Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome

Inclusion Criteria

• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of = = 0.5 cm
• Spine: asymptomatic hemangioblastoma, >= 0.5 cm
• Renal: solid mass suspicious for renal cell carcinoma (RCC) >= 1 cm or cystic mass (Bosniak 3-4) >= 1 cm
• Pancreas: solid mass >= 1 cm and = 3 cm but not considered operable
• Eye: asymptomatic peripapillary and/or macular hemangioblastoma, any size
• Adrenal: asymptomatic or controlled pheochromocytoma greater than 1 cm in size
• Patients may have received prior VHL-related systemic therapy, provided not within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
• Absolute neutrophil count (ANC) >= 1.5 X 10^9/L
• Hemoglobin >= 9 g/dL (5.6 mmol/L)
• Subjects may not have had a transfusion within 7 days of screening assessment
• Platelets >= 100 X 10^9/L
• Prothrombin time (PT) or international normalized ratio (INR) = 2.0 mg/dL: calculated creatinine clearance (ClCR) >= 50 mL/min
• Urine protein to creatinine ratio (UPC) = 1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value = 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value = 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT; childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception GlaxoSmithKline (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:
• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product
• Oral contraceptive
• Injectable progestogen
• Implants of levonorgestrel
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device (IUD)
• Male partner sterilization
• Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository); female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug

Exclusion Criteria

• Prior malignancy. Subjects who have had another non VHL related malignancy and have been disease-free for 2 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product in