MEK162 in Combination With Capecitabine in Advanced Biliary Tract Cancer

September 27, 2019 updated by: Seoul National University Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • MEK162, xeloda

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (Actual)

January 7, 2019

Study Completion (Actual)

January 7, 2019

Study Registration Dates

First Submitted

May 13, 2016

First Submitted That Met QC Criteria

May 13, 2016

First Posted (Estimate)

May 16, 2016

Study Record Updates

Last Update Posted (Actual)

September 30, 2019

Last Update Submitted That Met QC Criteria

September 27, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BTC-MEK162

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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