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

NCT ID: NCT00920192

Last Updated: 2017-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-12
• Study Completion Date: 2015-03-24

Brief Summary

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

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Foretinib

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

Group Type: EXPERIMENTAL

Foretinib

Intervention Type: DRUG

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,

Interventions

Foretinib

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,

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Hong Kong, , Hong Kong

GSK Investigational Site

Tainan City, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Khon Kaen, , Thailand

Countries

Hong Kong; Taiwan; Thailand

References

Singh RP, Patel B, Kallender H, Ottesen LH, Adams LM, Cox DS. Population pharmacokinetics modeling and analysis of foretinib in adult patients with advanced solid tumors. J Clin Pharmacol. 2015 Oct;55(10):1184-92. doi: 10.1002/jcph.546. Epub 2015 Jul 7.

Reference Type: DERIVED

PMID: 25998042 (View on PubMed)

Study Documents

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Other Identifiers

111645

Identifier Type: -

Identifier Source: org_study_id