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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Dose Escalation Trial of CP-675,206 (Tremelimumab, Anti-CTLA-4 Monoclonal Antibody) in Combination With Short Term Androgen Deprivation in Patients With Stage D0 Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Bicalutamide and CP-675,206 (Tremelimumab)
* Drug: Bicalutamide, CP-675,206 (tremelimumab)
* Drug: Bicalutamide, CP-675,206 (Tremelimumab)
* Drug: Bicalutamide, CP-675,206 (Tremelimumab)
* Drug: Bicalutamide, CP-675,206


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3 | Drug: Bicalutamide and CP-675,206 (Tremelimumab)<br>* Dose level -1 : Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 3 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)<br>* Other names: Tremelimumab;Drug: Bicalutamide, CP-675,206 (tremelimumab)<br>* Dose level 1: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 6 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)<br>* Other names: Tremelimumab;Drug: Bicalutamide, CP-675,206 (Tremelimumab)<br>* Dose level 2: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 10 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)<br>* Other names: Tremelimumab;Drug: Bicalutamide, CP-675,206 (Tremelimumab)<br>* Dose level 3: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 15 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)<br>* Other names: Tremelimumab;Drug: Bicalutamide, CP-675,206<br>* Final Dose Level: Bicalutamide 150 mg p.o. q.d. day 1-28, day 85-112 At month 9, if evidence of PSA progression: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 (MTD dose) I.V. over 1 hour, day 29<br>* Other names: Tremelimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Developed Cancer Antigen-specific Immune Responses |  | Up to 12 months after treatment with study agent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage D0 Prostate Cancer, Rising PSA, Casodex, Tremelimumab