Clinical Trial: MEK162 in Combination With Capecitabine in Advanced Biliary Tract Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase Ib Study of MEK162 in Combination With Capecitabine in Gemcitabine-pretreated Advanced Biliary Tract Cancer

Brief Summary: This study is to test the efficacy of MEK162 plus capecitabine in gemcitabine-pretreated advanced biliary tract cancer, and to explore the predictive biomarkers for future large-scale clinical trials using this combination.

Detailed Summary:

Biliary tract cancer is one of rare cancers, which is relatively more frequent in east Asia. The frequency of KRAS mutation and/or BRAF mutation is reported at 40 to 60%. The prognosis is still very poor, with only limited treatment options. The most commonly used 1st-line chemotherapy is gemcitabine+cisplatin combination. In gemcitabine-pretreated advanced biliary tract cancer, fluoropyrimidine-based chemotherapy is used. However, the overall survival with these cytotoxic chemotherapies is still only about 8-10 months, calling for urgent development of efficient treatment options.

Recently, mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibition was shown to have antitumor effects in KRAS mutated biliary tract cancers in preclinical model. In phase II study of MEK inhibitor (selumetinib) in metastatic biliary tract cancers, selumetinib displayed interesting activity and acceptable tolerability.

MEK162 is an oral, highly selective MEK inhibitor. It was shown to promote apoptosis and in vivo antitumor activity against human biliary tract cancer cell lines. So far, there has been no study to test the MEK inhibitor mainly in gemcitabine-pretreated advanced biliary tract cancer, especially in combination of capecitabine chemotherapy.

The aim of this study is to test the efficacy of MEK162 plus capecitabine in gemcitabine-pretreated advanced biliary tract cancer, and to explore the predictive biomarkers for future large-scale clinical trials using this combination.


Sponsor: Seoul National University Hospital

Current Primary Outcome:

  • Maximum tolerated dose (MTD) [ Time Frame: 6 months ]
    MTD in all treated population (Phase 1 part)
  • Progression-free survival (PFS) [ Time Frame: 3 months ]
    PFS in all treated population (Expansion part)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Dose-limiting Toxicity (DLT) [ Time Frame: 6 months ]
    DLT in all treated population, according to NCI-CTCAE v 4.0 (Phase 1 part)
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: 6 months ]
    RP2D to be used at Expansion part (Phase 1 part)
  • Response rate [ Time Frame: 6 months ]
    Response rate in all treated patients (Expansion part)
  • Overall survival (OS) [ Time Frame: 1 year ]
    OS in all treated patients


Original Secondary Outcome:

  • Dose-limiting Toxicity [ Time Frame: 6 months ]
    DLT in all treated population, according to NCI-CTCAE v 4.0 (Phase 1 part)
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: 6 months ]
    RP2D to be used at Expansion part (Phase 1 part)
  • Response rate [ Time Frame: 6 months ]
    Response rate in all treated patients (Expansion part)
  • Overall survival (OS) [ Time Frame: 1 year ]
    OS in all treated patients


Information By: Seoul National University Hospital

Dates:
Date Received: May 13, 2016
Date Started: April 2016
Date Completion: December 2017
Last Updated: May 15, 2016
Last Verified: May 2016