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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00920192
First received: June 12, 2009
Last updated: September 5, 2013
Last verified: August 2013
  Purpose

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).


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Foretinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Multicenter Study of GSK1363089Gin Adult Subjects With Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The maximum tolerated dose (MTD) [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of foretinib at the MTD as measured by number and severity of AEs [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The antitumor activity of foretinib at the MTD according to RECIST [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • PK profile of foretinib [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: September 2009
Estimated Study Completion Date: May 2014
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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,

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920192

Locations
Hong Kong
GSK Investigational Site
Hong Kong, Hong Kong
Taiwan
GSK Investigational Site
Tainan, Taiwan, 70428
GSK Investigational Site
Taipei, Taiwan, 112
GSK Investigational Site
Taipei, Taiwan, 110
Thailand
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Bangkok, Thailand, 10700
GSK Investigational Site
Khon Kaen, Thailand, 40002
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00920192     History of Changes
Other Study ID Numbers: 111645
Study First Received: June 12, 2009
Last Updated: September 5, 2013
Health Authority: Taiwan: Department of Health
Thailand: Ministry of Public Health
Hong Kong: Department of Health
Korea: Korea Food & Drug Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
c-MET
VEGFR2
Advanced hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 16, 2014