A Randomized, Double-blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination With OGX-427 or Placebo in Patients With Advanced Transitional Cell Carcinoma
The incidence of bladder cancer in 2010 in the US and Canada combined is estimated to be
77,680, with 16,520 deaths and in Europe in 2008 was 110,500 with 38,200 deaths. The most
common histological type is transitional cell cancer (TCC). Most cases (70%) present with
superficial or non-invasive disease which, in general, has a good prognosis. However, at
diagnosis, 20% of patients will have advanced disease (muscular invasion) and 5% will
present with metastatic disease. In addition, 50-70% of superficial tumors will recur and a
significant proportion will evolve to muscular involvement within 5 years. Radical
cystectomy is the treatment of choice for patients with operable invasive disease. Patients
who present with locally inoperable disease due to local extension into organs other than
the bladder or involvement of regional lymph nodes do not have this option, and, despite
radical cystectomy, 50% of patients will recur either regionally (~30%) or systemically
(~70%) following cystectomy. Following recurrence, few patients can be cured.
Before the advent of chemotherapy, survival of patients with metastatic TCC was <6 months.
Today, TCC is felt to be a chemotherapy sensitive disease, and systemic chemotherapy is the
treatment of choice for patients with inoperable, locally advanced, or metastatic disease.
This study evaluates the safety and efficacy of the standard chemotherapy (gemcitabine and
cisplatin) in combination with OGX-427 at two dose levels (600 mg and 1000 mg) or placebo in
patients with advanced TCC who have not previously received chemotherapy for metastatic
disease and are not candidates for potential curative surgery or radiotherapy.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
To determine whether there is evidence of longer survival relative to the control arm for three comparisons: 600 mg OGX-427; 1000 mg OGX-427; and pooled 600 mg and 1000 mg OGX-427 arms. OS is defined as the time from randomization to death from any cause; OS will be censored on date of last contact for patients still alive at time of analysis.
From date of randomization to date of death from any cause (approx 12 months)
Daniel Petrylak, MD
United States: Food and Drug Administration
|Cedars-Sinai Medical Center||Los Angeles, California 90048|
|Texas Oncology, P.A.||Dallas, Texas 75246|
|City of Hope National Medical Center||Los Angeles, California 91010|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|
|University of California Los Angeles||Los Angeles, California 90095-6951|
|Yale University||New Haven, Connecticut 06520|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|Karmanos Cancer Institute||Detroit, Michigan 48201|
|Columbia University Medical Center||New York, New York 10032|
|Radiological Associates of Sacramento||Sacramento, California 95816|
|Monter Cancer Center||Lake Success, New York 11042|
|Siteman Cancer Center, Washington University School of Medicine||St. Louis, Missouri|
|Urology Cancer Center and GU Research Network||Omaha, Nebraska|
|Montefiore Medical Center, Albert Einstein College of Medicine||Bronx, New York|