CP-675,206 With Neoadjuvant Hormone Therapy in Patients With High Risk Prostate Cancer

A Phase 1, Open Label, Non-Randomized, Dose Escalation Study to Evaluate the Safety of CP-675,206 in Combination With Neoadjuvant Androgen Ablation and a Phase 2, Open Label, Randomized Study to Evaluate the Efficacy of CP-675,206 in Combination With Neoadjuvant Androgen Ablation and Androgen Ablation Alone in Patients With High Risk Prostate Cancer

This is a multi-center, open label, randomized study. Patients will be randomized to one of the following arms with an allocation ratio of 3:1, respectively: Arm A: CP-675,206 + neoadjuvant hormone therapy (NHT) OR Arm B: neoadjuvant hormone therapy. After randomization, patients will receive study treatment for three cycles (one cycle is defined as 28 days). After completion of three cycles, patients will undergo a prostatectomy and pathology assessments will be completed at a central laboratory, the Armed Forces Institute of Pathology (AFIP) in Washington, DC.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate, previously untreated
• Potential candidate for radical prostatectomy on the basis of the patient's general medical condition, performance status, and life expectancy
• Potential candidate for NHT prior to prostatectomy, including high or intermediate risk of recurrence, based on an estimated risk of biochemical recurrence: High risk category: PSA >20 or Gleason score 8 or cT2c/cT3 OR Intermediate risk category: PSA >10 and d20 or Gleason score 7 or cT2b
• No evidence of metastatic disease by physical examination, bone scan, and computed tomography, or MRI, of the abdomen and pelvis
• Age > 18 years
• ECOG performance status 0-1
• Adequate bone marrow, hepatic, and renal function determined within 2 weeks prior to starting therapy
• Availability of prostatectomy specimen for histological analysis at the Armed Forces Institute of Pathology

Exclusion Criteria:

• Prior hormone therapy, radiation, chemotherapy, or immunologic therapy for prostate cancer
• History of, or significant risk for, chronic inflammatory or autoimmune disease
• Potential requirement for systemic corticosteroids before surgery based on prior history
• History of autoimmune colitis or chronic GI conditions associated with diarrhea or bleeding, or current acute colitis of any origin
• Any serious uncontrolled medical disorder or active infection which would impair ability to receive study treatment and subsequent prostatectomy
• Coexisting malignancies except basal or squamous cell carcinoma of the skin