Phase 2 Study of GSK1363089 (Formerly XL880) in Adults With Squamous Cell Cancer of the Head and Neck

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00725764
First received: July 28, 2008
Last updated: May 31, 2012
Last verified: February 2011
  Purpose

This study is being conducted to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in adult subjects with squamous cell carcinoma of the head and neck (SCCHN). GSK1363089 is a new chemical entity that inhibits multiple receptor tyrosine kinases (RTKs) with growth-promoting and angiogenic properties. The primary targets of GSK1363089 are the HGF and vascular endothelial growth factor (VEGF) RTK families (eg, MET, VEGFR2/kinase insert domain receptor [KDR]). Since MET overexpression has been associated with poorer prognosis and MET tyrosine kinase mutations have been reported in SCCHN, inhibition of MET receptor and VEGFR2/KDR activation by agents such as GSK1363089 may be of therapeutic benefit in this patient population.


Condition Intervention Phase
Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
Neoplasms, Head and Neck
Drug: GSK1363089 (foretinib)
Phase 2

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 2 Study of the MET RTK Inhibitor GSK1363089 (Formerly XL880) in Subjects With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To determine the best confirmed response rate of GSK1363089 treatment in subjects with SCCHN [ Time Frame: November 2009 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the progression-free survival, duration of response, and overall survival in subjects with SCCHN treated with GSK1363089. [ Time Frame: November 2009 ] [ Designated as safety issue: No ]
  • To further characterize the pharmacokinetic (PK) parameters of GSK1363089 in subjects with SCCHN [ Time Frame: November 2009 ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: August 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
Participants who qualified for study entry received 240 mg of GSK1363089 (foretinib) on a 5-day on 9-day off schedule every 2 weeks.
Drug: GSK1363089 (foretinib)
Multitargeted tyrosine kinase inhibitor
Other Name: GSK1363089 (formerly XL880)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has a histologically or cytologically confirmed diagnosis of SCCHN and
  • has recurrent and/or metastatic disease
  • is not eligible for curative intent surgery or radiotherapy
  • has no history of uncontrolled tumor bleeding including hemoptysis in patients with documented pulmonary metastasis.
  • The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as =20 mm with conventional techniques, or as =10 mm with spiral computerized tomography (CT) scan.
  • Subject is capable of swallowing capsules.
  • Fifteen unstained slides of tumor tissue, archival or fresh, or paraffin block are available, and there - confirmation that samples have been sent for analysis at the central laboratory.
  • The subject is at least 18 years old.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status =1.
  • In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level =20 µg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.
  • The subject has organ and marrow function as follows: absolute neutrophil count (ANC) =1500/mm3, platelets =100,000/mm3, hemoglobin =9 g/dL, bilirubin =1.5 mg/dL, serum creatinine =1.5 mg/dL and/or calculated creatinine clearance =60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 times the upper limit of normal if no liver involvement or =5 times the upper limit of normal with liver involvement.
  • The subject has signed the informed consent document.
  • Sexually active subjects must use a medically accepted method of contraception during the course of the study.
  • Female patients of childbearing potential must have a negative pregnancy test at enrollment.
  • The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed =5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).

Exclusion Criteria:

  • The subject has received radiation to >25% of his or her bone marrow within 30 days of GSK1363089 treatment.
  • The subject has received an investigational drug within 30 days (or <5.5 half lives) of the first dose of study drug.
  • The subject has received more than one regimen of systemic anticancer therapy for disease that has recurred or is metastatic. This may include either single-agent or combination cytotoxic chemotherapy with radiotherapy or anti-EGFR treatment (eg, cetuximab). Adjuvant or neoadjuvant systemic chemotherapy does not count as a regimen for recurrent or metastatic disease.
  • The subject has progressed within 6 months after completion of curative intent (definitive) treatment for localized/locoregionally advanced disease.
  • The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade =1 from adverse events (AEs) due to investigational drugs or other medications that were administered more than 30 days before study enrollment with the sole exception of persistent Grade 2 peripheral neuropathy in patients who have previously received platinum-based therapy.
  • The subject has known brain metastases.
  • The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active alcoholism, or psychiatric illness that would limit compliance with study requirements.
  • The subject is pregnant or breastfeeding.
  • The subject is known to be positive for the human immunodeficiency virus (HIV).
  • The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation.
  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: NCT00725764

Locations
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30309
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60637
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46254
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55407-3799
United States, Missouri
GSK Investigational Site
St Louis, Missouri, United States, 63110
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, South Carolina
GSK Investigational Site
Charleston, South Carolina, United States, 29403
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
GSK Investigational Site
San Antonio, Texas, United States, 78229
United States, West Virginia
GSK Investigational Site
Morgantown, West Virginia, United States, 28506
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Seiwert T, Swann S,Kurz H, Bonate P, McCallum S, Sarantopoulos J A Phase II study of the efficacy and safety of foretinib, a novel receptor tyrosine kinase inhibitor, given on an intermittent five days on nine days off (5/9) schedule in patients with recurrent or metastatic squamous cell cancer of the head and neck (SCCHN) Mol Cancer Ther 2009, 8 (12 suppl), B6

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00725764     History of Changes
Obsolete Identifiers: NCT00482326
Other Study ID Numbers: MET111646
Study First Received: July 28, 2008
Last Updated: May 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
VEGFR2
XL880
foretinib
Squamous Cell Cancer of the Head and Neck
MET
GSK1363089

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Squamous Cell
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 20, 2014