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

Bladder Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536588
• Other study ID #: P03816
• Status: Completed
• Phase: Phase 1
• First received: September 26, 2007
• Last updated: March 26, 2015
• Start date: September 2006
• Est. completion date: August 2009

Study information

• Verified date: March 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Neoplasms
• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms

Intervention

Genetic:
• SCH 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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Dinney CP, Fisher MB, Navai N, O'Donnell MA, Cutler D, Abraham A, Young S, Hutchins B, Caceres M, Kishnani N, Sode G, Cullen C, Zhang G, Grossman HB, Kamat AM, Gonzales M, Kincaid M, Ainslie N, Maneval DC, Wszolek MF, Benedict WF. Phase I trial of intrave — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events, laboratory safety tests, dose-limiting toxicity		CBC/chemistry: predose, Days 1-3, 7, 14, 21, & 28, Week 12.	Yes
Primary	Adverse events, laboratory safety tests, dose-limiting toxicity		Additional hematology on Days 4, 5, & 6.	Yes
Primary	Adverse events, laboratory safety tests, dose-limiting toxicity		AEs: Duration of study; up to 3 years postdose for serious events.	Yes
Primary	Adverse events, laboratory safety tests, dose-limiting toxicity		ECG and VS - predose and selected postdose time points.	Yes
Secondary	Timed urine collections for IFNa2b excretion & IP-10.		Days 1-7, 10, 14, 21, & 28/29.	No
Secondary	Urine samples for SCH 721015 DNA content.		Predose, Days 1-7 & 14.	No
Secondary	Blood samples for SCH 721015 DNA; SCH 209702, & IFNa2b levels; antiadenoviral & anti-IFNa2b antibodies		Pre- & postdose for SCH 721015 DNA; SCH 721015, & IFNa2b levels; & postdose for antibodies.	No
Secondary	Urine cytology & FISH		Days 1, 30 & 90	No
Secondary	Cystoscopy & bladder biopsies		Screening & Day 90	No