INCLUSION CRITERIA:
A subject must meet the following criteria to be eligible for the study:
1. The subject must have a histologically confirmed diagnosis of PRC manifest as either metastatic disease or bilateral multifocal renal tumors localized to the kidneys, excepting subjects with bilateral, multifocal renal tumors with a documented germline c-MET mutation consistent with hPRC who may be enrolled without a tissue diagnosis.
2. 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 greater than or equal to 20 mm with conventional techniques, or as greater than or equal to 10 mm with spiral computerized tomography (CT) scan.
3. The subject is at least 18 years old.
4. The subject has an ECOG performance status less than or equal to 2.
5. The subject has unstained slides of tumor tissue, archival or from a recent biopsy, or paraffin block available for c-MET pathway analysis (excepting subjects with bilateral, multifocal renal tumors with a documented c-MET mutation consistent with hPRC, who may be enrolled without tissue as described above if such samples do not exist).
6. When exposed to the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level greater than or equal to 20 microg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.
7. The subject has a QTcB (Bazett corrected) or QTcF (Frederica corrected) less than 470 msec.
8. The subject has organ and marrow function as follows: absolute neutrophil count (ANC) greater than or equal to 1500/mm(3), platelets greater than or equal to 100,000/mm(3), hemoglobin greater than or equal to 9 g/dL, bilirubin less than or equal to 1.5 mg/dL, serum creatinine less than or equal to 1.5 mg/dL and/or calculated creatinine clearance greater than or equal to 60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal if no liver involvement or less than or equal to 5 times the upper limit of normal with liver involvement.
9. The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
10. Sexually active subjects must use an accepted method of contraception during the course of the study.
11. Female patients of childbearing potential must have a negative pregnancy test at enrollment.
12. The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed greater than 5 years ago with no current evidence of disease).
EXCLUSION CRITERIA:
A subject who meets any of the following criteria is ineligible for the study:
1. The subject has received radiation to greater than or equal to 25% of his or her bone marrow within 14 days of GSK1363089 treatment.
2. The subject has received more than 1 prior anticancer therapy.
3. The subject has received any systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR agents, or investigational drug within 14 days of the first dose of study drug.
4. The subject has received an inhibitor of c-MET (eg, antibodies to HGF, small molecule inhibitors of c-MET).
5. The subject has not recovered to NCI CTCAE v3.0 Grade less than or equal to 1 from AEs due to investigational drugs or other medications that were administered more than 14 days before study enrollment.
6. The subject has known brain metastases.
7. The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. For the purposes of this protocol, hypertension will be considered uncontrolled if despite optimal antihypertensive therapy either the systolic blood pressure (SBP) is greater than 140 mm Hg or diastolic blood pressure (DBP) is greater than 90 mm Hg for a sustained period of time (greater than 24 hours) or results in symptoms.
8. The subject is pregnant or breastfeeding.
9. The subject is known to be positive for the human immunodeficiency virus (HIV) and is receiving antiretroviral therapies. Subjects known to be HIV positive who do not require antiretroviral therapy will be eligible if they meet other entry criteria.
10. The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation.
11. The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/13/2009