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

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}

Research Team

Michael Zelefsky

Principal Investigator

NYU Langone Health

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.

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
• 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.

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 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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

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

Relugolix: A Review in Advanced Prostate Cancer. [2023]

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]

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]

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

Degarelix: a review of its use in patients with prostate cancer. [2021]

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

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

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]

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]

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]