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

NCT01414426 | Completed Phase 2 Results

• 2 other identifiers: 11-0265NCI-2011-01246
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Participants With Adverse Events

  Weekly during treatment, up to week 24

• Number of Participants Who Adhered to Treatment

  Over 6 months

• Development of Oral and Other Cancers

  At 6, 9, and 12 months and then ever 6 months for 2 years

• Biologic Effect of EGFR and VEGFR2 Inhibition

  Baseline and 3 and 6 months

Study Arms (2)

Arm I (chemoprevention)

EXPERIMENTAL

Patients receive vandetanib PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: vandetanib; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy; Other: pharmacological study

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

Other: placebo; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy; Other: pharmacological study

Interventions

vandetanib DRUG

Given PO

Also known as: AZD6474, ZD6474

Arm I (chemoprevention)

placebo OTHER

Given PO

Also known as: PLCB

Arm II (placebo)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I (chemoprevention); Arm II (placebo)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (chemoprevention); Arm II (placebo)

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Arm I (chemoprevention); Arm II (placebo)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I (chemoprevention); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Lymphoid Interstitial Pneumonia; Squamous Cell Carcinoma of Head and Neck; Precancerous Conditions

Interventions

vandetanib; Immunohistochemistry; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Alexander Pearson
• Organization: UChicago

apearson5@medicine.bsd.uchicago.edu

855-702-8222

Study Officials

• Tanguy Seiwert, M.D.

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2011
• First Posted: August 11, 2011
• Study Start: January 1, 2012
• Primary Completion: January 1, 2019
• Study Completion: June 1, 2019
• Last Updated: January 14, 2021
• Results First Posted: January 14, 2021

Record last verified: 2021-01

Locations

US (1)