NCT06059118

Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer

Repeat Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Asymptomatic Patients With Metastatic Castration-Resistant Prostate Cancer: The APEX (Androgen and Polyamine Elimination Alternating With Xtandi) Trial

• 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

Asymptomatic patients with metastatic castrate resistant prostate cancer (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 difluoromethylornithine (DFMO) and high dose testosterone in sequence with enzalutamide to improve primary and secondary outcomes.

Detailed description

Eligible patients are those with mCRPC who have progressive disease after treatment with Abiraterone (Abi) used as treatment for castration-sensitive or castration-resistant disease. Patients will continue on androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (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 119 days and will involve: 1. 7 days of DFMO at a dose of 1000 mg PO BID (D1-D7), followed by 2. 56 days of combined testosterone and DFMO (testosterone cypionate 400 mg IM on D8 and D36 with continued DFMO 1000 mg PO BID) (D8-D63), followed by 3. 56 days of enzalutamide (enzalutamide 160 mg PO daily) (D64-D119) Patients will receive repeat cycles of treatment until clinical or radiographic progression or toxicity requiring drug cessation.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	DFMO	Each 119 day cycle, Days 1-7 patient will take 1000 mg by mouth (PO) twice a day (bid), and then on Day 8 - 63 patient will take 1000 mg PO bid while receiving high dose testosterone IM on Day 8 and Day 36 of cycle.
DRUG	testosterone cypionate	On Day 8 and Day 36 of each 119 day cycle, patient will receive high dose testosterone at 400 mg through intramuscular (IM) injection.
DRUG	Luteinizing hormone-releasing hormone (LHRH) analogue	Patients who have progressive disease after treatment with Abiraterone (Abi) will continue with androgen depravation therapy (ADT) with LHRH analogue (LHRH agonist drug (i.e. Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonist drug (Degarelix or Relugolix)). Dosing instructions will vary between the different LHRH analogues. Patients should follow the dosing instructions as directed by their physician.
DRUG	Enzalutamide	Each 119 day cycle, Days 64-119 patient will take 160 mg by mouth (PO) once a day (qd).

Timeline

• Start date: 2023-10-04
• Primary completion: 2027-01-04
• Completion: 2029-11-30
• First posted: 2023-09-28
• Last updated: 2026-01-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study