Clinical Trial: Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized Phase II Trial of Single Agent MEK Inhibitor Trametinib (GSK1120212) Vs 5-Fluorouracil or Capecitabine in Refractory Advanced Biliary Cancer

Brief Summary: This randomized phase II trial studies how well trametinib or combination chemotherapy works in treating patients with refractory or advanced biliary or gallbladder cancer or that cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving trametinib is more effective than combination chemotherapy in treating patients with biliary or gallbladder cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess overall survival (OS) in patients with refractory advanced biliary cancer randomized to Arm 1: trametinib compared to those randomized to Arm 2: chemotherapy (either 5-fluorouracil [fluorouracil] and leucovorin [leucovorin calcium] or capecitabine).

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events of trametinib in this patient population.

II. To assess response rate (RR) and progression-free survival (PFS) in patients randomized to Arm 1: trametinib and patients randomized to Arm 2: chemotherapy (fluorouracil [5-FU] or capecitabine in this patient population).

TERTIARY OBJECTIVES:

I. To determine if a 16-gene expression signature is predictive of mitogen-activated protein kinase kinase (MEK) efficacy as evidenced by improved RR, PFS, and OS.

II. To evaluate the effects of trametinib on the inflammatory cytokine and explore potential associations with response rate and survival.

III. To estimate lean soft tissue and fat mass weight gain as a result of treatment with trametinib vs. capecitabine in patients with advanced refractory biliary cancer.

IV. To bank tissue samples for other future correlative studies including next generation sequencing and whole genome methylation assays. NOTE: These potential future correlative studies will not be performed until an amended protocol with relevant detailed information including specific arms and assays is approved by Cancer Therapy Evaluation Program (CTEP).

The final analysis will be based on a stratified log rank test.