NCT06922318

The COSMYC Trial (COmbined Suppression of MYC)

A Phase II Study of Sequential Bipolar Androgen Therapy and ZEN-3694 in Sequence With Enzalutamide + ZEN-3694 in Asymptomatic Patients With Metastatic CRPC: The COSMYC Trial (COmbined Suppression of MYC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research is being done to determine if receiving the combination of testosterone and ZEN-3694 followed by the combination of enzalutamide plus ZEN-3694 will decrease the size of tumors in patients with prostate cancer that has become resistant to castration and other therapies. The investigators also want to determine if dosing first with the combination of testosterone and ZEN-3694 may cause enzalutamide and ZEN-3694 to work more effectively.

Detailed description

The primary objectives of the study are first to determine if treatment with the combination of ZEN-3694 and Bipolar Androgen Therapy (i.e. BATZEN) will improve the progression-free survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) compared with historical controls. The second primary objective is to determine if treatment with ZEN-3694 and Enzalutamide (i.e. ZENZA) after progression on Bipolar Androgen Therapy (BAT) will improve PSA-progression-free survival compared to historical controls. Asymptomatic patients with mCRPC without pain due to prostate cancer will be treated on an open label study to evaluate effectiveness of sequential treatment with the combination of ZEN-3694 and high dose testosterone in sequence with enzalutamide and ZEN-3694 to improve primary and secondary outcomes. Eligible patients are those with mCRPC who have progressive disease after treatment with a second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) used as treatment for castration-sensitive or castration-resistant disease. Patients will continue on Androgen Deprivation Therapy (ADT) with LHRH agonist (i.e. Zoladex, Trelstar, Eligard, or Lupron) or LHRH antagonist (Degarelix or Relugolix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production. One cycle of treatment will be 28 days.

Conditions

• Metastatic Castration-resistant Prostate Cancer

Interventions

Type	Name	Description
DRUG	ZEN-3694	One ZEN-3694 pill (48 mg) will be taken each day of each BATZEN cycle.
DRUG	Testosterone cypionate	On day 1 of each BATZEN cycle testosterone cypionate (400 mg) injection to the buttocks will be administered.
DRUG	Enzalutamide	Enzalutamide 160 mg (four 40 mg capsules) taken daily by mouth on each ZENZA cycle.
DRUG	Luteinizing hormone-releasing hormone (LHRH) analogue	Patients will continue on ADT with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonist (Degarelix or Relugolix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production.

Timeline

• Start date: 2025-08-19
• Primary completion: 2031-08-30
• Completion: 2031-08-30
• First posted: 2025-04-10
• Last updated: 2025-09-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study