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

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.