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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: BCG and CP-675,206

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; 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; 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; Other Names: Tremelimumab; Bacille Calmette-Guerin (BCG)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Pfizer
• Investigators: Principal Investigator: Douglas G McNeel, M.D., Ph.D., University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: April 13, 2009
• First Submitted That Met QC Criteria: April 13, 2009
• First Posted (Estimate): April 14, 2009

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: bladder cancer; BCG-resistant localized transitional cell of the bladder
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Antineoplastic Agents; Tremelimumab
• Other Study ID Numbers: CO08807; A534260 (Other Identifier: UW Madison); SMPH/MEDICINE/MEDICINE*H (Other Identifier: UW Madison); NCI-2011-03676 (Registry Identifier: NCI Trial ID); H-2008-0227 (Other Identifier: Institutional Review Board)