A Safety and Tolerability Study of SCH 721015 in Patients With Transitional Cell Carcinoma of the Bladder (Study P03816)

Phase 1

Completed

• Conditions: Bladder Neoplasms
• Interventions: Genetic: SCH 721015 with SCH 209702

• Registration Number: NCT00536588
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this first-in-human study is to determine the safety and tolerability of SCH 721015 in subjects with transitional cell carcinoma of the bladder.

Detailed Description

A nonrandomized, open-label, rising-dose, parallel-group, multi-center study of SCH 721015 in patients with papillary bladder cancer, or carcinoma in situ that is refractory to Bacillus Calmette-Guerin. Subjects will receive a single intravesical administration of SCH 721015 with SCH 209702 in a total volume of 75 mL with a 1-hour dwell time. Subjects who at 3 months post administration demonstrate a complete response (CR on cystoscopy/biopsy and cytology) and who did not experience dose-limiting toxicity will be allowed to receive a second intravesical administration at the same dose level.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2007-09-26
• Study First Submitted QC: 2007-09-26
• Study First Posted: 2007-09-28
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-26
• Last Update Posted: 2015-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Histologically proven recurrent transitional cell carcinoma of the bladder, Stage Tis, Ta.
• Patients with recurrent T1 disease who do not wish to have cystectomy.
• Subjects must have failed at least two prior courses of BCG with or without recombinant interferon alpha administration.
• At least 3 months must have passed since last intravesical treatment for bladder carcinoma.
• Subjects must be 18 years of age or older.
• Life expectancy of at least 3 months.
• Adequate performance status (Karnofsky score >=70%).
• Adequate laboratory values.

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Exclusion Criteria

• Suspected hypersensitivity to interferon alpha.

• Subjects with organ transplants.

• Any known preexisting medical condition that could interfere with the subject's participation in and completion of the study such as:

  • History of psychosis or presence of poorly controlled depression;
  • CNS trauma or active seizure disorders requiring medication;
  • Significant cardiovascular dysfunction within the past 6 months including symptomatic cardiac ischemia, arrhythmia or congestive heart failure requiring hospitalization or emergency room visit within last 3 months;
  • Poorly controlled diabetes mellitus (HbA1C >10.0%);
  • Unstable chronic pulmonary disease requiring hospitalization or emergency room visit within the last 3 months;
  • Immunologically mediated disease (eg, rheumatoid arthritis, autoimmune hepatitis, immune mediated glomerulonephritis).

• History of any clinically significant local or systemic infectious disease within 4 weeks prior to initial treatment administration.

• Untreated bladder infection.

• Positive for hepatitis BsAg or HIV Ab or hepatitis C.

• Immunosuppressive therapy within the last 3 months.

• BCG therapy or intravesical therapy within 3 months.

• Traumatic catheterization within 1 month.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SCH 721015 with SCH 209702	SCH 721015 with SCH 209702	-

Primary Outcome Measures

Name	Time	Method
Adverse events, laboratory safety tests, dose-limiting toxicity	ECG and VS - predose and selected postdose time points.

Secondary Outcome Measures

Name	Time	Method
Timed urine collections for IFNα2b excretion & IP-10.	Days 1-7, 10, 14, 21, & 28/29.
Urine samples for SCH 721015 DNA content.	Predose, Days 1-7 & 14.
Blood samples for SCH 721015 DNA; SCH 209702, & IFNα2b levels; antiadenoviral & anti-IFNα2b antibodies	Pre- & postdose for SCH 721015 DNA; SCH 721015, & IFNα2b levels; & postdose for antibodies.
Urine cytology & FISH	Days 1, 30 & 90
Cystoscopy & bladder biopsies	Screening & Day 90