Clinical trial NCT00725764: Phase 2 Study of GSK1363089 (Formerly XL880) in Adults With Squamous Cell Cancer of the Head and Neck
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Head and Neck
Keywords: VEGFR2
XL880
foretinib
Squamous Cell Cancer of the Head and Neck
MET
GSK1363089
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-30
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants Achieving Best Overall Response
timeFrame: Approximately up to 1 year
measure: Percentage of Participants With Objective Response Rate (ORR)
timeFrame: Approximately up to 1 year
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 20 months
measure: 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
measure: Number of Participants With Abnormalities in Urinalysis
timeFrame: Week 5 [Day 29]
Secondary outcomes:
measure: Duration of Progression-free Survival
timeFrame: Approximately up to 1 year
measure: Duration of Overall Survival
timeFrame: Approximately up to 1 year
measure: Duration of Stable Disease
timeFrame: Approximately up to 1 year
measure: Percentage Participants With Disease Stabilization Rate
timeFrame: Approximately up to 1 year
measure: 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
measure: 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
measure: 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
measure: 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
measure: Apparent Oral Clearance
timeFrame: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
measure: Apparent Volume of Distribution
timeFrame: Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lebanon
country: United States
facility: GSK Investigational Site
state: New Hampshire
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: