Hormone Therapy + Radiation vs. Radiation Alone for Prostate Cancer

Overseen By Nina Yang, RN

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 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: 5

Duration: 6 months

392 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining hormone therapy with radiation is more effective than radiation alone for treating prostate cancer. It targets patients with unfavorable intermediate-risk prostate cancer, a type more prone to growth and spread. Participants will receive either hormone therapy (using drugs such as Leuprolide, Degarelix, or Relugolix) with radiation or just radiation, aiming to determine which option provides better tumor control. Men diagnosed with this specific type of prostate cancer who meet other health criteria may be suitable for the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in prostate cancer treatment.

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.

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

Studies have shown that leuprolide and degarelix are generally safe but can affect the heart. In one study, 5.1% of patients taking degarelix and 10.2% of those on leuprolide experienced heart-related issues over a year, suggesting that degarelix might be gentler on the heart than leuprolide. Both drugs are already used to treat prostate cancer.

Relugolix, a daily pill approved for prostate cancer, might cause fewer heart problems than leuprolide. For all these treatments, discussing any heart conditions with a doctor is important.

Stereotactic body radiation therapy (SBRT) is a precise type of radiation treatment that targets cancer while trying to protect healthy tissue. SBRT is generally well-tolerated, though some people may feel tired or notice minor skin changes.

In summary, all treatments have some risks but are generally considered safe. Always consult with a healthcare provider to understand the best option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine hormone therapy with stereotactic body radiation therapy (SBRT) in a novel way. Unlike standard treatments that often rely solely on radiation or long-term hormone therapy, this approach uses drugs like Leuprolide, Degarelix, or Relugolix to temporarily block hormones that fuel cancer growth before administering targeted radiation. This combination could potentially enhance the effectiveness of radiation by shrinking tumors beforehand, offering a more precise attack on cancer cells. Additionally, with SBRT’s ultra-fractionated method, patients receive fewer, more intense doses of radiation, which might mean faster treatment times and reduced side effects.

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

This trial will compare the effectiveness of hormone therapy combined with radiation versus radiation alone for prostate cancer. Research has shown that adding hormone therapy, such as Leuprolide, Degarelix, or Relugolix, to radiation treatment can be effective for prostate cancer. Specifically, Relugolix quickly and consistently lowers testosterone levels, which is crucial for treating prostate cancer. Men who took Relugolix regained their testosterone levels more effectively than those who took Leuprolide. Studies indicate that Leuprolide and Degarelix also slow cancer growth effectively, offering similar benefits. Overall, combining these hormone therapies with radiation may improve treatment outcomes for men at higher risk of prostate cancer. Participants in this trial will receive either hormone therapy with radiation or radiation alone. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael Zelefsky

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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 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

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

In a study of 134 prostate cancer patients switched from leuprolide to degarelix, testosterone and PSA levels remained effectively suppressed, indicating sustained treatment efficacy over the first 3 months.

The safety profile was comparable to leuprolide, with only minor injection site reactions reported, suggesting that switching to degarelix is a safe option for patients.

NCBI (Pubmed)

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. de la Rosette, J., Davis, R., Frankel, D., et al.[2013]

In the phase III HERO trial, relugolix demonstrated a sustained castration rate of over 90% in men with advanced prostate cancer over 48 weeks, which was non-inferior to the traditional treatment with leuprolide, and showed potential superiority in exploratory analyses.

Relugolix is generally well tolerated and may have a lower risk of major adverse cardiac events compared to leuprolide, making it a promising oral treatment option for rapid testosterone suppression without the initial surge associated with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. Shirley, M.[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]

Degarelix is a novel hormonal therapy for prostate cancer that works by antagonizing the GnRH receptor, providing similar oncological outcomes to traditional GnRH agonists.

Unlike GnRH agonists, degarelix avoids the initial flare-up phase and has fewer side effects, making it a potentially more effective option for relieving lower urinary tract symptoms (LUTS) in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of degarelix on LUTS (Lower urinary tract symptoms) relief in patients with prostate cancer]. Bertaccini, A., Marchiori, D.[2017]

Degarelix is as effective as leuprolide in suppressing testosterone levels in patients with advanced prostate cancer, with faster results and no testosterone surges, based on a 12-month phase III study.

The drug is generally well tolerated, with mild to moderate side effects, making it a viable treatment option for patients needing endocrine therapy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Degarelix: a review of its use in patients with prostate cancer. Carter, NJ., Keam, SJ.[2021]

In a study involving 1074 men with advanced prostate cancer, relugolix demonstrated similar castration resistance-free survival (CRFS) rates compared to leuprolide, with rates of 74.3% and 75.3% respectively after 48 weeks of treatment.

No new safety concerns were identified with relugolix, indicating that it is a safe alternative to leuprolide for managing advanced prostate cancer.

NCBI (Pubmed)

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. Saad, F., George, DJ., Cookson, MS., et al.[2023]

Relugolix, an oral GnRH antagonist, effectively reduces testosterone levels in men with advanced prostate cancer without causing the initial testosterone flare associated with GnRH agonists like leuprolide acetate.

In the HERO Phase III trial, relugolix not only provided faster and more sustained testosterone suppression but also resulted in a 54% lower incidence of major adverse cardiovascular events compared to leuprolide acetate, highlighting its safety advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix, an oral gonadotropin-releasing hormone antagonist for the treatment of prostate cancer. George, DJ., Dearnaley, DP.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571668/

Relugolix vs. Leuprolide Effects on Castration Resistance ... Relugolix treatment was also associated with a 54% risk reduction in MACE when compared to men receiving leuprolide treatment. Based on the ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056810

Cardiovascular Safety of Degarelix Versus Leuprolide in ... A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004325

Oral Relugolix for Androgen-Deprivation Therapy in ... Treatment adherence with oral relugolix was more than 99% and similar to that of injectable leuprolide. These findings are consistent with reported real-world ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2588931123002900

Testosterone Recovery for Relugolix Versus Leuprolide in ... Compared with leuprolide acetate, more men treated with relugolix achieved ≥80% of baseline testosterone levels (39% vs 2.1%). Men ≤65 yr and those with ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8536955/

Real-world Cardiovascular Outcomes Associated With ... A total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2785390

Cardiovascular Outcomes With Degarelix vs Leuprolide as ... Comparing Cardiovascular Outcomes With Degarelix or Leuprolide as Prostate Cancer Therapy—Applying Real-world Data to Clinical Trial Emulation.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02663908

Study Details | NCT02663908 | A Trial Comparing ... The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S258893112400213X

Comparative Cardiovascular Safety of Gonadotropin ... Slovin, et al. Cardiovascular safety of degarelix versus leuprolide in patients with prostate cancer: the primary results of the PRONOUNCE randomized trial.