Study of CP-675,206 in Bacillus Calmette-Guerin (BCG)-Resistant Bladder Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find out the highest safe dose of the investigational drug CP-675,206 when given in combination with BCG therapy to patients who have experienced recurrent superficial bladder cancer after standard BCG treatment. In addition, the study will look to see if taking CP 675,206 generates an immune response and evaluate how the drug affects superficial bladder cancer.

Official Title
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Phase I Dose-escalation Trial of CP-675,206 (Tremelimumab, Anti-CTLA-4 Monoclonal Antibody) for Patients With BCG-resistant Localized Transitional Cell Carcinoma of the Bladder

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: BCG and CP-675,206


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of transitional cell cancer of the bladder must have completed a transurethral resection of all visible bladder tumors, and have completed two previous 6-week courses with intravesical BCG. Evidence of disease recurrence within 1 year of previous BCG treatment Tumor tissue must be available from biopsy for study related immunohistochemical analysis If sexually active must use reliable form of contraception while on study and for 4 weeks after last treatment ECOG performance status of <2 Life expectancy of at least 6 months Adequate hematologic, renal and liver function Informed consent Exclusion Criteria: No evidence of immunosuppression or treated with immunosuppressive therapy within 6 months No prior radiation to the pelvis No gross hematuria within 1 week prior to planned week 1 treatment Cannot have previous intolerance to BCG Cannot be seropositive for HIV, hepatitis B(HBV) or hepatitis C(HCV) per patient history No evidence of metastatic disease No prior treatment with anti-CTLA-4 monoclonal antibody Can not be pregnant or lactating No history of autoimmune disorder No history of thyroid or adrenal insufficiency No history of inflammatory bowel conditions, including diverticulitis, ulcerative colitis, Crohn's or celiac disease, intractable urinary tract infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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>BCG 81 mg intravesical weekly x 6 beginning on week 1, and weekly x 3 beginning at week 15 in combination with CP-675,206 I.V. week 3, week 1 | Drug: BCG and CP-675,206<br>* Dose level -1: BCG 81 mg intravesical weekly x 6 beginning on week 1, and weekly x 3 beginning at week 15 CP-675,206 3 mg/kg I.V. week 3, week 15 Dose level 1: BCG 81 mg intravesical weekly x 6 beginning on week 1, and weekly x 3 beginning at week 15 CP-675,206 6 mg/kg I.V. week 3, week 15 Dose level 2: BCG 81 mg intravesical weekly x 6 beginning on week 1, and weekly x 3 beginning at week 15 CP-675,206 10 mg/kg IV week 3, week 15 Dose level 3: BCG 81 mg intravesical weekly x 6 beginning on week 1, and weekly x 3 beginning at week 15 CP-675,206 15 mg/kg IV week 3, week 15<br>* Other names: Tremelimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety of CP-675,206 when delivered in combination with BCG in patients with BCG-resistant bladder carcinoma in situ |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether patients treated with CP-675,206 in combination with BCG develop cancer antigen-specific systemic immune responses |  | 24 months | 
| To determine whether patients treated with CP-675,206 in combination with BCG develop an increase in tumor-infiltrating lymphocytes |  | 24 months | 
| To determine whether patients treated with CP-675,206 in combination with BCG develop pathological and cytological complete responses |  | 24 months | 
| To determine the 1-year recurrence-free survival |  | 24 months | 
| To determine a recommended dose and schedule for phase II trial evaluation based on the maximum tolerated dose |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bladder cancer, BCG-resistant localized transitional cell of the bladder