Trial of Combination ABI-007, Carboplatin, and Gemcitabine for First Line Treatment of Advanced Urothelial Cancer
This study will evaluate the safety and efficacy of the combination of ABI-007, carboplatin and gemcitabine in the treatment of patients with advanced bladder cancer.
Study participants will have been diagnosed with advanced bladder cancer. Cisplatin based chemotherapy in this setting has activity but is not curative. Furthermore, patients with this disease have comorbidities that limit the use of cisplatin based therapy. Combination paclitaxel, carboplatin and gemcitabine is active and well tolerated in this patient population.
Paclitaxel is formulated with ethanol and a Cremophor EL (polyoxyethylated castor oil) which contribute to the side effects associated with paclitaxel. ABI-007 (brand name Abraxane™) is a form of paclitaxel that does not contain these additives and may deliver more drug to tumor cells. ABI-007 is approved by the United States Food and Drug Administration (FDA) in the treatment of metastatic (advanced) breast cancer based on superior anticancer effect, and is being evaluated in other cancers in research studies.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||ABX209: Phase II Trial of Combination ABI-007, Carboplatin, and Gemcitabine for First Line Treatment of Advanced Urothelial Cancer.|
- Clinical efficacy of ABI-007 based therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Safety and clinical outcomes [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
ABI-007 combined with Carboplatin, and Gemcitabine
Drug: ABI-007 (Abraxane®)
ABI-007 is a novel albumin-bound paclitaxel combining a protein with a chemotherapeutic agent in the particle form.
On the basis of the known single agent activity of paclitaxel in urothelial cancer, the activity of combination therapy with paclitaxel, carboplatin, and gemcitabine in advanced urothelial cancer coupled with the results from studies in breast cancer demonstrating improved clinical efficacy of ABI-007 over paclitaxel with a more favorable toxicity profile, we propose this phase II trial evaluating the efficacy and safety of the combination of ABI-007, carboplatin, and gemcitabine in patients with advanced urothelial cancer.
Carboplatin and gemcitabine dosing and schedule is based on our previous trial of paclitaxel, carboplatin, and gemcitabine which showed acceptable toxicity.
Due to the extent of hematologic toxicities expected with this combination and reported with weekly schedules of ABI-007 based combinations as well as our experience on UMCC protocol 2007.061 which originally utilized a weekly ABI-007 with gemcitabine and carboplatin, we do not feel continuous weekly dosing will be feasible. Therefore this trial is designed with ABI-007 on a D1 only schedule every 21 days. The starting dose of ABI-007 will be 220 mg/m2, because of the risk of significant bone marrow suppression, with the option of a dose escalation in patients who tolerate therapy well after the first cycle to 260 mg/m2 every 21 days.
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Maha Hussain, MD||University of Michigan Medical School/Internal Medicine Dept.|