SBRT + Relugolix for Prostate Cancer

Recruiting at 1 trial location

Overseen By Tara McPartland

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: QT prolonging drugs

Disqualifiers: Ulcerative colitis, Connective tissue disease, 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: Unknown

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of Relugolix, a hormone therapy, combined with precise radiation therapy, SBRT, for prostate cancer. Patients with specific Gleason scores and PSA levels are suitable candidates. The trial aims to determine if this combination treatment reduces cancer markers more effectively and has fewer side effects on sexual and hormonal health compared to SBRT alone. Participants will be randomly assigned to either treatment to allow researchers to compare outcomes accurately. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using medications that cause QT prolongation (a heart rhythm condition). It's best to discuss your current medications with the study team.

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

Previous studies have shown Relugolix to be safe. In a year-long study, patients with advanced prostate cancer took Relugolix alongside other medications, and the results indicated it was well-tolerated. Real-world data also support this, revealing no new safety concerns for its use.

Research on Stereotactic Body Radiotherapy (SBRT) indicates it is generally safe. One study found that using SBRT at a specific dose was safe, with no major issues reported. These findings suggest that both Relugolix and SBRT are generally safe for patients, with no serious side effects commonly reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Relugolix and Stereotactic Body Radiotherapy (SBRT) for prostate cancer because it offers a potentially more effective and convenient approach compared to traditional treatments like surgery or long-term hormone therapy. Relugolix is a novel oral medication that targets hormone pathways more precisely, potentially leading to fewer side effects than injectable hormone therapies. SBRT delivers high doses of radiation in fewer sessions, which might reduce the overall treatment burden and improve patient quality of life. This combination could mean quicker, more targeted treatment with less disruption to daily life, making it an exciting option for advancing prostate cancer care.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that relugolix effectively treats prostate cancer. In studies, over 90% of patients experienced a lasting drop in testosterone, crucial for controlling the disease. Real-world evidence indicates that more than 98% of patients reached the necessary hormone levels. Research has found that stereotactic body radiotherapy (SBRT) offers excellent long-term control of prostate cancer with few side effects. SBRT, similar to other standard treatments, shows good results for patients with low- to intermediate-risk prostate cancer. In this trial, one arm will combine relugolix with SBRT to improve treatment by addressing cancer in different ways, while another arm will study SBRT alone. ^{5 6 7 8 9}

Who Is on the Research Team?

James B. Yu

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Men aged 18+ with specific types of prostate cancer (cFIR/cgUIR) can join. They must have a Gleason score of 3+4 with PSA <20 ng/mL or Gleason 6 and PSA between >10 and <20 ng/mL. Excluded are those on recent investigational drugs, with heart issues like long QT syndrome, history of surgical castration, prior prostate cancer treatments, certain medication use, allergies to relugolix, inflammatory bowel diseases, connective tissue diseases or if GNRH/SBRT therapy is not suitable.

Inclusion Criteria

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Exclusion Criteria

History of long QT syndrome documented in the medical record

You have had allergic reactions to relugolix in the past.

Treatment with another investigational drug or other intervention within 30 days of enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SBRT and Relugolix or SBRT alone. Relugolix is administered for 30 days, starting 14 to 17 days prior to the first SBRT treatment.

6 weeks

Multiple visits for SBRT sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life assessments and PSA monitoring.

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Relugolix
• SBRT

Trial Overview This trial tests the effectiveness and safety of SBRT alone versus SBRT combined with an oral drug called Relugolix in treating cFIR/cgUIR prostate cancer. It aims to see if combining these treatments improves PSA levels better than SBRT alone and assesses their impact on sexual and hormonal function at six months.

How Is the Trial Designed?

Group I: Relugolix and SBRT Active Control 2 Interventions

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.

Group II: Stereotactic body radiotherapy Active Control 1 Intervention

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.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study of 437 patients with localized prostate cancer treated with stereotactic body radiotherapy (SBRT), the treatment showed minimal genitourinary and gastrointestinal toxicities, with no severe adverse effects reported.

The two-year biochemical disease-free survival (bDFS) rate was an impressive 96.1% overall, with even higher rates of 99.0% for low-risk patients, indicating that SBRT is an effective treatment option for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Clinically Localized Prostate Cancer: Toxicity and Biochemical Disease-Free Outcomes from a Multi-Institutional Patient Registry. Davis, J., Sharma, S., Shumway, R., et al.[2022]

Stereotactic body radiation therapy (SBRT) resulted in significantly lower post-treatment PSA levels compared to intensity-modulated radiation therapy (IMRT) at 2 and 3 years, indicating better efficacy in controlling prostate cancer.

Both SBRT and IMRT showed similar overall survival rates after 5 years, but SBRT offers advantages such as lower cost and easier application, making it a suitable alternative for treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy versus conventional intensity-modulated radiation therapy for the treatment of prostate cancer]. Gao, QN.[2022]

In a study of 87 men undergoing stereotactic body radiation therapy (SBRT) for prostate cancer, those who received SpaceOAR hydrogel experienced significantly fewer lower urinary tract symptoms (LUTS) compared to those who did not, with urinary frequency reported in 38% of the SpaceOAR group versus 68% in the non-SpaceOAR group.

The use of α-inhibitors, a medication to manage urinary symptoms, was notably higher in the non-SpaceOAR group throughout the treatment and follow-up period, indicating that SpaceOAR may help reduce the need for additional medication to manage LUTS post-SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural history of lower urinary tract symptoms among men undergoing stereotactic body radiation therapy for prostate cancer with and without a Rectal Hydrogel Spacer. Alshak, MN., Eidelberg, A., Diaz, SM., et al.[2022]

In a study of 120 patients with intermediate- and high-risk prostate cancer, PSMA/MRI-guided stereotactic body radiation therapy (SBRT) with a focal boost to 45 Gy showed promising efficacy, with a 3-year estimated freedom from biochemical failure of 99% for intermediate-risk and 85% for high-risk patients.

The treatment was associated with low toxicity, as only 8% and 6% of patients reported significant urinary and bowel bother, respectively, and less than 5% expressed significant decision regret regarding their treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Outcomes and Decision Regret Using PSMA/MRI-Guided Focal Boost for Prostate Cancer SBRT. Eade, T., Kneebone, A., Hruby, G., et al.[2022]

In a study of 103 patients undergoing stereotactic body radiation therapy (SBRT) for localized prostate cancer, 52% experienced a significant decline in bowel-related quality of life within one week, while 27.5% developed grade 2 or higher rectal toxicity.

Key dosimetric predictors of acute rectal toxicity were identified, specifically rectal D19% and V20Gy, which can help clinicians adjust treatment plans to reduce the risk of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of acute bowel toxicity after Stereotactic Body Radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. Repka, MC., Carrasquilla, M., Paydar, I., 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 comparing two SABR treatments for prostate cancer, patients receiving 40 Gy (pHART6) had similar biochemical relapse-free survival rates to those receiving 35 Gy (pHART3), indicating that higher doses do not compromise effectiveness over time.

However, patients in the pHART6 group experienced a higher incidence of grade 2 genitourinary and gastrointestinal toxicities, suggesting that while the treatment is effective, it may come with increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials. Musunuru, HB., Quon, H., Davidson, M., et al.[2018]

In a study involving 344 high-risk prostate cancer patients with a median follow-up of 49.5 months, stereotactic body radiation therapy (SBRT) demonstrated a high 4-year biochemical recurrence-free survival rate of 81.7% and distant metastasis-free survival rate of 89.1%.

The treatment showed a favorable safety profile, with low incidences of late grade ≥3 genitourinary (2.3%) and gastrointestinal (0.9%) toxicities, indicating that SBRT is both effective and safe for high-risk prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients. van Dams, R., Jiang, NY., Fuller, DB., et al.[2022]

Both RapidArc and Multiplan techniques can effectively deliver a simultaneous integrated boost of 47.5 Gy to intra-prostatic tumor nodules while treating the whole prostate, showing promise for improved local control in prostate cancer.

RapidArc plans resulted in lower mean rectal doses compared to Multiplan, but increasing margins to account for patient movement during treatment led to a significant increase in missed dose constraints, highlighting the need for precise tracking during hypofractionated treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate stereotactic body radiotherapy with simultaneous integrated boost: which is the best planning method? Tree, A., Jones, C., Sohaib, A., et al.[2022]

In a study of 101 patients with higher-risk localized prostate cancer, combining high-dose-rate (HDR) brachytherapy with stereotactic body radiation therapy (SBRT) resulted in a very low incidence of severe toxicities, with no grade ≥3 toxicities observed and only 0.99% experiencing grade 2 gastrointestinal issues.

The treatment showed promising efficacy, with a 2-year biochemical relapse-free survival rate of 97%, indicating strong cancer control outcomes alongside a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer. Gorovets, D., Hopkins, M., Kollmeier, M., et al.[2021]

Stereotactic body radiotherapy (SBRT) is effective for treating localized and metastatic prostate cancer, as prostate cancer shows increased sensitivity to higher radiation doses due to its low α/β ratio.

There is potential for combining SBRT with systemic therapies like androgen deprivation therapy (ADT) and immunotherapy, as SBRT may enhance immune responses, making it a promising area for ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. Adorno Febles, VR., Blacksburg, S., Haas, JA., et al.[2020]

In a study of 24 patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT), the treatment showed a high 24-month prostate-specific antigen relapse-free survival rate of 95.8%.

The use of a high-dose avoidance zone (HDAZ) during SBRT resulted in low rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicities, with no severe (grade ≥3) toxicities reported, indicating a safe approach to dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes. Kotecha, R., Djemil, T., Tendulkar, RD., et al.[2022]

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. 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 ...

3. 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 ...

4. 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.

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39436909/

Adverse events analysis of Relugolix (Orgovyx®) for ... This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx®) using data from the FAERS database, and gain a better understanding of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04666129

NCT04666129 | Study of Relugolix in Men With Metastatic ... This study is being conducted to assess the safety and tolerability of relugolix with other agents approved for use in combination with androgen deprivation ...

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158172-asco-gu-2025-safety-and-tolerability-of-relugolix-in-combination-with-abiraterone-or-apalutamide-for-treatment-of-advanced-prostate-cancer-data-from-a-52-week-clinical-trial.html

ASCO GU 2025: Safety and Tolerability of Relugolix in ... In this 52-week study, the oral testosterone-lowering drug relugolix was studied in patients with advanced prostate cancer in combination with ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.85

Real-world experience on tolerability and safety of ... The combination has a favorable safety and tolerability profile with no new safety concerns. No new DDI concerns were raised.