Cetuximab in Treating Patients With Precancerous Lesions of the Upper Aerodigestive Tract

NCT ID: NCT00524017

Last Updated: 2020-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2011-12-31

Brief Summary

RATIONALE: Monoclonal antibodies, such as cetuximab, can block abnormal cell growth in different ways. Some block the ability of abnormal cells to grow and spread. Others find abnormal cells and help kill them or carry cell-killing substances to them.

PURPOSE: This randomized phase II trial is studying how well cetuximab works in treating patients with precancerous lesions of the upper aerodigestive tract.

Detailed Description

OBJECTIVES:

Primary

• To determine the histologic response rate in patients with high-risk, premalignant lesions of the upper aerodigestive tract treated with cetuximab.

Secondary

• To determine the clinical response rate in these patients.
• To determine if patterns of epidermal growth factor receptor (EGFR) component expression are altered in these patients.
• To determine the change in status of genetic alterations, including loss of heterozygosity, in these patients.

OUTLINE: This is a multicenter study. Patients are stratified by lesion type [diffuse dysplasia vs recurrent dysplasia vs dysplastic lesions with 3p or 9p loss of heterozygosity (LOH)]. Patients are randomized to 1 of 2 arms.

• Arm I (treatment): Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity.
• Arm II (control): Patients receive regular follow-up care. Patients have the option of receiving cetuximab after completion of the study.

In both arms, patients with persistent or recurrent high-grade dysplasia or dysplastic lesions with 3p or 9p LOH undergo surgical resection, if feasible, after week 8.

Tumor biopsy samples are obtained at baseline* and after week 8 for histologic and biomarker correlative studies. Tissue samples are analyzed by histopathology to determine histologic changes in post-treatment lesions and by immuno-histochemistry (IHC) to measure expression and activation of EGFR signaling pathway components. LOH studies are also performed.

NOTE: *Paraffin-embedded tissue from the original diagnostic biopsy may be used for baseline assessment, if the diagnostic biopsy was performed within 3 months prior to study entry.

After completion of study therapy, patients are followed at approximately 1 month, every 3 months for 2 years, and then every 6 months for up to 5 years as per routine standard of care.

Conditions

Head and Neck Cancer; Precancerous Condition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm I (treatment)

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

given IV

Arm II (control)

Patients receive regular follow-up care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

cetuximab

given IV

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• No evidence of clinically active interstitial lung disease

• Patients with chronic, stable radiographic changes who are asymptomatic are eligible
• No history or radiological evidence of pulmonary fibrosis
• No acute myocardial infarction within the past 3 months
• No uncontrolled angina, arrhythmia, or congestive heart failure
• No evidence of other severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
• No evidence of any other significant clinical disorder or laboratory finding that would preclude study participation
• No known severe hypersensitivity to cetuximab or any of its excipients
• No prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy
• No severe abnormality of the cornea

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior oncologic or other major surgery or biopsy
• More than 30 days since prior non-approved or investigational drugs
• No prior chemotherapy, radiotherapy, or surgery for the premalignant lesions
• No prior EGFR-targeted agents (e.g., cetuximab, gefitinib, or erlotinib)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Califano, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Countries

United States; Canada

Other Identifiers

P50CA096784

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0644

Identifier Type: -

Identifier Source: secondary_id

JHOC-NA_00001757

Identifier Type: -

Identifier Source: secondary_id

J0644 CDR0000562250

Identifier Type: -

Identifier Source: org_study_id