Last updated: 11/04/2018 09:13:00
Phase 2 Study of GSK1363089 (formerly XL880) in Adults with Squamous Cell Cancer of the Head and Neck
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants achieving best overall response
Timeframe: Approximately up to 1 year
Percentage of participants with objective response rate (ORR)
Timeframe: Approximately up to 1 year
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to 20 months
Number of participants with abnormalities of common toxicity criteria for adverse events (CTCAE) grade 3 in laboratory parameters (clinical chemistry and hematology)
Timeframe: Up to 20 months
Number of participants with abnormalities in urinalysis
Timeframe: Week 5 [Day 29]
Secondary outcomes:
Duration of progression-free survival
Timeframe: Approximately up to 1 year
Duration of Overall Survival
Timeframe: Approximately up to 1 year
Duration of Stable Disease
Timeframe: Approximately up to 1 year
Percentage participants with disease stabilization rate
Timeframe: Approximately up to 1 year
Maximum plasma concentration (Cmax) of foretinib in participants with squamous cell carcinoma of the head and neck (SCCHN)
Timeframe: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Time to maximum plasma concentration (tmax) of foretinib in participants with SCCHN
Timeframe: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Area under the concentration-time curve (AUC) of foretinib in participants with SCCHN
Timeframe: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Elimination half-life (t1/2) of foretinib in participants with SCCHN
Timeframe: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Apparent oral clearance
Timeframe: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Apparent volume of distribution
Timeframe: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Interventions:
Drug: GSK1363089 (foretinib)
Enrollment:
14
Observational study model:
Not applicable
Primary completion date:
2009-02-05
Time perspective:
Not applicable
Clinical publications:
Seiwert T, Sarantopoulos J, Kallender H, McCallum S, Keer, H, Blumenschein G.Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck .Invest New Drugs.2013;31(2):417-424
Medical condition
Neoplasms, Head and Neck
Product
foretinib
Collaborators
Not applicable
Study date(s)
August 2007 to May 2009
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- The subject has a histologically or cytologically confirmed diagnosis of SCCHN and
- has recurrent and/or metastatic disease
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Houston, Texas, United States, 77030
Status
Will Be Recruiting
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46254
Status
Terminated/Withdrawn
Location
GSK Investigational Site
St Louis, Missouri, United States, 63110
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30309
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chicago, Illinois, United States, 60637
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55407-3799
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Charleston, South Carolina, United States, 29403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Morgantown, West Virginia, United States, 28506
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2009-02-05
Actual study completion date
2009-02-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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