Opevesostat for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+276 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Androgen deprivation therapy

Must not be taking: Anticancer mAbs, Herbal products

Disqualifiers: Gastrointestinal disorder, Diabetes, Cardio/cerebro-vascular disease, Seizure history, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a phase 3, randomized, open-label study of opevesostat compared to alternative abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer (mCRPC) with respect to overall survival (OS) and to radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria In Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) in participants with mCRPC previously treated with next-generation hormonal agent (NHA) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior with respect to OS and rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop using herbal products with hormonal activity, 5-αreductase inhibitors, and certain other medications like strong CYP3A4 inducers and P-gp inhibitors at least 2-4 weeks before starting the study.

What data supports the effectiveness of the drug Opevesostat for prostate cancer?

Research shows that abiraterone acetate, often used with prednisone, improves survival in patients with metastatic castration-resistant prostate cancer. Additionally, combining abiraterone with enzalutamide and androgen deprivation therapy has been shown to improve outcomes for these patients. ^{1 2 3 4 5}

Is Opevesostat safe for humans?

Abiraterone acetate, a component of Opevesostat, has been used safely in combination with other drugs for treating prostate cancer, but it may increase the risk of metabolic (related to the body's chemical processes) and cardiovascular (heart and blood vessel) issues. ^{1 2 5 6 7}

What makes the drug Opevesostat for prostate cancer unique?

Opevesostat, combined with Abiraterone acetate and Enzalutamide, offers a novel approach by potentially enhancing the effectiveness of existing prostate cancer treatments. This combination targets different pathways involved in cancer progression, which may improve outcomes compared to using these drugs individually. ^{1 2 5 8 9}

Eligibility Criteria

This trial is for men with advanced prostate cancer that has spread and resisted treatment, including hormone therapy and up to two chemo treatments. Participants must have a specific performance status, which measures how well they can do daily activities, and cannot have small cell prostate cancer histology.

Inclusion Criteria

My prostate cancer is confirmed without being a small cell type.

My prostate cancer got worse while on hormone therapy or after surgery to remove my testicles, within the last 6 months.

My cancer has spread, as shown by bone scan or CT/MRI.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive opevesostat or alternative NHA until progression

Up to 54 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 54 months

Treatment Details

Interventions

• Abiraterone acetate (Hormone Therapy)
• Dexamethasone (Corticosteroid)
• Enzalutamide (Hormone Therapy)
• Fludrocortisone acetate (Corticosteroid)
• Hydrocortisone (Corticosteroid)
• MK-5684 (Other)
• Prednisone (Corticosteroid)

Trial Overview The study compares MK-5684 to other medications like abiraterone acetate or enzalutamide in improving survival without cancer progression. It's open-label, meaning everyone knows what treatment they're getting, and it uses imaging reviews by experts who don't know the patients' group assignments.

Participant Groups

Group I: Opevesostat Experimental Treatment 4 Interventions

Participants receive opevesostat 5 mg by oral tablets twice daily (bid) plus dexamethasone 1.5 mg by oral tablets once daily (qd) and 0.1 mg fludrocortisone acetate by oral tablet qd until progression. Hydrocortisone 100 mg (oral or intramuscular \[IM\]) dose will also be provided to participants for use as rescue medication.

Group II: Abiraterone Acetate or Enzalutamide Active Control 3 Interventions

Participants receive abiraterone 1000 mg qd by oral tablets plus prednisone 5 mg bid by oral tablets or enzalutamide 160 mg qd by oral tablets.

Abiraterone acetate is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

🇺🇸 Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

🇨🇦 Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

🇯🇵 Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Metro-Minnesota Community Clinical Oncology ( Site 0014) Saint Louis Park, MN

University of Kentucky Chandler Medical Center ( Site 0048) Lexington, KY

Baltimore Veterans Affairs Medical Center ( Site 0069) Baltimore, MD

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer Sherbrooke, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC Lead Sponsor

Orion Corporation, Orion Pharma Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023] Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021] Oral abiraterone acetate (Zytiga®), a selective cytochrome P450 17A1 enzyme inhibitor, is used in combination with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. In a clinical trial in patients with CRPC, abiraterone acetate plus prednisone significantly prolonged overall survival, the time to prostate-specific antigen progression and progression-free survival compared with placebo plus prednisone.

3. England pubmed.ncbi.nlm.nih.gov

Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). [2023] Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown.

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

Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment. [2022] Enzalutamide (Enz) and abiraterone acetate (AA) are hormone treatments that have a proven survival advantage in patients with metastatic, castration-resistant prostate cancer who previously received docetaxel (Doc). Recently, limited activity of AA after Enz and of Enz after AA was demonstrated in small cohort studies. Here, the authors present the activity and tolerability of Enz in patients who previously received AA and Doc in the largest cohort to date.

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022] Abiraterone acetate is a highly variable drug and has been approved for the treatment of patients with metastatic castration-resistant prostate cancer in many countries. This study was conducted to compare the pharmacokinetic profile between the test product (abiraterone acetate tablet) and reference product ZYTIGA® (250 mg) mainly.

6. 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] Abiraterone and enzalutamide are the most common oral agents for the treatment of men with advanced prostate cancer. To understand their safety profiles in real-world settings, we examined the association between the use of abiraterone or enzalutamide and the risk of metabolic or cardiovascular adverse events while on treatment.

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

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020] To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI(®)) in metastatic castration-resistant prostate cancer.

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

Adoption of Abiraterone and Enzalutamide by Urologists. [2021] To investigate the adoption of abiraterone and enzalutamide by urologists. Abiraterone and enzalutamide are oral therapies approved for the treatment of metastatic castration-resistant prostate cancer, a disease most commonly treated by medical oncologists.

9. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020] Abiraterone acetate, marketed as Zytiga®, is an antiandrogen medication used in the treatment of prostate cancer. Abiraterone acetate is a BCS Class IV compound associated with several oral delivery challenges. Its low solubility and high lipophilicity lead to poor oral bioavailability (