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

Study Overview
=================
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.

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

Conditions
-----------------
Bladder Neoplasms

Intervention / Treatment
-----------------
* Genetic: SCH 721015 with SCH 209702


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCH 721015 with SCH 209702<br> | Genetic: SCH 721015 with SCH 209702<br>* Each subject receives a single intravesical administration of SCH 721015 with SCH 209702 at dose levels of 1 x 10^9 to 3 x 10^11 particles/mL (based on assessment of tolerability, intermediate dose levels may be used).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, laboratory safety tests, dose-limiting toxicity |  | CBC/chemistry: predose, Days 1-3, 7, 14, 21, & 28, Week 12. | 
| Adverse events, laboratory safety tests, dose-limiting toxicity |  | Additional hematology on Days 4, 5, & 6. | 
| Adverse events, laboratory safety tests, dose-limiting toxicity |  | AEs: Duration of study; up to 3 years postdose for serious events. | 
| Adverse events, laboratory safety tests, dose-limiting toxicity |  | ECG and VS - predose and selected postdose time points. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |