MEK162 in Combination With Capecitabine in Advanced Biliary Tract Cancer

NCT02773459 | Completed Phase 1 DMC

• 1 other identifier: BTC-MEK162
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  MTD in all treated population (Phase 1 part)

  6 months

• Progression-free survival (PFS)

  PFS in all treated population (Expansion part)

  3 months

Secondary Outcomes (4)

• Dose-limiting Toxicity (DLT)

  6 months

• Recommended Phase 2 Dose (RP2D)

  6 months

• Response rate

  6 months

• Overall survival (OS)

  1 year

Study Arms (2)

Phase 1 part

EXPERIMENTAL

to assess the maximal tolerated dose (MTD) of MEK162+Capecitabine combination

Drug: MEK162+capecitabine

Expansion part

EXPERIMENTAL

to assess the efficacy (PFS) of MEK162+Capecitabine combination

Drug: MEK162+capecitabine

Interventions

MEK162+capecitabine DRUG

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.

Also known as: MEK162, xeloda

Expansion part; Phase 1 part

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Related Publications (1)

• Kim JW, Lee KH, Kim JW, Suh KJ, Nam AR, Bang JH, Bang YJ, Oh DY. Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway: phase Ib study. Br J Cancer. 2019 Aug;121(4):332-339. doi: 10.1038/s41416-019-0523-5. Epub 2019 Jul 17.

  PMID: 31312030 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

binimetinib; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Do-Youn Oh, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 16, 2016
• Study Start: April 1, 2016
• Primary Completion: January 7, 2019
• Study Completion: January 7, 2019
• Last Updated: September 30, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)