• Safety and tolerability [ Designated as safety issue: Yes ]
• Time to progression and progression-free survival [ Designated as safety issue: No ]
• Effect on non-renal Von Hippel-Lindau-associated tumors [ Designated as safety issue: No ]
• Effect on circulating endothelial cells and endothelial progenitor cells and utility of these markers as surrogates of angiogenesis inhibition [ Designated as safety issue: No ]
• Effect on plasma VEGF and soluble VEGFR2 [ Designated as safety issue: No ]

• Safety and tolerability
• Time to progression and progression-free survival
• Effect on non-renal tumors
• Effect on circulating endothelial cells and endothelial progenitor cells and utility of these markers as surrogates of angiogenesis inhibition
• Effect on plasma VEGF and soluble VEGFR2

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well vandetanib works in treating patients with Von Hippel-Lindau syndrome and kidney tumors.

OBJECTIVES:

Primary

• To assess the overall response rate in patients with Von Hippel-Lindau-associated renal tumors treated with vandetanib.

Secondary

• To study the safety and tolerability of vandetanib.
• To evaluate time to progression and progression-free survival in these patients.
• To study the effect of vandetanib on non-renal tumors associated with von Hippel Lindau disease (e.g., pancreatic tumors, pheochromocytoma, or CNS hemangioblastomas).
• To investigate the effect of vandetanib on circulating endothelial cells and endothelial progenitor cells and to explore the utility of these markers as surrogates of angiogenesis inhibition.
• To investigate the effect of vandetanib on biomarkers of angiogenesis such as plasma VEGF and soluble VEGFR2.

OUTLINE: Patients receive oral vandetanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically during treatment to assess angiogenesis biomarkers such as VEGF, circulating endothelial cells, and circulating endothelial progenitor cells. Samples are analyzed by flow cytometry, real-time RT-PCR, and gene expression.

After completion of study treatment, patients are followed periodically.

• Kidney Cancer
• Von Hippel-Lindau Syndrome

• Drug: vandetanib
• Genetic: gene expression analysis
• Genetic: reverse transcriptase-polymerase chain reaction
• Other: flow cytometry
• Other: laboratory biomarker analysis

DISEASE CHARACTERISTICS:

• Diagnosis of Von Hippel-Lindau disease

• At least one measurable renal tumor (renal cell carcinoma [RCC]) as defined by RECIST

  • Tumors localized to kidney and metastatic RCC allowed
• No known brain metastases (unless adequately resected or irradiated with no evidence of recurrence for at least 6 months)

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-2
• Life expectancy > 3 months
• WBC ≥ 3,000/μL
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min
• AST and ALT < 2.5 x ULN
• Total bilirubin < 1.5 x ULN (3 times ULN for patients with Gilbert disease)
• Alkaline phosphatase ≤ 2.5 x ULN (5 times ULN if liver metastases are present)
• Potassium > 4.0 mEq/L
• Not nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2 months after completion of study treatment
• LVEF ≥ 45% by MUGA or ECHO

• Measurable QTc and QTc ≤ 480 msec with Bazett's correction by ECG

  • QTc ≤ 460 msec if receiving a drug with risk of QTc prolongation

Exclusion criteria:

• Calcium (ionized calcium or adjusted for albumin) or magnesium concentrations outside normal limits despite optimal supplementation/correction
• Prior or concurrent non-Von Hippel-Lindau associated malignancy except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or any other malignancy from which the patient has remained disease free for more than 5 years
• Clinically significant cardiac event, including symptomatic heart failure, myocardial infarction, or angina within the past 3 months
• Presence of any cardiac disease, that in the opinion of the principal investigator, increases the risk of ventricular arrhythmia
• History of clinically significant symptomatic arrhythmia (CTC grade 3) (e.g., multifocal premature ventricular contraction, bigeminy, trigeminy, or ventricular tachycardia) requiring treatment or a symptomatic sustained ventricular tachycardia
• Prior history of QTc prolongation while taking other medications and subsequently required discontinuation of the medication
• Congenital long QT syndrome or a first-degree relative with unexplained sudden death under the age of 40 years
• Uncontrolled atrial fibrillation
• Presence of left bundle branch block
• Hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg) uncontrolled by medical therapy

• History of uncontrolled significant intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements
• Known HIV positivity
• Currently active diarrhea condition that would affect the ability to absorb vandetanib or tolerate further diarrhea
• Known bleeding disorders
• Known hypersensitivity to vandetanib or any of its excipients
• Inadequately healed abscess as a result of prior surgery

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• At least 4 weeks since other prior surgery or investigational therapy for von Hippel-Lindau disease
• At least 4 weeks since any prior and no concurrent major elective surgery
• More than 4 weeks since prior chemotherapy or radiotherapy
• More than 4 weeks since prior and no other concurrent investigational or non-approved agents
• No concurrent 5HT-3 antagonists
• No prior or concurrent potent inducers of CYP3A4 function (i.e., rifampin, phenytoin, carbamazepine, barbiturates, or Hypericum perforatum [St. John wort])
• No concurrent therapeutic anticoagulation
• No concurrent drugs that could induce Torsades de pointes
• No concurrent antiretroviral therapy for HIV-positive patients
• No concurrent systemic anti-neoplastic therapy for von Hippel-Lindau-associated tumors