Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer
To determine the activity of gemcitabine combined with carboplatin in the treatment of patients with metastatic or recurrent cholangiocarcinoma or gallbladder cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer|
- To determine the response rate and time to failure for patients treated with this regimen [ Time Frame: Every 3 cycles for a maximum of 9 cycles ] [ Designated as safety issue: No ]1 cycle = 21 days
- To describe the toxicities associated with gemcitabine and carboplatin in patients with cholangiocarcinoma or gallbladder cancer. [ Time Frame: 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
- To assess the clinical benefit, or lack thereof, of chemotherapy on patient's performance status and weight. [ Time Frame: At the end of study treatment ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: Every 3 months until progression ] [ Designated as safety issue: No ]
- Survival times [ Time Frame: Every 3 months until patient death ] [ Designated as safety issue: No ]
|Study Start Date:||March 2002|
|Study Completion Date:||April 2009|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
Experimental: Gemcitabine + Carboplatin
Gemcitabine 1000 mg/m2 IV for 30 minutes on days 1 and 8 of 21 day cycle. Maximum of 9 cycles.
Carboplatin AUC 5 IV for 1 hour on day 1 of 21 day cycle. Maximum of 9 cycles.
Other Name: GemzarDrug: Carboplatin
Due to better non-hematologic toxicity profile, less need for pre- and post chemotherapy hydration, and tolerability as compared to cisplatin, we propose to combine gemcitabine with carboplatin in the treatment of patients with cholangiocarcinoma and gallbladder carcinoma. In lung cancer, available literature suggests that carboplatin is as efficacious as cisplatin.
Several Phase I, II and III studies using gemcitabine with carboplatin have already been done or are currently ongoing. Phase I studies determined the maximum tolerated doses (MTD) of gemcitabine at 800-1250 mg/m2 days 1 and 8 combined with at AUC of 4-5.5, day 1 of a 21-day cycle.
Initial Phase II studies using a 28-day schedule using gemcitabine on days 1,8 and 15 with carboplatin caused severe thrombocytopenia on day 15 precluding day 15 treatment in over 50% of courses. A Spanish Lung Cancer Group conducted a sequential Phase II trial wherein 52% and 30% of the first 33 patients with lung cancer treated using the 28-day schedule were noted to have Grade 4 thrombocytopenia and neutropenia, respectively. Subsequently, the next 56 patients were treated on the 21-day schedule, and despite a higher dose intensity, response rates were equal (45-48%) with less Grade 4 thrombocytopenia (21%) but similar rates of Grade 4 neutropenia (27%).
A randomized Italian Phase II studies have demonstrated that when gemcitabine was given at doses of 1 g/m2 with carboplatin at AUC of 5 mg/mL/min were tolerable and when compared to gemcitabine and cisplatin caused less non-hematologic toxicities. Current Phase III trials in lung cancer utilizes the 21-day schedule with gemcitabine at 1000 mg/m2 on days 1 and 8 and carboplatin at AUC of 5.5.
Therefore, our proposed schedule will be gemcitabine at 1000 mg/m2 IV over 30 minutes on days 1 and 8 with carboplatin dosed at an AUC of 5 on day 1 of a 21-day cycle.
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Benjamin Tan, M.D.||Washington University School of Medicine|