Vandetanib in Preventing Head and Neck Cancer in Patients With Precancerous Head and Neck Lesions
Condition: Lip and Oral Cavity Squamous Cell Carcinoma; Oral Cavity Verrucous Carcinoma; Precancerous Condition
MeSH terms: Carcinoma; Carcinoma, Verrucous; Precancerous Conditions; Squamous Cell Carcinoma of Head and Neck
Intervention: vandetanib; placebo; immunohistochemistry staining method; laboratory biomarker analysis; biopsy; pharmacological study
Intervention description: Given PO; Given PO; Correlative studies; Correlative studies; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological/cytological confirmation of oral cavity dysplasia and one of three
             additional criteria:

          -  Prior history of OSCC

          -  Loss of heterozygosity (LOH) at 3p or 9p

          -  Expression by immunohistochemistry (IHC) of budding uninhibited by benzimidazoles 3
             (BUB3)/sex determining region Y (SOX4)

          -  Provision of informed consent

          -  Females of child bearing age must have a negative serum pregnancy test within 7 days
             of first dose of study drug

          -  Patients must not have been taking steroids or are on a stable dose of steroids for at
             least 14 days before enrollment

          -  Patients must have a Karnofsky Performance Score of 70% or above

        Exclusion Criteria:

          -  History of malignancy within the last 5 years other than squamous cell carcinoma of
             the head and neck (SCCHN) and superficial non-melanoma skin cancer; patients with a
             history of SCCHN must be free of active carcinoma

          -  Currently receiving treatment for any malignancy

          -  Serum bilirubin > 1.5x the upper limit of reference range (ULRR)

          -  Creatinine clearance =< 30 mL/minute (calculated by Cockcroft-Gault formula)

          -  Potassium, < 4.0 mmol/L despite supplementation; or above the Common Terminology
             Criteria for Adverse Events (CTCAE) grade 1 upper limit

          -  Magnesium below the normal range despite supplementation, or above the CTCAE grade 1
             upper limit

          -  Serum calcium above the CTCAE grade 1 upper limit; in cases where the serum calcium is
             below the normal range, 2 options would be available: 1) the calcium adjusted for
             albumin is to be obtained and substituted for the measured serum value; exclusion is
             to then be based on the adjusted for albumin values falling below the normal limit; 2)
             Determine the ionized calcium levels; if these ionized calcium levels are out of
             normal range despite supplementation, then the patient must be excluded

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULRR

          -  Alkaline phosphatase (ALP) > 2.5 x ULRR

          -  Evidence of severe or uncontrolled systemic disease or any concurrent condition which
             in the Investigator's opinion makes it undesirable for the patient to participate in
             the trial or which would jeopardize compliance with the protocol

          -  Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena
             cava syndrome [SVC], New York Heart Association [NYHA] classification of heart disease
             > 2 within 3 months before entry; or presence of cardiac disease that, in the opinion
             of the Investigator, increases the risk of ventricular arrhythmia

          -  History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy,
             trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is
             symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained
             ventricular tachycardia; atrial fibrillation, controlled on medication is not excluded

          -  QTc prolongation with other medications that required discontinuation of that
             medication

          -  Congenital long QT syndrome or 1st degree relative with unexplained sudden death under
             40 years of age

          -  Presence of left bundle branch block (LBBB)

          -  QTc with Bazett's correction that is unmeasurable or ≥450 msec on screening
             electrocardiogram (ECG); (Note: If a subject has a QTc interval >= 450 msec on
             screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the
             average QTc from the three screening ECGs must be < 450 msec in order for the subject
             to be eligible for the study)

          -  Any concurrent medication with a known risk of inducing Torsades de Pointes, that in
             the investigator's opinion cannot be discontinued

          -  Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin,
             carbamazepine, phenobarbital and St. John's Wort) of Cytochrome P450 3A4 (CYP3A4)
             function

          -  Hypertension not controlled by medical therapy (systolic blood pressure greater than
             160 mm mercury (Hg) or diastolic blood pressure greater than 100 mm Hg)

          -  Currently active diarrhea that may affect the ability of the patient to absorb the
             ZD6474 or tolerate diarrhea

          -  Women who are currently pregnant or breast-feeding

          -  Receipt of any investigational agents within 30 days prior to commencing study
             treatment

          -  Previous enrollment or randomization of treatment in the present study

          -  Major surgery within 4 weeks or incompletely healed surgical incision before starting
             study therapy

          -  Involvement in the planning and conduct of the study (applies to both Astra Zeneca
             staff and staff at the study site)