CP-675,206 in Combination With Short Term Androgen Deprivation in Patients With Stage D0 Prostate Cancer

Phase 1

Terminated

Interventions: Drug: Bicalutamide and CP-675,206 (Tremelimumab)
Drug: Bicalutamide, CP-675,206 (Tremelimumab)
Drug: Bicalutamide, CP-675,206

Brief Summary: The current protocol will evaluate the safety of combining treatment with bicalutamide(Casodex) and CP-675,206 (anti-CTLA-4 monoclonal antibody) in patients with PSA-recurrent non-metastatic (stage D0) prostate cancer. This is a dose escalation study with safety the primary endpoint. Secondary endpoints will be to determine whether prostate associated immune responses are seen, and whether treatment is associated with an increase in PSA doubling time and PSA recurrence at one year, as markers of clinical activity. Cohorts of six patients will be treated in each dose level. The investigators hypothesize that short-term androgen deprivation therapy will elicit prostate cancer-associated T-cell mediated tissue destruction that can be augmented with a monoclonal antibody blocking CTLA-4, and that this will have therapeutic benefit in patients with recurrent prostate cancer.

Detailed Description: This is an open label, single-center Phase I study. All subjects will receive bicalutamide 150mg orally days 1-28. Subjects will receive CP-675,206 IV over one hour on day 29. Doses will range from 6 mg/kg to 15 mg/kg. This cycle will be repeated once at month 3. Once the maximum tolerated dose has been determined, up to 6 additional subjects will be enrolled.

Recruitment & Eligibility

Inclusion Criteria

At least 18 years of age & histologic diagnosis of adenocarcinoma of the prostate
Completed surgery or radiation at least 8 weeks prior to entry with removal of all visible disease
Clinical Stage D0 prostate cancer with rising PSA and PSA >2ng/ml.
ECOG performance of <2
Normal hematologic, renal and liver function

Exclusion Criteria

Cannot have evidence of immunosuppression or have been treated with immunosuppressive therapy.
No prior treatment with an LHRH agonist or nonsteroidal antiandrogen such as casodex or flutamide
No evidence for metastatic disease per bone scan or CT scan of the abdomen and pelvis
No prior treatment with anti-CTLA 4 monoclonal antibody
No history of known autoimmune disorder or HIV, hepatitis B or hepatitis C
No known brain metastases
No history of inflammatory bowel conditions including diverticulitis, ulcerative colitis, etc.

Arm && Interventions

Group	Intervention	Description
1	Bicalutamide and CP-675,206 (Tremelimumab)	Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3
1	Bicalutamide, CP-675,206 (Tremelimumab)	Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3
1	Bicalutamide, CP-675,206	Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3

Primary Outcome Measures

Name	Time	Method
The Number of Participants Who Developed Cancer Antigen-specific Immune Responses	Up to 12 months after treatment with study agent

Secondary Outcome Measures

Name	Time	Method
The Number of Participants With an Increase in PSA Doubling Time	Up to 18 months after last dose of study agent
Number of Participants With PSA Recurrence.	one year	PSA recurrence is defined as a minimum PSA value of greater or equal to 1.0ng/ml occurring within one year after the last treatment with CP-675,206, with a confirmatory PSA blood teat performed at least 2 weeks later.