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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test how effective and safe it is to use a combination of two medications, relugolix and enzalutamide, in patients with advanced prostate cancer. We want to see if this combination can help improve the chances of curing the cancer and make the patients live longer without the cancer getting worse. The main questions we want to answer in this study are: * Can using relugolix and enzalutamide together help increase the chances of curing high-risk advanced prostate cancer? * Does this combination treatment help patients live longer without their cancer getting worse? Participants in this study will be asked to take relugolix and enzalutamide as part of their cancer treatment. They will also undergo Radiation Therapy or prostatectomy, which are standard treatments for this type of cancer.

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.

What data supports the effectiveness of the drug Relugolix + Enzalutamide for prostate cancer?

Research shows that enzalutamide, one of the drugs in the combination, helps delay the spread of prostate cancer and improves survival in various stages of the disease. It has been effective in both hormone-sensitive and castration-resistant prostate cancer, suggesting potential benefits when combined with other treatments like Relugolix. ^{1 2 3 4 5}

Is the combination of Relugolix and Enzalutamide safe for humans?

Relugolix is generally well tolerated and may have a lower risk of major heart-related issues compared to some other treatments. Enzalutamide has been associated with some adverse effects, including a risk of severe low platelet count and seizures, as well as potential metabolic and heart-related side effects. ^{6 7 8 9 10}

How does the drug Relugolix + Enzalutamide differ from other prostate cancer treatments?

Relugolix + Enzalutamide is unique because it combines an oral androgen-receptor inhibitor (Enzalutamide) with a new drug (Relugolix) that may offer a different mechanism of action compared to traditional hormone therapies, potentially providing an alternative for patients who have not responded to other treatments. ^{3 5 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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 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 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]

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 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]

References

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

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

2. United States 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. [2022]

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

Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models. [2022]

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

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. [2021]

5. Switzerland 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. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

7. United States 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]. [2018]

8. France pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. [2021]

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

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]

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

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. [2021]

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

Enzalutamide for treatment of CRPC: rationale for sequencing and potential clinical biomarker for resistance. [2020]

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

Enzalutamide in metastatic prostate cancer before chemotherapy. [2022]