Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01414426
Other study ID # 11-0265
Secondary ID NCI-2011-01246
Status Completed
Phase Phase 2
First received
Last updated
Start date January 2012
Est. completion date June 1, 2019

Study information

Verified date January 2021
Source University of Chicago
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date June 1, 2019
Est. primary completion date January 1, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
vandetanib
Given PO
Other:
placebo
Given PO
immunohistochemistry staining method
Correlative studies
laboratory biomarker analysis
Correlative studies
Procedure:
biopsy
Correlative studies
Other:
pharmacological study
Correlative studies

Locations

Country Name City State
United States University of Chicago Chicago Illinois

Sponsors (2)

Lead Sponsor Collaborator
University of Chicago National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Baseline to 3 months
Secondary Number of Participants With Adverse Events Adverse events rate shows the total number of subjects with an AE. Weekly during treatment, up to week 24
Secondary Number of Participants Who Adhered to Treatment Number of participants who Adhered to Treatment Over 6 months
Secondary Development of Oral and Other Cancers Number of patients with new cancer At 6, 9, and 12 months and then ever 6 months for 2 years
Secondary Biologic Effect of EGFR and VEGFR2 Inhibition Effect of treatment on EGFR and VEGFR2 inhibition Baseline and 3 and 6 months
See also
  Status Clinical Trial Phase
Completed NCT01946217 - Factors Affecting Patient Participation in AIDS Malignancy Clinical Trials Consortium Clinical Trials N/A
Completed NCT00550589 - Cidofovir in Treating HIV-Infected Patients With High-Grade Squamous Intraepithelial Lesions of the Skin Near the Anus Phase 2
Completed NCT00653146 - The Effects of MBSR in Improving Immune Response to Human Papillomavirus in Patients With Cervical Dysplasia N/A
Terminated NCT00629577 - Gene Expression Profiling of Cervical Cancer Progression in Biopsies and Tissue Samples Phase 1
Completed NCT00103246 - Photodynamic Therapy Using Silicon Phthalocyanine 4 in Treating Patients With Actinic Keratosis, Bowen's Disease, Skin Cancer, or Stage I or Stage II Mycosis Fungoides Phase 1
Completed NCT00066430 - Infrared Coagulation in Preventing Anal Cancer in Patients With HIV Who Have Anal Neoplasia Phase 1
Completed NCT00522197 - ACAPHA in Preventing Lung Cancer in Former Smokers With Bronchial Intraepithelial Neoplasia Phase 2
Completed NCT00003384 - Protein Expression as a Potential Diagnostic Biomarker of Cervical Dysplasia and/or Cancer N/A
Terminated NCT02574442 - Pilot Study In Vivo Confocal Microscopy Probe for Cervical Precancer
Completed NCT00719563 - American Ginseng in Treating Patients With Fatigue Caused by Cancer Phase 3
Terminated NCT00899951 - Studying Fentanyl in Patients With Cancer N/A
Completed NCT00873288 - Activating Collaborative CIS Support Via Targeted Provider Mailing N/A
Terminated NCT00611650 - Green Tea Extract in Treating Current or Former Smokers With Bronchial Dysplasia Phase 2
Completed NCT00462813 - Diindolylmethane in Treating Patients With Abnormal Cervical Cells Phase 3
Completed NCT00006348 - Ondansetron in Treating Patients With Advanced Cancer and Chronic Nausea and Vomiting Not Caused by Cancer Treatment Phase 3
Completed NCT00666731 - Breast Cancer Registry for Participants With Breast Cancer or Characteristics of Hereditary Breast Cancer
Recruiting NCT04445532 - Hepatobiliary Tumors Tissue Samples Acquisition
Completed NCT00685568 - Celecoxib in Preventing Colorectal Cancer in Young Patients With a Genetic Predisposition for Familial Adenomatous Polyposis Phase 1
Terminated NCT00942422 - Green Tea Extract in Treating Patients With Monoclonal Gammopathy of Undetermined Significance and/or Smoldering Multiple Myeloma Phase 2
Completed NCT00788164 - Vaccine Therapy With or Without Imiquimod in Treating Patients With Grade 3 Cervical Intraepithelial Neoplasia Phase 1