Bladder Neoplasms
Conditions
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.
Interventions
GENETICSCH 721015 with SCH 209702
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).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events, laboratory safety tests, dose-limiting toxicity | CBC/chemistry: predose, Days 1-3, 7, 14, 21, & 28, Week 12. |
Secondary
| Measure | Time frame |
|---|---|
| Urine cytology & FISH | Days 1, 30 & 90 |
| 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. |
| Cystoscopy & bladder biopsies | Screening & Day 90 |
Outcome results
None listed