Safety Study of Foretinib (GSK1363089) in Adults With Liver Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of foretinib (also known as GSK1363089) when used in the treatment of patients with advanced hepatocellular carcinoma (liver cancer).

Detailed Description
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The purpose of this study is to identify the maximum tolerated dose (MTD) of foretinib (also known as GSK1363089) when used in the treatment of patients with advanced hepatocellular carcinoma (liver cancer), and to assess the safety and tolerability of that dose in this patient population. The MTD will be identified during Phase I, by standard dose-escalation of foretinib. Then Phase II will assess the safety and tolerability of foretinib dosed at MTD.

Official Title
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A Phase 1/2, Open-Label, Multicenter Study of GSK1363089Gin Adult Subjects With Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Foretinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent 18 years or older Eastern Cooperative Oncology Group performance status of 0 or 1 Has histologically or cytologically confirmed advanced (unresectable and/or metastatic) hepatocellular carcinoma (HCC). Has adequate organ system function Has at least 1 target tumor lesion. Has the ability to swallow and retain oral medication Has a life expectancy of at least 12 weeks If male: Agrees to use double-barrier contraception, OR Agrees to complete abstinence from sexual intercourse for 14 days before exposure to investigational product, during the clinical trial, and for at least 21 days after the last dose of investigational product - If female: Is of nonchildbearing potential OR Is of childbearing potential and has a negative serum pregnancy test within 14 days before the first dose of study drug, and agrees to use adequate contraception. Exclusion Criteria: Has previously used an investigational agent or licensed drug that inhibits multiple receptor tyrosine kinases Is currently receiving cancer therapy Is currently receiving treatment with an investigational agent, including an investigational anticancer agent Has a Child-Pugh score >6 Has AEs due to investigational drugs or other medications administered more than 21 days before enrollment that have not recovered to Grade 1 or less with the exception of alopecia greater than Grade 1 Has received local therapy within the following timeframes and the subject has not fully recovered from the prior therapy: Radiotherapy: less than 28 days since completion of prior radiotherapy Chemoembolization, hepatic arterial embolization, percutaneous ethanol injection, or cryoablation: less than 42 days since completion of prior therapy Radiofrequency ablation: less than 60 days since completion of prior therapy Surgery: (1) prior surgical procedure affecting absorption, and (2) less than 28 days since last prior major surgery Has a history or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis Has a history of malabsorption syndrome, any medical condition significantly affecting gastrointestinal function, or resection of the stomach or small bowel Has active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation, or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days Has a known immediate or delayed hypersensitivity or idiosyncratic reaction to drugs chemically related to foretinib. Has a QTcB (Bazett-corrected QT interval) or QTcF (Frederica-corrected QT interval) greater than or equal to 470 msec (or 500 msec if the subject has bundle branch block). Has a history of any one of the following cardiac conditions or procedures within the past 6 months: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Has a history of a cerebrovascular accident within the past 6 months Has Class III or IV heart failure as defined by the New York Heart Association functional classification system Has poorly controlled hypertension (systolic blood pressure of 140 mm Hg or greater or diastolic blood pressure of 90 mm Hg or greater) Has a history of untreated deep venous thrombosis within the past 6 months (e.g., calf vein thrombosis) Has a history of main portal vein thrombosis Has the presence of any nonhealing wound, fracture, or ulcer, or the presence of symptomatic peripheral vascular disease Has had previous or concurrent cancer that is distinct in primary site or histology from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (tumor stages Ta, Tis, and T1). Any cancer curatively treated more than 3 years before study entry is permitted. Has a history of bleeding varices within the past 30 days Has had clinically significant gastrointestinal bleeding within the past 30 days Is a pregnant or lactating female

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Foretinib<br>Phase I starting dose of 30 mg/day escalated to 45 mg/day, de-escalated to 30 mg/day; MTD for Phase II was 30 mg/day | Drug: Foretinib<br>* Phase I starting dose 30 mg/day escalated to 45 mg/day; de-escalated to 30 mg/day. MTD for Phase II dose was 30 mg/day,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose (MTD) |  | up to 2 years | 
| Safety and tolerability of foretinib at the MTD as measured by number and severity of AEs |  | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The antitumor activity of foretinib at the MTD according to RECIST |  | up to 2 years | 
| PK profile of foretinib |  | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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c-MET, VEGFR2, Advanced hepatocellular carcinoma