3-arm Study of Abiraterone Acetate Alone, Abiraterone Acetate Plus Degarelix, a GnRH Antagonist, and Degarelix Alone for Patients With Prostate Cancer With a Rising PSA or a Rising PSA and Nodal Disease Following Definitive Radical Prostatectomy
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.
Drug: Abiraterone acetate
Drug: Abiraterone acetate plus degarelix
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2, Randomized, 3-arm Study of Abiraterone Acetate Alone, Abiraterone Acetate Plus Degarelix, a GnRH Antagonist, and Degarelix Alone for Patients With Prostate Cancer With a Rising PSA or a Rising PSA and Nodal Disease Following Definitive Radical Prostatectomy|
- progression-free survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]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 randomization.
- Soft tissue complete response [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- PSA response rate [ Time Frame: 8 months ] [ Designated as safety issue: No ]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.
- overall quality of life [ Time Frame: 1 year ] [ Designated as safety issue: No ]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,
- non-hematologic adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]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.
- Testosterone and luteinizing hormone (LH) recovery rates [ Time Frame: 8 -10 months ] [ Designated as safety issue: No ]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.
- Correlative tissue analysis [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||October 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Abiraterone acetate
Drug: Abiraterone acetate
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.
Experimental: Abiraterone acetate and Degarelix
Abiraterone acetate 1000 mg daily x 8 months
Drug: Abiraterone acetate plus degarelix
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 single 80 mg subcutaneous injections (maintenance doses) every 28 days (±3 days) thereafter.
• Degarelix subcutaneous depot injection q 1 month x 8 months
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 single 80 mg subcutaneous injections (maintenance doses) every 28 days (± 3 days) thereafter.
|Contact: Howard I Scher, MD||646-422-4330|
|Contact: Michael Morris, MD||646-422-4469|
|United States, Illinois|
|Northwestern University, Feinberg School of Medicine||Not yet recruiting|
|Chicago, Illinois, United States, 60611|
|Principal Investigator: Timothy Kuzel, MD|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Not yet recruiting|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator: Emmanuel Antonarakis, MD|
|United States, Michigan|
|Karmanos Cancer Institute, Wayne State University||Not yet recruiting|
|Detroit, Michigan, United States, 48201|
|Principal Investigator: Ulka Vaishampayan, MD|
|United States, New Jersey|
|Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator: Tina Mayer, MD|
|United States, New York|
|NorthShore University Health System||Recruiting|
|Long Island, New York, United States|
|Principal Investigator: Daniel Shevrin, MD|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Howard I. Scher, MD 646-422-4330|
|Contact: Michael Morris, MD 646-422-4469|
|Principal Investigator: Howard I Scher, MD|
|United States, North Carolina|
|University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27514|
|Principal Investigator: Matthew Milowsky, MD|
|Duke University Medical Center||Not yet recruiting|
|Durham, North Carolina, United States, 27701|
|Principal Investigator: Michael Harrison, MD|
|United States, Oregon|
|Oregon Health & Science University Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Julie Graff, MD|
|Principal Investigator: Julie Graff, MD|
|Principal Investigator:||Howard I Scher, MD||Memorial Sloan-Kettering Cancer Center|