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

Advanced Adult Hepatocellular Carcinoma Clinical Trial

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

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

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).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive trametinib orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive 1 of 2 treatment regimens at the discretion of the investigator.

ARM IIA: Patients receive leucovorin calcium intravenously (IV) over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM IIB: Patients receive capecitabine PO twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Cholangiocarcinoma
• Advanced Adult Hepatocellular Carcinoma
• BCLC Stage C Adult Hepatocellular Carcinoma
• BCLC Stage D Adult Hepatocellular Carcinoma
• Bile Duct Neoplasms
• Carcinoma
• Carcinoma, Ductal
• Carcinoma, Hepatocellular
• Cholangiocarcinoma
• Gallbladder Neoplasms
• Hilar Cholangiocarcinoma
• Klatskin Tumor
• Liver Neoplasms
• Localized Non-Resectable Adult Liver Carcinoma
• Recurrent Adult Liver Carcinoma
• Recurrent Childhood Liver Cancer
• Recurrent Extrahepatic Bile Duct Carcinoma
• Recurrent Gallbladder Carcinoma
• Stage II Gallbladder Cancer
• Stage III Childhood Hepatocellular Carcinoma
• Stage IIIA Gallbladder Cancer
• Stage IIIB Gallbladder Cancer
• Stage IV Childhood Hepatocellular Carcinoma
• Stage IV Distal Bile Duct Cancer
• Stage IVA Gallbladder Cancer
• Stage IVB Gallbladder Cancer
• Unresectable Extrahepatic Bile Duct Carcinoma

• NCT number: NCT02042443
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2014