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:

Completed

Phase:

Phase 2

Trial Eligibility

Document

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

  • ORG STUDY ID: 11-0265
  • SECONDARY ID: NCI-2011-01246
  • NCT ID: NCT01414426

Conditions

  • Lip and Oral Cavity Squamous Cell Carcinoma
  • Oral Cavity Verrucous Carcinoma
  • Precancerous Condition

Interventions

DrugSynonymsArms
vandetanibAZD6474, ZD6474Arm I (chemoprevention)

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

NameTypeDescriptionInterventions
Arm I (chemoprevention)ExperimentalPatients receive vandetanib PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.
  • vandetanib
Arm II (placebo)Placebo ComparatorPatients 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)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Comparison Between Treatment Groups of the Within-patient Change in MVD Score Following Treatment Initiation
    Time Frame:Baseline to 3 months
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure:Number of Participants With Adverse Events
    Time Frame:Weekly during treatment, up to week 24
    Safety Issue:
    Description:Adverse events rate shows the total number of subjects with an AE.
    Measure:Number of Participants Who Adhered to Treatment
    Time Frame:Over 6 months
    Safety Issue:
    Description:Number of participants who Adhered to Treatment
    Measure:Development of Oral and Other Cancers
    Time Frame:At 6, 9, and 12 months and then ever 6 months for 2 years
    Safety Issue:
    Description:Number of patients with new cancer
    Measure:Biologic Effect of EGFR and VEGFR2 Inhibition
    Time Frame:Baseline and 3 and 6 months
    Safety Issue:
    Description:Effect of treatment on EGFR and VEGFR2 inhibition

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Completed
    Lead Sponsor:University of Chicago

    Last Updated

    January 14, 2021