A Study of GSK2256098 and Trametinib in Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This is a phase 2 study (the second phase in testing a new drug or combination to see how effect the drug or combination is) of investigational drugs GSK2256098 and Trametinib. The purpose of the study is to evaluate the antitumor activity of GSK2256098 and Trametinib in patients with advanced pancreatic cancer.

Detailed Description
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Trametinib is a drug that works by binding to and blocking certain proteins called mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working. MEK1 and MEK2 are important proteins that contribute to the growth of cancer cells. GSK2256098 is a drug that blocks a protein called focal adhesion kinase-1 (FAK) which is an important protein that contribute to the growth of cancer cells.

Official Title
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Molecular Basket Trial In Multiple Malignancies With Common Target Pathway Aberrancies: A Phase II Trial of GSK2256098 and Trametinib in Patients With Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer, Adenocarcinoma

Intervention / Treatment
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* Drug: GSK2256098
* Drug: Trametinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years or older, able to give written consent Pancreatic adenocarcinoma that is not responsive to standard therapies or for which there is no approved or curative therapy or for patients who refuse standard therapy Have clinical, radiographic, or serologic progression after one prior line of chemotherapy for advanced disease. Patients who have received two or more prior lines of chemotherapy for advanced disease are not eligible. Performance Status score of 0 or 1 Measureable disease by RECIST version 1.1 Able to swallow and retain oral medication Have malignant disease that is amenable to biopsy and agree to collection of mandatory tumor biopsy samples. Agrees to use contraception Not pregnant Adequate organ system function Exclusion Criteria: Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including investigational drugs within 28 days or 5 half lives. No prior MEK inhibitor, RAF inhibitors or a FAK inhibitors Current use of a prohibited medication Unresolved toxicity greater than Grade 1 from previous anticancer therapy unless the ongoing toxicity will not introduce additional risk factors and will not interfere with the study procedures. Presence of active GI disease or other condition that could affect gastrointestinal absorption or predisposed to GI ulceration Evidence of mucosal or internal bleeding Anticoagulation with warfarin Major surgery within the last four weeks Malignancies related to HIV or HBV/HCV Known active infection requiring parenteral or oral anti-infective treatment Leptomeningeal disease. Brain metastases QTcF interval ≥ 480 msecs History or evidence of current clinically significant uncontrolled arrhythmias History of acute coronary syndromes, myocardial infarction, coronary angioplasty, or stenting or bypass grafting within six months of screening. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. Other clinically significant ECG abnormalities Intra-cardiac defibrillators. Presence of cardiac metastases. Serious or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety or providing informed consent. Known immediate or delayed hypersensitivity to any of the components of the study treatment(s). Evidence of severe or uncontrolled systemic diseases Pregnant or lactating History of retinal vein occlusion History of interstitial lung disease or pneumonitis

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: GSK2256098 and Trametinib<br>GSK2256098, orally, at 0.375 or 0.5 mg, once daily, continuously every 28 day cycles. Trametinib, orally at 250 mg or 500 mg, twice daily, continuously every 28 day cycles. | Drug: GSK2256098<br>* Small molecule inhibitor of focal adhesion kinase (FAK)<br>Drug: Trametinib<br>* Allosteric inhibitor of mitogen-activated extracellular signal-regulated kinase (MEK)1 and MEK2 activation and kinase activity.<br>* Other names: Mekinist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who experience complete response, partial response, or stable disease |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events based on frequency and proportion of total patients, by system organ class and preferred term. |  | 2 years | 
| Percentage of patients achieving either a complete or partial tumor response. |  | 2 years | 
| Interval between the date of randomization and the earliest date of disease progression or death due to any cause |  | 2 years | 
| Interval between the first date of CR or PR and the earliest date of disease progression or death due to any cause. |  | 2 years |