Relugolix + Enzalutamide for Prostate Cancer

Overseen By Kelly Stratton, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Must be taking: Relugolix, Enzalutamide

Disqualifiers: Cardiac event, Metastatic cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for advanced prostate cancer using two medications: relugolix (a hormone therapy) and enzalutamide (an anti-androgen medication). The researchers aim to determine if these medications, when combined with standard treatments like surgery or radiation, can better control the cancer, improve cure rates, and extend the time patients live without cancer progression. Men diagnosed with high-risk advanced prostate cancer, who are candidates for surgery or radiation and do not have distant cancer spread, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment approach.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of relugolix and enzalutamide is generally well-tolerated by patients. One study demonstrated that this combination led to a lasting drop in prostate-specific antigen (PSA) levels, a marker used to monitor prostate cancer. Importantly, patients did not experience severe side effects, indicating the combination was well tolerated. Another study found that using relugolix alone or with enzalutamide had similar safety results, suggesting it is safe to use both together.

These findings suggest that while side effects can occur, they are usually manageable. As this trial is in the early stages, the main goal is to further explore safety and effectiveness. However, the current data appears promising for those considering joining the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about combining relugolix and enzalutamide for prostate cancer because it offers a new approach to hormone therapy. Unlike traditional androgen deprivation therapies (ADTs) that often involve injections or surgical removal of the testes, relugolix is an oral medication that blocks testosterone production more directly and quickly. Combined with enzalutamide, which prevents cancer cells from using any remaining testosterone, this duo could provide a more comprehensive blockade of the hormones that fuel prostate cancer growth. This combination has the potential to enhance treatment effectiveness while also offering the convenience of oral administration, which is a significant shift from the standard injection-based therapies.

What evidence suggests that the combination of relugolix and enzalutamide might be an effective treatment for advanced prostate cancer?

Research has shown that combining relugolix and enzalutamide might effectively treat advanced prostate cancer. In this trial, participants will receive this combination therapy. One study found that this combination led to a lasting drop in PSA levels, a marker doctors use to monitor prostate cancer, indicating effective cancer control. Additionally, most patients tolerated the treatment with minimal side effects. These findings suggest that using relugolix and enzalutamide together could help slow cancer growth and improve patient health. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for men over 18 with advanced prostate cancer who can consent to treatment, have a life expectancy of at least 6 months, and normal organ function. They must be able to perform daily activities (ECOG status 0-2) and agree to use contraception during the study.

Inclusion Criteria

You are expected to live for at least 6 months.

My blood, liver, and kidney tests are normal.

I am able to get out of my bed or chair and move around.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with relugolix and enzalutamide for 6 months

24 weeks

Local-regional Treatment

Participants undergo Radiation Therapy or prostatectomy as part of their cancer treatment

4-6 weeks

Adjuvant Treatment

Participants continue with adjuvant therapy with relugolix and enzalutamide for an additional 18 months

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Relugolix + Enzalutamide

Trial Overview The study tests the effectiveness and safety of combining relugolix with enzalutamide in treating high-risk advanced prostate cancer. It aims to see if this combo increases cure rates and extends the time patients live without their cancer worsening.

How Is the Trial Designed?

Group I: Prostate Cancer Combo Therapy Trial Experimental Treatment 1 Intervention

A single-arm Phase Ib study explores the effectiveness and safety of neoadjuvant and adjuvant hormonal therapy combining relugolix and enzalutamide in high-risk locally advanced prostate cancer patients eligible for ADT followed by radiation therapy or surgery.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

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

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Published Research Related to This Trial

In preclinical models of metastatic castration-resistant prostate cancer, the combination of NLG207 (a HIF-1α inhibitor) and enzalutamide significantly reduced tumor volume by 93% after 3 weeks, indicating strong efficacy against enzalutamide resistance.

The addition of NLG207 enhanced the effectiveness of enzalutamide, decreasing the median tumor growth rate by 51%, suggesting that targeting both HIF-1α and androgen receptor pathways could be a promising strategy for overcoming treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models. Schmidt, KT., Chau, CH., Strope, JD., et al.[2022]

In a study of 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: [e-mail]. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. Trump, D.[2018]

In a phase 2 study involving 67 men with hormone-naive prostate cancer, 92.5% experienced an 80% or greater decline in prostate-specific antigen (PSA) levels after 25 weeks of treatment with enzalutamide, indicating strong efficacy in disease suppression.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although some patients experienced grade 3 adverse events like pneumonia and hypertension, which were not deemed treatment-related.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

The PREVAIL Phase 3 trial demonstrated that enzalutamide significantly improves radiographic-progression free survival in men with castration-resistant prostate cancer (CRPC), with 65% of patients showing no progression compared to those on placebo.

Enzalutamide also provided a median overall survival benefit of 32.4 months versus 30.2 months for the placebo group, indicating its efficacy as a treatment option before chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for treatment of CRPC: rationale for sequencing and potential clinical biomarker for resistance. Lochrin, SE., Figg, WD., Finn, SP.[2020]

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 men with metastatic hormone-sensitive prostate cancer, enzalutamide, when combined with androgen-deprivation therapy, significantly prolonged radiographic progression-free survival compared to a placebo.

This finding highlights the efficacy of enzalutamide as an androgen-receptor inhibitor in improving outcomes for patients undergoing treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

In a study of 129 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide, nearly half (around 49-51%) showed significant declines in PSA levels at various time points, indicating a positive response to the treatment.

The study found that a decline in PSA levels was a significant predictor of improved overall survival, particularly notable at 12 weeks, supporting the use of PSA responses as a valuable prognostic marker in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSA declines and survival in patients with metastatic castration-resistant prostate cancer treated with enzalutamide: A retrospective case-report study. Bosso, D., Pagliuca, M., Sonpavde, G., et al.[2022]

In a phase 3 trial involving 1401 men with nonmetastatic, castration-resistant prostate cancer, enzalutamide significantly improved median overall survival to 67.0 months compared to 56.3 months for placebo, indicating a 27% lower risk of death.

The safety profile of enzalutamide was consistent with previous studies, with a similar rate of serious adverse events compared to placebo, primarily involving fatigue and musculoskeletal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. Sternberg, CN., Fizazi, K., Saad, F., et al.[2021]

In a long-term study of 67 patients with hormone-naïve prostate cancer, enzalutamide monotherapy resulted in a 100% prostate-specific antigen (PSA) response rate at 97 weeks for those who remained on treatment, indicating its strong efficacy.

The treatment was well-tolerated with minimal negative effects on total-body bone mineral density, although common side effects included gynecomastia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

In a phase 3 study involving 1717 patients, enzalutamide significantly improved radiographic progression-free survival at 12 months (65% vs. 14% for placebo), demonstrating an 81% risk reduction in disease progression.

Enzalutamide also reduced the risk of death by 29% compared to placebo, with 72% of patients alive at the data cutoff, and delayed the need for chemotherapy and other disease-related events, although it was associated with fatigue and hypertension as common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide in metastatic prostate cancer before chemotherapy. Beer, TM., Armstrong, AJ., Rathkopf, DE., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06130995

NCT06130995 | Relugolix + Enzalutamide Study in High- ... This clinical trial aims to assess the effectiveness and safety of combining relugolix and enzalutamide as neoadjuvant and adjuvant androgen deprivation therapy ...

2. urotoday.com urotoday.com/conference-highlights/scs-aua-2025/scs-aua-2025-prostate-cancer/163061-scs-aua-2025-trial-in-progress-renapca-phase-ib-trial-of-relugolix-and-enzalutamide-as-neoadjuvant-adjuvant-to-local-regional-treatment-in-patients-with-high-risk-locally-advanced-prostate-cancer.html

RENAPCA: Phase IB Trial of Relugolix and Enzalutamide ... This study aims to optimize ADT strategies for high-risk locally advanced prostate cancer, potentially improving patient outcomes. The ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11471072/

Relugolix Plus Enzalutamide For Metastatic Hormone ... Relugolix plus enzalutamide produced a sustained reduction in PSA and the combination was well tolerated. Further research including real world ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S155876732300068X

Impact of Concomitant Prostate Cancer Medications on ... These patients received combination treatment with enzalutamide and relugolix for a mean of 113.1 days (18.0-266.0 days).

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 ...