Gemcitabine and Sorafenib in Advanced Biliary Tract Cancer (GEMSO)
Summary
This trial will be conducted to evaluate the efficacy, safety and tolerability of a combination of gemcitabine plus sorafenib in comparison of gemcitabine plus placebo as a first-line palliative therapy in chemo-naive advanced or metastatic CCC. There is strong scientific rationale for exploring the role of sorafenib in combination with gemcitabine in advanced CCC. Sorafenib is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGF-R2, R3 and PDGFR-β. Mutations in these signaling pathways display by far the most common genetic alterations in CCC and overexpression correlates to poor prognosis. Furthermore, there is no evidence of a consistent or meaningful pharmacokinetic interaction between sorafenib and gemcitabine, suggesting that sorafenib can safely be combined with gemcitabine. Clinical results of a combination of sorafenib and gemcitabine in a phase I study in pancreatic cancer suggested a therapeutic effect, and the safety and efficacy results together with the knowledge of the molecular pathology of CCC provide a rationale for a randomized, placebo-controlled phase II trial consisting of gemcitabine plus sorafenib in advanced CCC.
Timeline
- Start
- 2008-05
- Primary completion
- 2010-06
- Completion
- 2010-06
Outcome
Missed primary endpoint
registry MEDIAN Gemcitabine + Sorafenib: 91 (54 to 218) days MEDIAN Gemcitabine + Placebo: 148 (105 to 233) days NCT00661830 ↗
registry Hazard Ratio (HR) 1.281 (95% CI 0.811 to 2.023); Regression, Cox NCT00661830 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Sorafenib | Small molecule | 400 mg | Oral |
| Background | Gemcitabine | Small molecule | 1000 mg/m2 | Intravenous |