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Von Hippel-Lindau

Investigator(s):
W. Marston Linehan, M.D. Principal Investigator Phone: 301-496-6353 linehanm@mail.nih.gov	Ramaprasad Srinivasan, M.D. Protocol Chair Phone: 301-496-6353 ramasrin@mail.nih.gov
Referral Contact(s):
Sarah Fowler, R.N. Protocol Coordinator Phone: 301-435-6255 fowlers@mail.nih.gov

No known brain metastases (unless adequately resected or irradiated with no evidence of recurrence for ≥ 6 months)
Recovered from all prior therapy
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’s wort])
No concurrent therapeutic anticoagulation
No concurrent drugs that could induce Torsades de pointes
No concurrent systemic anti-neoplastic therapy for von Hippel-Lindau-associated tumors
≥ 18 years of age
ECOG performance status 0–2
WBC count ≥ 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/ALT < 2.5 x ULN
Total bilirubin < 1.5 x ULN (3 x ULN for patients with Gilbert disease)
Alkaline phosphatase ≤ 2.5 x ULN (5 x ULN if liver metastases are present)
Potassium concentration > 4.0 mEq/L
Not pregnant or nursing; 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

No calcium (ionized calcium or adjusted for albumin) or magnesium concentrations outside normal limits despite optimal supplementation/correction
No prior or concurrent non Von Hippel Lindau associated malignancy except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ or any other malignancy from which the patient has remained disease free > 5 years
No prior history of QTc prolongation while taking other medications; no congenital long QT syndrome or first degree relative with unexplained sudden death under the age of 40 years
No uncontrolled atrial fibrillation
No presence of left bundle branch block
No hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg) uncontrolled by medical therapy
No history of uncontrolled significant intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with study requirements
Not requiring antiretroviral therapy for HIV
No currently active diarrhea condition that would affect the ability to absorb vandetanib or tolerate further diarrhea
No known bleeding disorders
No known hypersensitivity to vandetanib or any of its excipients

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 may be followed periodically as required

This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
There is no charge for medical care received at NIH Clinical Center.

PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 5/14/09
Updated: 2/14/08