RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistant (The RESTORE Study) (Restore)
Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide or abiraterone in men with metastatic CRPC who previously progressed on either of these agents. The study will enroll two cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A); and men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B).
Drug: Testosterone cypionate
Drug: Testosterone Enanthate
Drug: Abiraterone acetate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study to Determine Sequential Response to Bipolar Androgen Therapy (BAT) Followed by Enzalutamide or Abiraterone Post-BAT in Men With Prostate Cancer Progressing on Combined Androgen Ablative Therapies|
- PSA response to Bipolar Androgen Therapy [ Time Frame: On average at 18 months ] [ Designated as safety issue: Yes ]PSA response to BAT (≥50% PSA reduction from pre-BAT baseline level).
- PSA response to enzalutamide or abiraterone acetate post Bipolar Androgen Therapy [ Time Frame: On average at 24 months ] [ Designated as safety issue: No ]PSA response to enzalutamide or abiraterone acetate post-BAT (≥50% PSA reduction from baseline PSA level obtained at initiation of enzalutamide or abiraterone acetate post-BAT)
- PSA progression on enzalutamide or abiraterone acetate post-BAT [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Time to PSA progression on enzalutamide or abiraterone acetate post-BAT
- PSA progression on BAT (Bipolar Androgen Therapy ) [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Time to PSA progression on BAT
- Measurable disease response [ Time Frame: On average at 18 months ] [ Designated as safety issue: Yes ]
Measurable disease response post-BAT and post-treatment with enzalutamide or abiraterone acetate post-BAT.
- For soft tissue lesions, based on RECIST 1.1.
- For bone disease, based on PCWG2 criteria.
- initiation of docetaxel chemotherapy [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Time to initiation of docetaxel chemotherapy
- Quality of life [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]The following quality of life surveys will be administered: FACIT-F, RANDSF-36, Brief Pain Inventory, IIEF and PANAS,
- Safety and Tolerability [ Time Frame: On average at 18 months ] [ Designated as safety issue: Yes ]Adverse events will be collected at each clinic visit and classified for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
- Fasting glucose [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Fasting blood glucose level
- hemoglobin A1c [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]hemoglobin A1c level
- Fasting insulin [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Fasting insulin levels
- Serum N-telopeptide [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Serum N-telopeptide levels
- Osteocalcin [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]Osteocalcin levels
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||April 2019|
|Estimated Primary Completion Date:||April 2019 (Final data collection date for primary outcome measure)|
Experimental: Post-abiraterone or post-enzalutamide
Men with castration-resistant prostate cancer who have progressed on either abiraterone or enzalutamide will be enrolled to this arm. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with either abiraterone 1000 mg by mouth daily or enzalutamide 160 mg by mouth daily, depending on which drug they previously received.
Drug: Testosterone cypionate
DEPO-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. DEPO-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.
Other Name: DEPO-Testosterone InjectionDrug: Testosterone Enanthate
Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
Other Name: DelatestrylDrug: Abiraterone acetate
Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate.
Other Name: ZytigaDrug: Enzalutamide
XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides.
Other Name: Xtandi
The trial will enroll up to 60 patients, 30 for each cohort. Eligible patients will continue on androgen ablative therapy with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) if not surgically castrated to suppress endogenous testosterone production. Patients will also receive intramuscular injection with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dosing scheme was designed to produce rapidly fluctuating serum testosterone levels from the supraphysiologic to the near-castrate range (i.e. Bipolar Androgen Therapy [BAT]). Assessments for response to testosterone will be made approximately every 3 months. Upon displaying evidence of progression, patients will then go on to receive either abiraterone or enzalutamide (whichever agent they had previously progressed on prior to study enrollment).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02090114
|Contact: Avery Spitzfirstname.lastname@example.org|
|Contact: Rana Sullivanemail@example.com|
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Avery Spitz 410-502-2043 firstname.lastname@example.org|
|Contact: Rana Sullivan 410-614-6337 email@example.com|
|Principal Investigator: Samuel Denmeade, MD|
|Principal Investigator:||Samuel Denmeade, MD||Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center|