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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00536588
First received: September 26, 2007
Last updated: April 18, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Bladder Neoplasms
Genetic: SCH 721015 with SCH 209702
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

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

Secondary Outcome Measures:
  • Timed urine collections for IFNα2b excretion & IP-10. [ Time Frame: Days 1-7, 10, 14, 21, & 28/29. ] [ Designated as safety issue: No ]
  • Urine samples for SCH 721015 DNA content. [ Time Frame: Predose, Days 1-7 & 14. ] [ Designated as safety issue: No ]
  • Blood samples for SCH 721015 DNA; SCH 209702, & IFNα2b levels; antiadenoviral & anti-IFNα2b antibodies [ Time Frame: Pre- & postdose for SCH 721015 DNA; SCH 721015, & IFNα2b levels; & postdose for antibodies. ] [ Designated as safety issue: No ]
  • Urine cytology & FISH [ Time Frame: Days 1, 30 & 90 ] [ Designated as safety issue: No ]
  • Cystoscopy & bladder biopsies [ Time Frame: Screening & Day 90 ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: September 2006
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SCH 721015 with SCH 209702 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).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00536588     History of Changes
Other Study ID Numbers: P03816
Study First Received: September 26, 2007
Last Updated: April 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 20, 2014