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
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Abiraterone acetate; Abiraterone acetate plus degarelix; Degarelix
Intervention description: 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.
Intervention MeSH terms: Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ABIRATERONE ACETATE (CB 7630); DEGARELIX; PREDNISONE; 12-187

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.
    

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