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

Trial Summary

What is the purpose of this trial?

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: 1. Whether the proportion of men who undergo SUGAR have a superior rate of attaining PSA nadir of \<= 0.2 compared to SBRT alone, and 2. 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.

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.

What data supports the effectiveness of the treatment SBRT + Relugolix for prostate cancer?

Research shows that stereotactic body radiation therapy (SBRT) is effective for treating localized and high-risk prostate cancer, with studies indicating good disease-free survival rates and potential benefits when combined with other therapies. Additionally, SBRT has been noted for its ability to enhance immune responses, suggesting it could work well with treatments like Relugolix, which is a hormone therapy used to lower testosterone levels in prostate cancer patients. ^{1 2 3 4 5}

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

The safety of SBRT (Stereotactic Body Radiation Therapy) for prostate cancer has been studied, showing some short-term side effects like urinary and bowel issues, but these are generally manageable. However, there is no specific safety data available for the combination of SBRT with Relugolix (a medication used to lower testosterone levels) in the provided research. ^{1 6 7 8 9}

How is the treatment SBRT + Relugolix for prostate cancer different from other treatments?

SBRT (Stereotactic Body Radiation Therapy) combined with Relugolix is unique because it uses a high-dose, precise form of radiation therapy alongside a drug that lowers testosterone levels, which can enhance the effectiveness of the radiation. This combination may offer a more targeted approach with potentially fewer side effects compared to traditional treatments. ^{2 4 10 11 12}

Research Team

James B. Yu

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

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 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 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]

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]

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]

References

1. United States 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. [2022]

2. Germany 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. [2022]

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

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. [2020]

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

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients. [2022]

6. United States 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. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of acute bowel toxicity after Stereotactic Body Radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. [2023]

9. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Early Outcomes and Decision Regret Using PSMA/MRI-Guided Focal Boost for Prostate Cancer SBRT. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Prostate stereotactic body radiotherapy with simultaneous integrated boost: which is the best planning method? [2022]

12. China pubmed.ncbi.nlm.nih.gov

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