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

A Phase 1 Study of the Safety and Tolerability of Intravesical Administration of SCH 721015 in Patients With Transitional Cell Carcinoma of the Bladder

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.

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.

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.

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.