.

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 prostate cancer. Common side effects include hot flashes, fatigue, weakness, constipation, and muscle pain. Importantly, no new safety concerns emerged when relugolix was combined with radiation therapy.

Studies on radiation therapy indicate it is safe for treating prostate cancer. Safety checks reveal that patients usually do not experience severe side effects. Additionally, highly targeted radiation methods have demonstrated excellent safety, with no serious adverse events reported.

Overall, both relugolix and radiation therapy maintain strong safety records for treating prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Unlike the standard treatment options for prostate cancer, which often involve surgical removal and older hormone therapies like leuprolide, the combination of Relugolix with radiation therapies offers a new way to manage the condition. Relugolix is a novel oral medication that targets and suppresses testosterone production more rapidly and effectively than traditional injectable hormone therapies. This can potentially lead to fewer side effects and improved patient comfort since it's taken as a daily pill rather than an injection. Additionally, the integration of advanced imaging techniques like PSMA PET scans allows for more precise treatment planning and monitoring, which could enhance the effectiveness of the radiation therapy. Researchers are excited about these features because they could lead to improved outcomes and a better quality of life for patients.

What evidence suggests that relugolix combined with radiation therapy could be an effective treatment for prostate cancer?

Research shows that relugolix can lower testosterone levels, potentially slowing prostate cancer growth. In studies, over 90% of patients achieved the desired drop in testosterone. This is significant because testosterone often fuels prostate cancer growth. In this trial, participants will receive relugolix alongside radiation therapy, which may enhance treatment effectiveness. Radiation therapy alone controls prostate cancer by precisely targeting cancer cells. Combining relugolix with radiation therapy might provide a better treatment option for those with high-risk prostate cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Xinglei Shen

Principal Investigator

University of Kansas

Are You a Good Fit for This Trial?

This trial is for men over 18 with high risk prostate cancer who can consent to the study, have a life expectancy over 5 years, and are eligible for radiation therapy combined with ADT. They must have good organ function and agree to use contraception. It's not for those in other clinical trials, using anti-cancer drugs, with severe infections or psychiatric/social limitations, allergic reactions to study drug components, current ADT (unless testosterone levels are adequate), or prior treatments that overlap with this study.

Inclusion Criteria

Hemoglobin ≥ 9 g/dL

Life expectancy > 5 years

Platelets >= 100 K/UL

Exclusion Criteria

Simultaneously enrolled in any therapeutic clinical trial

I am not using, nor plan to use, other cancer treatments during this study.

I have had surgery to remove my prostate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive relugolix orally once daily. Cycles repeat every 3 months for 12 or 24 months, with brachytherapy and external beam radiation over 25 fractions starting 30 to 180 days after relugolix initiation.

12-24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment. Arm A: every 3 months for 12 months, then every 6 months up to 36 months. Arm B: every 6 months up to 36 months.

Up to 36 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Relugolix

Trial Overview The trial is testing how long relugolix should be given alongside standard radiation therapy in treating high-risk prostate cancer. Relugolix lowers testosterone which may help slow down the growth of prostate cancer cells. The goal is to find out if adding relugolix improves outcomes and has fewer side effects than previous hormonal therapies.

How Is the Trial Designed?

Group I: Arm B (relugolix, brachytherapy, external beam radiation) Experimental Treatment 10 Interventions

Patients receive relugolix PO QD. Cycles repeat every 3 months for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.

Group II: Arm A (relugolix, brachytherapy, external beam radiation) Experimental Treatment 10 Interventions

Patients receive relugolix PO QD. Cycles repeat every 3 months for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II study involving 40 high-risk prostate cancer patients, dose-escalated hypofractionated radiotherapy (hfrt) combined with androgen suppression therapy was found to be feasible, delivering 75 Gy in 25 fractions with minimal acute gastrointestinal and genitourinary toxicities.

Only 16.6% of patients experienced grade 2 genitourinary toxicity and 12.9% experienced gastrointestinal toxicity, indicating that the treatment can be administered safely while still targeting the pelvic lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer. Drodge, CS., Boychak, O., Patel, S., et al.[2018]

Transrectal ultrasound-guided prostate brachytherapy is the most advanced method for delivering radiation, achieving lower prostate-specific antigen (PSA) levels than other treatments like IMRT, while maintaining biochemical control in about 90% of patients.

Brachytherapy as an organ-conserving treatment results in lower rates of erectile dysfunction and urinary incontinence compared to surgery, making it a safer option for patients with low-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity. Kao, J., Cesaretti, JA., Stone, NN., et al.[2022]

Prostate cancer cells exhibit high levels of autophagy, indicated by high LC3A and low LAMP2a levels, which are associated with poorer outcomes in patients treated with radical radiotherapy.

Blocking components of the autophagy pathway can increase the sensitivity of prostate cancer cells to radiation, suggesting that targeting autophagy may enhance the effectiveness of radiotherapy in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensified autophagy compromises the efficacy of radiotherapy against prostate cancer. Koukourakis, MI., Kalamida, D., Mitrakas, A., et al.[2022]

Intensity Modulated Radiotherapy (IMRT) allows for more precise targeting of tumors while sparing surrounding healthy tissues, making it the current standard for treating head and prostate cancers.

The integration of image-guided radiotherapy (IGRT) is crucial for addressing challenges like tumor motion and anatomical changes during treatment, ensuring better delivery of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in radiotherapy. Bhide, SA., Nutting, CM.[2022]

Prostate cancer patients receiving image-guided radiotherapy (IGRT) experienced significantly less severe acute toxicity, such as urinary frequency, diarrhoea, and fatigue, compared to those who did not receive IGRT, with 23% vs 7% for urinary frequency ≥G3 and 15% vs 3% for diarrhoea ≥G2.

The onset of these toxicities was earlier in the non-IGRT group, indicating that IGRT not only reduces the severity of symptoms but also delays their onset, leading to a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Gill, S., Thomas, J., Fox, C., et al.[2021]

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9399820/

Long-term outcomes of prostate intensity-modulated ... Multiple randomized trials have shown that dose-escalated RT leads to improved biochemical control of prostate cancer ( Table 3 ) (1–3, 6–8). ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2287888223000041

The oncologic and safety outcomes of low-dose-rate ... Combination therapy was shown to be non-superior to LDR brachytherapy alone (5-year progression-free survival, LDR brachytherapy alone: 86% vs. LDR ...

3. academic.oup.com academic.oup.com/jrr/article/66/1/39/7954234

Real-world comparative outcomes and toxicities after ... This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A ...

4. tau.amegroups.org tau.amegroups.org/article/view/17922/html

Intensity-modulated radiotherapy for prostate cancer Multiple clinical trials have demonstrated improved cancer outcomes with dose escalation, but toxicities using 3D-CRT and escalated doses have been problematic.

5. urotoday.com urotoday.com/conference-highlights/astro-2024/astro-2024-prostate-cancer/155302-astro-2024-a-randomized-comparison-of-low-dose-rate-or-high-dose-rate-brachytherapy-combined-with-external-beam-radiation-for-unfavorable-intermediate-or-high-risk-prostate-cancer-efficacy-results-at-median-6-years.html

ASTRO 2024: A Randomized Comparison of Low Dose ... A randomized trial comparing low- and high-dose rate brachytherapy, combined with external beam radiotherapy, for intermediate- or high-risk prostate cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10513906/

The oncologic and safety outcomes of low-dose-rate ... Table 2 shows a comparison of oncologic outcomes between LDR brachytherapy and intensity-modulated radiation therapy (IMRT) in low- and intermediate-risk ...

7. uclahealth.org uclahealth.org/news/release/study-confirms-safety-and-efficacy-higher-dose-per-day

Study confirms safety and efficacy of higher-dose-per-day ... The analysis found patients who received isodose MHFRT (60 Gy in 20 fractions) had similar cancer control and side effects compared to those ...

8. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/shorter-radiation-improves-patient-experience-but-not-disease-control-for-intermediate-risk-prostate

Shorter radiation improves patient experience but not ... Patients treated with stereotactic body radiation therapy (SBRT) reported fewer declines in bowel, urinary and sexual functioning but were more ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1879850023001753

Long-Term Outcomes of a Prospective Study on Highly ... No grade ≥3 adverse events were observed, suggesting that highly hypofractionated IMRT is a safe treatment. Conventional fractionated radiation therapy at 1.8 ...