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

Head and Neck Cancer Clinical Trial

Official title:

Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00524017
• Other study ID #: J0644 CDR0000562250
• Secondary ID: P50CA096784P30CA
• Status: Completed
• Phase: Phase 2
• Start date: May 2007
• Est. completion date: December 2011

Study information

• Verified date: February 2020
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed high-risk, premalignant lesions of the upper aerodigestive tract, meeting one of the following criteria:

• Unresectable, diffuse high-grade dysplasia, defined as moderate or severe dysplasia that is not assessable by physical examination and/or that cannot be excised by standard surgical techniques

• previously treated HNSCC with persistent or recurrent high grade dysplasia with no evidence of head and neck malignancy for three months prior to enrollment or who have successfully completed therapy for head and neck malignancy more than 3 months prior to enrollment.

• Dysplastic lesions with 3p or 9p loss of heterozygosity

• Disease location amenable to endoscopic biopsy in an outpatient clinical setting or operative biopsy within the routine scheduling and practice of clinical care

• No medical contraindication to biopsy of the target lesion

• Pathology must be reviewed by the Johns Hopkins Hospital Department of Pathology

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Absolute neutrophil count (ANC) > 1,000/mm³

• Platelet count > 75,000/mm³

• Creatinine clearance > 60 mL/min

• Total serum bilirubin < 1.5 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study therapy

• No concurrent illness likely to preclude study therapy or surgical resection

• Patients with a history of a curatively treated malignancy are eligible provided they are disease-free and have a survival prognosis that exceeds 5 years

• 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)

Related Conditions & MeSH terms

• Head and Neck Cancer
• Precancerous Condition
• Precancerous Conditions

Intervention

Biological:
• cetuximab
given IV

Locations

Country	Name	City	State
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
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	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
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	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Objective Response Based on Histologic Grade	Histologic downgrade by at least one grade of dysplasia (e.g Severe to Moderate).	8 weeks
Secondary	Number of Participants With Objective Response Based on Clinical Assessment	Clinical visualization on whether lesion responded to treatment (i.e., direct visualization of the lesion combined with histologic grade)	8 weeks
Secondary	Status of Epidermal Growth Factor Receptor (EGFR) Pathway Components and Molecular Alterations in Pre-treatment Biopsies		Baseline (pre-treatment)
Secondary	Status of EGFR Pathway Components and Molecular Alterations in Post-treatment Biopsies		At 8 weeks post-treatment
Secondary	Survival		Up to year 5 years post-treatment
Secondary	Lesion Recurrence		Up to year 5 years post-treatment