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First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01828034
Recruitment Status : Completed
First Posted : April 10, 2013
Last Update Posted : June 4, 2019
Array BioPharma
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to test an investigational combination of drugs for bile duct or gallbladder cancers. Gemcitabine and cisplatin are two forms of chemotherapy commonly used in combination to treat bile duct and gallbladder cancers. The investigators are looking to improve treatment results. They will attempt to do so by adding the drug MEK162 to the treatment plan. MEK162 acts by blocking a protein called MEK 1/2 which helps cancer cells grow and divide. This study will help answer the question of whether MEK162 is a helpful drug in patients with bile duct or gallbladder cancers when given with gemcitabine and cisplatin.

Condition or disease Intervention/treatment Phase
Advanced Biliary Tract Carcinoma Drug: Gemcitabine Drug: Cisplatin Drug: MEK162 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma
Actual Study Start Date : April 2013
Actual Primary Completion Date : May 30, 2019
Actual Study Completion Date : May 30, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Gemcitabine, Cisplatin and MEK162
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 & 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
Drug: Gemcitabine
Drug: Cisplatin
Drug: MEK162

Primary Outcome Measures :
  1. MTD of MEK162 - Phase I [ Time Frame: 1 year ]
    In the phase I portion, up to 18 patients will be enrolled in classic 3+3 cohort dose escalation design to identify the MTD of MEK162 when administered with gemcitabine and cisplatin given weeks 2 and 3 of a 3 week cycle .

  2. six-month progression free survival - phase II [ Time Frame: 6 months ]
    An exact binomial single stage design will be used to discriminate between true 6-month PFS rates of 59% vs. 82%, and between true response rates of 26% and 50%.

  3. objective response rate - phase II [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. median PFS [ Time Frame: 1 year ]
    progression free survival will be calculated from study entry to documented disease progression or death from any cause, whatever occurs first.

  2. median overall survival [ Time Frame: 1 year ]
    (survival) will be calculated from study entry to death or last follow up

  3. safety/toxicity profile [ Time Frame: 2 years ]
    All toxicities will be rated as per the NCI Common Toxicity Criteria, version 4.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically / cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma. Combined cholangiocarcinoma and hepatocellular carcinoma is allowed.
  • Patients must have measurable disease by RECIST 1.1
  • KPS ≥ 80%
  • Age ≥ 18 years
  • Adequate bone marrow function defined as: Hb ≥ 8 g/dl, ANC ≥ 1.5 K/mcL, Platelets ≥ 100 K/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, ALT/AST ≤ 5 x ULN.
  • Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage.

Adequate cardiac function defined as ejection fraction ≥ 45% as determined by transthoracic echocardiogram or MUGA

  • Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of ≥ 20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan
  • 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:

  • Any previous chemotherapy, biologic therapy, or investigational agent, except for adjuvant therapy as single agents and/or as radio-sensitizing agents limited to 5-fluorouracil and gemcitabine. Patient must have completed adjuvant therapy no less than six months prior to accrual.
  • Evidence of another active cancer that may influence patient outcome as determined by the Principal Investigator (PI) or co-Principal Investigator (co-PI), 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 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.
  • 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 gemcitabine or cisplatin
  • 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 MEK 162
  • Patients with a history or current known evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy at baseline that would be considered a risk factor for CSR or RVO.
  • 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 identifier (NCT number): NCT01828034

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United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Array BioPharma
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Principal Investigator: Ghassan Abou-Alfa, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT01828034    
Other Study ID Numbers: 13-004
First Posted: April 10, 2013    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: June 2019
Keywords provided by Memorial Sloan Kettering Cancer Center:
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs