Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery (S1310)
|Adult Cholangiocarcinoma Advanced Adult Hepatocellular Carcinoma BCLC Stage C Adult Hepatocellular Carcinoma BCLC Stage D Adult Hepatocellular Carcinoma Hilar Cholangiocarcinoma 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||Drug: Capecitabine Drug: Fluorouracil Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Trametinib||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Randomized Phase II Trial of Single Agent MEK Inhibitor Trametinib (GSK1120212) Vs 5-Fluorouracil or Capecitabine in Refractory Advanced Biliary Cancer|
- Overall Survival [ Time Frame: Up to 2 years from registration ]From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Up to 2 years ]Only adverse events that are possibly, probably or definitely related to study drug are reported.
- Objective Response Rate [ Time Frame: Up to 2 years from registration ]Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
- Progression-free Survival [ Time Frame: Up to 2 years from registration ]From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
|Study Start Date:||February 2014|
|Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Trametinib
Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15 (courses repeat every 28 days); or B) capecitabine PO BID on days 1-14 (courses repeat every 21 days). Patients treated until disease progression or unacceptable toxicity.
Other Names:Drug: Fluorouracil
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Leucovorin Calcium
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).
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).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02042443
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|Principal Investigator:||Richard Kim||Southwest Oncology Group|