A Study of MEK162 With Gemcitabine and Oxaliplatin in Biliary Cancer

Study Overview
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Brief Summary
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This is a phase I study (an early study to check the safety of a new drug or drug combination) to find the safest and most tolerated dose of the combination of oxaliplatin with gemcitabine and MEK 162 in patients with biliary cancer (including gallbladder cancers and cancers associated with the bile ducts leading from the gallbladder and to and from the liver) that is not curable by surgery and/or has spread beyond the biliary tree (place where cancer started). Everyone will receive the same standard doses of oxaliplatin and gemcitabine but may receive different doses of MEK 162. MEK 162 is a new drug which plays an important role in the regulation of cell growth and has been shown to shrink tumours in patients with biliary cancer and other types of human cancers. This type of drug has also been shown to shrink tumours when given in combination with cisplatin and gemcitabine in research studies done in animals and in some patients with biliary cancer.

Official Title
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A Phase I Trial of MEK Inhibitor MEK 162 Combined Sequentially With Gemcitabine-Oxaliplatin (GEMOX) in Patients With Advanced Biliary Cancer

Conditions
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Biliary Tract Carcinoma, Gallbladder Carcinoma

Intervention / Treatment
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* Drug: MEK 162
* Drug: Gemcitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological or cytological diagnosis of non-resectable, recurrent or metastatic biliary tract (intra- or extra-hepatic) or gallbladder carcinoma. Have measurable disease. Not received prior systemic therapy for advanced biliary cancer. Age 18 years of age or older. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Estimated life expectancy is greater than 3 months. Have adequate hematological function. Have adequate cardiac function. All radiology studies performed within 4 weeks prior to the start of therapy. No evidence of active uncontrolled infection. Ability to understand and willing to sign a written informed consent document. Ongoing prior toxicities related to previous treatments received to grade 1 or less at time of registration. Able to take oral medications. Exclusion Criteria: Progressing within 6 months of receiving adjuvant treatment for biliary tract cancer. Not have received prior chemotherapy for non-resectable or metastatic disease or MEK inhibitor. Histopathological or cytological diagnosis of ampullary carcinoma. Incomplete recovery from previous surgery. Undergoing current treatment with curative intent. History of prior malignancy that could interfere with the response evaluation. Any evidence of severe or uncontrolled systemic diseases or laboratory findings that may affect participation in the trial. Any psychiatric or other disorder likely to impact on informed consent. Pregnant or nursing (lactating) women. Agree to use highly effective methods of contraception throughout the study and for 6 months after study drug discontinuation. Significant cardiac disease. History of retinal degenerative disease. History of Gilbert's syndrome. Known positive serology for HIV, active hepatitis B, and/or active hepatitis C infection. Neuromuscular disorders that are associated with elevated creatine kinase. Planning on embarking on a new strenuous exercise regimen after first dose of study treatment. Impairment of gastrointestinal function or gastrointestinal disease. Any other condition that would contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEK 162, gemcitabine, and oxaliplatin<br>MEK 162 (30 mg or 45 mg by mouth), twice a day, every day. Gemcitabine (1000 mg/m2 by vein), followed by oxaliplatin (85 mg/m2 by vein) every 2 weeks. | Drug: MEK 162<br> <br> Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Oxaliplatin<br> <br> * Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total incidence of grade 3 and 4 adverse events |  | 2 years | 
| Total rate of grade 3 and 4 adverse events |  | 2 years | 
| Maximum dose level at which 0/3 patients or 1/6 patients experience dose-limiting toxicity |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with objective response rate |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEK162, Gemcitabine, Oxaliplatin, Non-resectable, Recurrent or metastatic