Clinical Trials /

Vandetanib in Preventing Head and Neck Cancer in Patients With Precancerous Head and Neck Lesions

NCT01414426

Description:

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

Related Conditions:
  • Oral Cavity Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Vandetanib in Preventing Head and Neck Cancer in Patients With Precancerous Head and Neck Lesions

Title

  • Brief Title: Vandetanib in Preventing Head and Neck Cancer in Patients With Precancerous Head and Neck Lesions
  • Official Title: Randomized Placebo- Controlled Pilot Study of ZD6474 as a Chemopreventive Agent for Premalignant Lesions of the Head and Neck
  • Clinical Trial IDs

    NCT ID: NCT01414426

    ORG ID: 11-0265

    NCI ID: NCI-2011-01246

    Trial Conditions

    Lip and Oral Cavity Squamous Cell Carcinoma

    Oral Cavity Verrucous Carcinoma

    Precancerous Condition

    Trial Interventions

    Drug Synonyms Arms
    vandetanib AZD6474, ZD6474 Arm I (chemoprevention)

    Trial Purpose

    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

    Detailed Description

    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.

    Trial Arms

    Name Type Description Interventions
    Arm I (chemoprevention) Experimental Patients receive vandetanib PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. vandetanib
    Arm II (placebo) Placebo Comparator Patients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

    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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Comparison between treatment groups of the within-patient change in MVD score following treatment initiation

    Secondary Outcome Measures

    Adverse events rate

    Adherence to treatment

    Development of oral and other cancers

    Biologic effect of EGFR and VEGFR2 inhibition

    Trial Keywords