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MEK162 in Combination With Capecitabine in Advanced Biliary Tract Cancer

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ClinicalTrials.gov Identifier: NCT02773459
Recruitment Status : Completed
First Posted : May 16, 2016
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Seoul National University Hospital

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.

Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Drug: MEK162+capecitabine Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study of MEK162 in Combination With Capecitabine in Gemcitabine-pretreated Advanced Biliary Tract Cancer
Study Start Date : April 2016
Actual Primary Completion Date : January 7, 2019
Actual Study Completion Date : January 7, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 part
to assess the maximal tolerated dose (MTD) of MEK162+Capecitabine combination
Drug: MEK162+capecitabine
In phase 1 part: capecitabine(mg/m2) will be given twice a day, 2 week on/1week off Q 3weeks + MEK162 twice a day, continuously, starting at 1000mg/m2 and 30mg/m2 respectively. Expansion part will be treated with the dose found at phase 1 part.
Other Name: MEK162, xeloda

Experimental: Expansion part
to assess the efficacy (PFS) of MEK162+Capecitabine combination
Drug: MEK162+capecitabine
In phase 1 part: capecitabine(mg/m2) will be given twice a day, 2 week on/1week off Q 3weeks + MEK162 twice a day, continuously, starting at 1000mg/m2 and 30mg/m2 respectively. Expansion part will be treated with the dose found at phase 1 part.
Other Name: MEK162, xeloda




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 6 months ]
    MTD in all treated population (Phase 1 part)

  2. Progression-free survival (PFS) [ Time Frame: 3 months ]
    PFS in all treated population (Expansion part)


Secondary Outcome Measures :
  1. Dose-limiting Toxicity (DLT) [ Time Frame: 6 months ]
    DLT in all treated population, according to NCI-CTCAE v 4.0 (Phase 1 part)

  2. Recommended Phase 2 Dose (RP2D) [ Time Frame: 6 months ]
    RP2D to be used at Expansion part (Phase 1 part)

  3. Response rate [ Time Frame: 6 months ]
    Response rate in all treated patients (Expansion part)

  4. Overall survival (OS) [ Time Frame: 1 year ]
    OS in all treated patients



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically / cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma
  • Patients who have previously treated with gemcitabine-based chemotherapy (Prior treatment regimen up to 2 is allowed)
  • Patients must have measurable or evaluable disease by RECIST 1.1
  • Eastern Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1
  • Age ≥ 20 years
  • Adequate bone marrow function defined as: Hb ≥ 8 g/dl, absolute neutrophil count (ANC) ≥ 1500/microliter (mcL), Platelets ≥ 100 x10^3/mcL
  • Adequate renal function defined as serum creatinine < 1.6 mg/dl and/or measured creatinine clearance from 24-hour urine collection of ≥ 60 ml/min
  • Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
  • Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage
  • Women of childbearing potential must have a negative pregnancy test within 7 days prior to study treatment
  • Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Evidence of another active cancer that may influence patient outcome, except for nonmelanoma skin carcinoma, melanoma in-situ, in-situ carcinoma of the cervix curatively treated, treated superficial bladder cancer, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment prostate surface antigen (PSA) that is non-detectable
  • Known brain metastases or primary central nervous system tumors with seizures that are not well controlled with standard medical therapy
  • Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements
  • Known HIV positive patient
  • Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris
  • Uncontrolled diabetes mellitus
  • History of a myocardial infarction within 6 months
  • History of a stroke or transient ischemic attack within 6 months
  • Clinically significant peripheral vascular disease
  • Major surgical procedure within 4 weeks
  • Uncontrolled infection
  • Known or suspected allergy to capecitabine
  • Pregnant (positive pregnancy test)
  • Breast-feeding should be discontinued if a nursing mother is to be treated on clinical trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Malabsorption problem that may limit or inhibit the absorption of MEK162
  • History of any organ or bone marrow transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02773459


Locations
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Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Seoul National University Hospital
Investigators
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Principal Investigator: Do-Youn Oh, MD, PhD Seoul National University Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT02773459    
Other Study ID Numbers: BTC-MEK162
First Posted: May 16, 2016    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents