Phase 2 Study of GSK1363089 (Formerly XL880) in Adults With Squamous Cell Cancer of the Head and Neck
Condition: Neoplasms, Head and Neck
MeSH terms: Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Head and Neck Neoplasms
Intervention: GSK1363089 (foretinib)
Intervention description: Multitargeted tyrosine kinase inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: VEGFR2; XL880; foretinib; Squamous Cell Cancer of the Head and Neck; MET; GSK1363089

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.