Hormone Therapy + Radiation vs. Radiation Alone for Prostate Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Michael Zelefsky

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NYU Langone Health

Must be taking: Androgen deprivation

Disqualifiers: Metastatic disease, Positive lymph nodes, Prior prostate cancer treatment, Recent malignancy, Crohn's, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

For this study, unfavorable intermediate risk prostate cancer patients will select whether they are to be treated with the standard of care (SOC) 6 months of Androgen Deprivation Therapy (ADT) in conjunction with stereotactic body radiation therapy/radiosurgery (SBRT) directed to the prostate versus SBRT alone. The patient population will include those with National Comprehensive Cancer Network (NCCN)-defined unfavorable intermediate risk disease. All patients will be followed every 6 months for up to 5 years from the first patient treated and will undergo a routine 24-30 months post-SBRT prostate biopsy to assess for local tumor control.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have been on hormonal therapy for prostate cancer within 30 days before enrolling, you may not be eligible to participate.

What data supports the effectiveness of the drug Relugolix in treating prostate cancer?

Research shows that Relugolix, an oral drug, effectively reduces testosterone levels in men with advanced prostate cancer, maintaining a high rate of testosterone suppression over 48 weeks. It also has a lower risk of major heart-related side effects compared to another drug, leuprolide. ^{1 2 3 4 5}

Is hormone therapy with radiation generally safe for prostate cancer treatment?

Hormone therapy drugs like Relugolix and Leuprolide, used in combination with radiation for prostate cancer, are generally well tolerated and have a safety profile consistent with testosterone suppression. Relugolix may have a lower risk of major heart-related events compared to Leuprolide. ^{1 2 3 6 7}

What makes the treatment with hormone therapy and radiation unique for prostate cancer?

This treatment combines hormone therapy with radiation, using drugs like relugolix, which is an oral medication that quickly reduces testosterone without causing an initial surge, unlike traditional injections. Relugolix also has a lower risk of heart-related side effects and offers the convenience of oral administration, making it a novel option for prostate cancer treatment. ^{1 2 3 5 8}

Eligibility Criteria

This trial is for men with a specific stage of prostate cancer called 'unfavorable intermediate risk.' They should be suitable for hormone therapy and radiation, have no prior treatments for prostate cancer, and be able to undergo biopsies. Specific details on inclusion or exclusion criteria are not provided.

Inclusion Criteria

IPSS ≤ 20

My prostate cancer is intermediate risk with specific Gleason scores or PSA levels.

Serum testosterone ≥ 150 ng/dL determined within 2 months prior to enrollment

Exclusion Criteria

I have Crohn's disease or ulcerative colitis.

My scans show cancer has spread to my bones.

I have not had prostate cancer treatment in the last 30 days, except for certain procedures.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 months of Androgen Deprivation Therapy (ADT) in conjunction with stereotactic body radiation therapy/radiosurgery (SBRT) or SBRT alone

6 months

5 visits (in-person) for SBRT

Follow-up

Participants are monitored for safety and effectiveness every 6 months for up to 5 years, with a routine prostate biopsy at 24-30 months post-SBRT

Up to 5 years

Bi-annual visits (in-person)

Treatment Details

Interventions

• Leuprolide, Degarelix or Relugolix (Hormone Therapy)
• Stereotactic body radiation therapy/radiosurgery (SBRT) (Radiation)

Trial Overview The study compares two approaches: one group receives hormone therapy (ADT) using drugs like Leuprolide, Degarelix, or Relugolix along with targeted radiation (SBRT), while the other group gets only SBRT. Patients will be randomly assigned to these groups and monitored for up to five years.

Participant Groups

Group I: ADT with SBRT Experimental Treatment 2 Interventions

The ADT patients will be treated with monthly Degarelix, or Leuprolide injections or daily Relugolix pills. After three months have elapsed, these patients as per routine will undergo SBRT. SBRT comprises stereotactic, ultra-fractionated radiotherapy every other day for five total treatments.

Group II: SBRT Alone Active Control 1 Intervention

Participants treated with SBRT alone (standard of care) will be administered stereotactic, ultra-fractionated radiotherapy every other day for five total treatments.

Leuprolide, Degarelix or Relugolix is already approved in United States, European Union, United States, European Union, United States, European Union for the following indications:

🇺🇸 Approved in United States as Leuprolide acetate for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

🇪🇺 Approved in European Union as Leuprolide acetate for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

🇺🇸 Approved in United States as Degarelix acetate for:

• Prostate cancer

🇪🇺 Approved in European Union as Degarelix acetate for:

• Prostate cancer

🇺🇸 Approved in United States as Relugolix for:

• Prostate cancer

🇪🇺 Approved in European Union as Relugolix for:

• Prostate cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NYU Langone Health New York, NY

Who Is Running the Clinical Trial?

NYU Langone Health Lead Sponsor

References

1. France pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. [2023] Relugolix (Orgovyx®), an orally active nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist that provides rapid testosterone suppression, is indicated in the USA for the treatment of advanced prostate cancer and in the EU for advanced hormone-sensitive prostate cancer. In the pivotal phase III HERO trial in men with advanced prostate cancer, once-daily oral relugolix (with a loading dose on day 1) led to a sustained castration rate over 48 weeks of treatment of > 90%, a rate that was non-inferior to that provided by intramuscular leuprolide depot every 3 months (with an exploratory analysis further indicating the superiority of relugolix over leuprolide). Relugolix was generally well tolerated, having an adverse event profile that is consistent with testosterone suppression. Furthermore, there is evidence that relugolix may be associated with a lower risk of major adverse cardiac events compared with leuprolide. With the ability to provide the rapid testosterone suppression (with no initial surge in testosterone upon treatment initiation) combined with the benefits of oral administration and potentially improved cardiac safety, relugolix presents a valuable treatment option for men with advanced prostate cancer where androgen deprivation therapy is indicated.

2. 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] External beam radiotherapy (EBRT) with neoadjuvant/adjuvant androgen deprivation therapy (ADT) is an established treatment option to prolong survival for patients with intermediate- and high-risk prostate cancer (PCa). Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was evaluated in this clinical setting in comparison with degarelix, an injectable GnRH antagonist.

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] Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer.

4. New Zealand pubmed.ncbi.nlm.nih.gov

Degarelix: a review of its use in patients with prostate cancer. [2021] Degarelix (Firmagon(®); Gonax(®)) is a gonadotropin-releasing hormone receptor antagonist that is approved for the treatment of advanced (hormone-dependent) prostate cancer in the US and EU and the treatment of prostate cancer in Japan. In a pivotal randomized, controlled, 12-month phase III study, degarelix (initial subcutaneous dose of 240 mg followed by monthly dosages of 80 mg) was noninferior to leuprolide (monthly intramuscular dosages of 7.5 mg) in patients with prostate cancer of any stage for which endocrine treatment was indicated (except neoadjuvant hormonal therapy) with regard to suppression of testosterone to castration levels (i.e. ≤0.5 ng/mL). Suppression of testosterone and prostate-specific antigen (PSA) levels was faster with degarelix than with leuprolide, and no testosterone surges or microsurges were seen in degarelix recipients. Suppression of testosterone and PSA levels was maintained for the 12-month study duration and continued for up to 5 years in an extension to the main trial (including in patients switching from leuprolide to degarelix in the extension). The drug was generally well tolerated, with most adverse events being mild to moderate in severity. Injection-site reactions and events reflecting the expected effects of testosterone suppression (e.g. hot flushes, weight increase) were the most common treatment-emergent adverse events. Thus, degarelix is a useful option for the treatment of prostate cancer in patients for whom endocrine treatment is indicated.

5. England pubmed.ncbi.nlm.nih.gov

Relugolix, an oral gonadotropin-releasing hormone antagonist for the treatment of prostate cancer. [2023] Androgen deprivation therapy using gonadotropin-releasing hormone (GnRH) analogues is standard treatment for intermediate and advanced prostate cancer. GnRH agonist therapy results in an initial testosterone flare, and increased metabolic and cardiovascular risks. The GnRH antagonist relugolix is able to reduce serum testosterone levels in men with prostate cancer without inducing testosterone flare. In the HERO Phase III trial, relugolix was superior to leuprolide acetate at rapidly reducing testosterone and continuously suppressing testosterone, with faster post-treatment recovery of testosterone levels. Relugolix was associated with a 54% lower incidence of major adverse cardiovascular events than leuprolide acetate. As the first oral GnRH antagonist approved for the treatment of advanced prostate cancer, relugolix offers a new treatment option.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Relugolix vs. Leuprolide Effects on Castration Resistance-Free Survival from the Phase 3 HERO Study in Men with Advanced Prostate Cancer. [2023] Background: Relugolix is an oral GnRH receptor antagonist approved for men with advanced prostate cancer. Relugolix treatment has demonstrated an ability to lower testosterone to sustained castration levels in the phase 4 HERO study. Herein, we describe the results of a secondary endpoint of castration resistance-free survival (CRFS) during 48 weeks of treatment and profile patients with castration-resistant prostate cancer (CRPC). Methods: Subjects were 2:1 randomized to either relugolix 120 mg orally once daily (after a single 360 mg loading dose) or 3-monthly injections of leuprolide for 48 weeks. CRFS, defined as the time from the date of first dose to the date of confirmed prostate-specific antigen progression while castrated or death due to any reason was conducted in the metastatic disease population and the overall modified intention-to-treat (mITT) populations. Results: The CRFS analysis (mITT population) included 1074 men (relugolix: n = 717; leuprolide: n = 357) with advanced prostate cancer as well as 434 men (relugolix: n = 290; leuprolide: n = 144) with metastatic prostate cancer. In the metastatic disease populations, CRFS rates were 74.3% (95% CI: 68.6%, 79.2%) and 75.3% (95% CI: 66.7%, 81.9%) in the relugolix and leuprolide groups, respectively (hazard ratio: 1.03 [0.68, 1.57]; p = 0.84) at week 48. Results in the overall mITT population were similar to the metastatic population. No new safety findings were identified. Conclusions: In men with metastatic disease or in the overall population of the HERO study, CRFS assessed during the 48-week treatment with relugolix was not significantly different than standard-of-care leuprolide. Relugolix had similar efficacy for men with/without CRFS progression events.

7. India pubmed.ncbi.nlm.nih.gov

Efficacy and safety of androgen deprivation therapy after switching from monthly leuprolide to monthly degarelix in patients with prostate cancer. [2013] To evaluate whether switching prostate cancer (PCa) patients from leuprolide to degarelix is associated with any change in the efficacy of testosterone suppression or safety profile during the first 3 months.

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

[The efficacy of degarelix on LUTS (Lower urinary tract symptoms) relief in patients with prostate cancer]. [2017] Hormonal therapy is one of the treatment options for prostate cancer patients. There are many hormonal treatments modality to block the testosterone effect on prostate cancer cell proliferation. Degarelix is an innovative molecule able to antagonize the GnRH receptor with comparable oncological results to GnRH agonist, but with less side effects, avoiding the flare up phase, and better efficacy in LUTS relief. These characteristics of degarelix can impact on the clinical decision making to choose a therapy instead of another.