Trial Information

A Phase II Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer

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.