This randomized phase II trial studies how well vandetanib works in preventing head and neck cancer in patients with precancerous head and neck lesions. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of vandetanib may keep cancer from forming in patients with premalignant lesions
PRIMARY OBJECTIVE: I. Determine the effect of ZD6474 (vandetanib) compared to placebo on microvessel density (MVD) from baseline to 3 months in patients at risk for oral squamous cell carcinoma (OSCC) with preneoplastic lesions. SECONDARY OBJECTIVES: I. Change in MVD over 6 months. II. Change in putative targets of ZD6474: tissues will be analyzed by immunohistochemistry (IHC) for phosphorylated epidermal growth factor receptor (pEGFR), EGFR, phosphorylated-vascular endothelial growth factor receptor 2 (pVEGFR2), VEGFR2. III. Change in proliferative index as measured by Ki-67 IHC. IV. Safety, tolerability, and adherence to ZD6474 for 6 months in patients at risk for OSCC. TERTIARY OBJECTIVES: I. Compare OSCC incidence in both study arms (ZD6474 and placebo). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive vandetanib orally (PO) once daily (QD) for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 9 and 12 months and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
20
University of Chicago
Chicago, Illinois, United States
Comparison Between Treatment Groups of the Within-patient Change in MVD Score Following Treatment Initiation
A Wilcoxon ranksum test may be used if the normality assumption is not satisfied. Alternatively, change in MVD may be transformed (e.g. log-transformation) to satisfy the normality assumption. Additional analyses will include linear regression models with treatment effect and other prognostic factors as covariates.
Time frame: Baseline to 3 months
Number of Participants With Adverse Events
Adverse events rate shows the total number of subjects with an AE.
Time frame: Weekly during treatment, up to week 24
Number of Participants Who Adhered to Treatment
Number of participants who Adhered to Treatment
Time frame: Over 6 months
Development of Oral and Other Cancers
Number of patients with new cancer
Time frame: At 6, 9, and 12 months and then ever 6 months for 2 years
Biologic Effect of EGFR and VEGFR2 Inhibition
Effect of treatment on EGFR and VEGFR2 inhibition
Time frame: Baseline and 3 and 6 months
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