In April 2011, the United States Food and Drug Administration (FDA) approved the oral drug abiraterone acetate (Zytiga ®) in combination with prednisone (a steroid) to treat patients with metastatic castration-resistant prostate cancer who have received prior docetaxel (chemotherapy). In December 2012, the FDA approved Zytiga ® in combination with prednisone to treat patients with metastatic castration-resistant prostate cancer who have not received prior chemotherapy. Degarelix (Firmagon ®), a testosterone lowering agent given as a monthly injection, is FDA approved for the treatment of patients with advanced prostate cancer. The purpose of this study is to evaluate abiraterone acetate and prednisone in combination with degarelix as a possible treatment for PSA recurrent prostate cancer as compared to abiraterone acetate alone and degarelix alone. This will be the first time these drugs will be used together.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
Patients randomized to abiraterone acetate and prednisone (Group 1) will be instructed to take 1000 mg (four 250 mg tablets) of abiraterone acetate orally (PO) at least 1 hour before a meal and 2 hours after a meal every day. These patients will also be treated with prednisone 5 mg once daily with food.
Patients randomized to abiraterone acetate plus degarelix and prednisone (Group 2) will be instructed to take 1000 mg (four 250 mg tablets) of abiraterone acetate orally (PO) at least 1 hour before a meal and 2 hours after a meal every day and prednisone 5 mg once daily with food. Patients will also be given two subcutaneous injections of degarelix 120 mg on Cycle 1, Day 1(starting dose) and 80 mg subcutaneous doses (maintenance doses) every 28 days (±3 days) thereafter.
Patients randomized to degarelix alone (Group 3) will be given two subcutaneous injections of degarelix 120 mg on Cycle 1, Day 1 (starting dose) and 80 mg subcutaneous doses (maintenance doses) every 28 days (± 3 days) thereafter.
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Karmanos Cancer Institute, Wayne State University
Detroit, Michigan, United States
Urology Cancer Center and GU Research Network
Omaha, Nebraska, United States
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, United States
Memorial Sloan Kettering West Harrison
Harrison, New York, United States
NorthShore University Health System
Long Island City, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
...and 6 more locations
Progression-free Survival (PFS)
defined as an undetectable PSA (using a routine non-ultrasensitive PSA assay) with non-castrate level of testosterone (\>150 ng/dL) at 18 months from the time of treatment initiation (PSA0).
Time frame: 18 months
Soft Tissue Complete Response
In addition to an undetectable PSA, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (Complete Response per RECIST) in order to meet the criteria for PFS. Outcome in subjects who develop radiographically evident metastatic disease while on study will be considered treatment failures independent of their respective PSA values.
Time frame: 1 year
PSA Response Rate
The percentage of patients with a non-castrate level of testosterone (\>150 ng/dL) and an undetectable PSA at 8 months from PSA0 will be measured.
Time frame: 8 months
Overall Quality of Life
with particular attention to libido, potency, anxiety, depression, hot flashes, and fatigue. Effects of each arm on health-related quality of life will be assessed via PRO Survey (Appendix C) completed on paper by the patient at the following study visits: Up to 30 Days Prior to Randomization, each Day 1 of Treatment Cycle, End of Treatment, and each Post-Treatment Follow-up.Effects of each arm on quality of life,
Time frame: 1 year
Non-hematologic Adverse Events
Safety will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations and clinical laboratory tests throughout the conduct of the study.
Time frame: 1 year
Testosterone and Luteinizing Hormone (LH) Recovery Rates
Testosterone and LH recovery rates will be measured at 8 months from the start of randomization and at each month of the 10 month follow up period.
Time frame: 8 -10 months
Correlative Tissue Analysis
Tissue samples will be utilized for morphologic assessment, percent tumor involvement (if applicable), and immunohistochemistry. The immunohistochemical markers assessed may be AR, PTEN, PSMA, fatty acid synthase (FASN), phospho-AMPK, phospho-ACC, phospho-S6 kinase, phospho-Akt for the assessment of the AMPK, lipid synthesis, mTOR pathways, and immunological markers.
Time frame: 1 year
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