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
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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.
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…
Eligibility
- Age range
- 18+ years
- Sex
- Male
- Healthy volunteers
- No
Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) Performance status ≤2. 2. Age ≥18 years. 3. Histologically-confirmed adenocarcinoma of the prostate. 4. Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist). 5. Documented castrate level of serum testosterone (\<50 ng/dl). 6. Metastatic disease radiographically documented by CT or bone scan. 7. Must have had disease progression while on abiraterone acetate based on: * PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 w…
Interventions
- DrugDFMO
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.
- Drugtestosterone 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.
- DrugLuteinizing 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.
- DrugEnzalutamide
Each 119 day cycle, Days 64-119 patient will take 160 mg by mouth (PO) once a day (qd).
Location
- Johns Hopkins University: Sidney Kimmel Comprehensive Cancer CenterBaltimore, Maryland