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

NCT ID: NCT01751451

Last Updated: 2021-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-18
• Study Completion Date: 2020-09-28

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

ABIRATERONE ACETATE (CB 7630); DEGARELIX; PREDNISONE; 12-187

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Abiraterone acetate

Group 1

• Abiraterone acetate 1000 mg daily x 8 months
• Prednisone 5 mg once daily x 8 months

Group Type: EXPERIMENTAL

Abiraterone acetate

Intervention Type: DRUG

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.

Abiraterone acetate and Degarelix

Group 2

Abiraterone acetate 1000 mg daily x 8 months

• Prednisone 5 mg once daily x 8 months
• Degarelix subcutaneous depot injection q 1 month x 8 months

Group Type: EXPERIMENTAL

Abiraterone acetate plus degarelix

Intervention Type: DRUG

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.

Degarelix

Group 3

• Degarelix subcutaneous depot injection q 1 month x 8 months

Group Type: EXPERIMENTAL

Degarelix

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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 80 mg subcutaneous doses (maintenance doses) every 28 days (±3 days) thereafter.

Intervention Type: DRUG

Degarelix

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization) NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Male aged 18 years and above
• Patients must have undergone local treatment via radical prostatectomy
• Patients who have received primary radiation therapy followed by a salvage radical prostatectomy are eligible.
• Patients who have had post-operative radiation therapy for presumed locally recurrent disease are eligible
• Histologically confirmed prostate cancer (per standards at Institution of participant registration) currently with progressive disease, defined as:
• Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 week apart). The 50% rise in PSA is across the 3 determinations, and these determinations do not need to be sequential AND
• PSADT ≤ 9 months as calculated according to the Memorial Sloan-Kettering Cancer Center nomogram (http://www.mskcc.org/mskcc/html/10088.cfm) OR
• Rising PSA as defined above AND
• Metastatic disease limited to the presence of pelvic and/or retroperitoneal nodes < 2 cm in short axis.
• Patients must have a serum testosterone of 150 ng/dL or greater
• ECOG performance status of ≤ 2 (Appendix A)
• Adequate bone marrow, hepatic, and renal function, as evidenced within 14 days prior to treatment initiation by:
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL without need for hematopoietic growth factor or transfusion support within 30 days prior to treatment initiation
• Aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of the normal range (x ULN)
• Alanine aminotransferase (ALT) ≤ 1.5 x ULN
• Total bilirubin ≤ 1.5 x ULN
• Serum creatinine of ≤ 1.5 mg/dl or Calculated creatinine clearance of ≥ 60 mL/min
• Serum albumin ≥ 3.0 g/dL
• Serum potassium ≥ 3.5 mEq/L
• Prothrombin time (PT) ≤ 1.5 x ULN (or international normalized ratio [INR] ≤ 1.3) unless the patient is receiving anticoagulant therapy
• Partial thromboplastin time (PTT) ≤ 1.5 x ULN unless the patient is receiving anticoagulant therapy At least 4 weeks and recovery to Grade 0-1 from reversible effects of prior surgery (i.e., incisional pain, wound drainage)
• Able to swallow the study drug whole as a tablet
• Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
• Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the study and for 1 week after last dose of abiraterone acetate.

Exclusion Criteria

• Prior cytotoxic chemotherapy or biologic therapy for prostate cancer
• More than 8 months of prior hormonal therapy (e.g., gonadotropin-releasing hormone analogs, megestrol acetate, or Casodex) Note: Patients who have been on prior hormonal therapy must wait at least 1 year after the drug is fully metabolized to start treatment on protocol.
• Prior ketoconazole, abiraterone acetate, or enzalutamide for the treatment of prostate cancer.
• Known brain metastasis or evidence of metastatic disease by CT scan, physical exam, or bone scan within 4 weeks of registration
• Patients with equivocal uptake on a bone scan that in the clinician's opinion do not definitively constitute metastatic disease are eligible
• Currently active second malignancy

Significant medical condition other than cancer, that would prevent consistent and compliant participation in the study that would, in the opinion of the investigator, make this protocol unreasonably hazardous including but not limited to:

• Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Severe hepatic impairment (Child-Pugh Class C)
• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
• Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
• Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
• Uncontrolled diabetes mellitus
• Active psychiatric condition Use of any prohibited concomitant medications (Section 5.5) within 30 days prior to Cycle 1, Day 1
• Pre-existing condition that warrants long-term corticosteroid use in excess of study dose
• Grade > 2 treatment-related toxicity from prior therapy
• Known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisone or degarelix
• Administration of an investigational therapeutic within 30 days of Cycle 1, Day1
• Any condition which, in the opinion of the investigator, would preclude participation in this trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: collaborator

Rutgers Cancer Institute of New Jersey

OTHER

Sponsor Role: collaborator

Endeavor Health

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

Northwestern University Feinberg School of Medicine

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: collaborator

University of North Carolina

OTHER

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: collaborator

Perlmutter New York University Cancer Center

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

Ferring Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

GU Research Network, LLC

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Howard I Scher, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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

Weill Cornell Medical Center

New York, New York, United States

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

12-187

Identifier Type: -

Identifier Source: org_study_id