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

NCT00524017 | Completed Phase 2 Results DMC

• 5 other identifiers: J0644 CDR0000562250P50CA096784P30CA006973JHOC-J0644JHOC-NA_00001757
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 10

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.

Conditions

Head and Neck Cancer; Precancerous Condition

Keywords

hypopharyngeal cancer; laryngeal cancer; lip and oral cavity cancer; nasopharyngeal cancer; oropharyngeal cancer; paranasal sinus and nasal cavity cancer; salivary gland cancer; precancerous condition

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of Participants With Objective Response Based on Clinical Assessment

  8 weeks

• Status of Epidermal Growth Factor Receptor (EGFR) Pathway Components and Molecular Alterations in Pre-treatment Biopsies

  Baseline (pre-treatment)

• Status of EGFR Pathway Components and Molecular Alterations in Post-treatment Biopsies

  At 8 weeks post-treatment

• Survival

  Up to year 5 years post-treatment

• Lesion Recurrence

  Up to year 5 years post-treatment

Study Arms (2)

Arm I (treatment)

EXPERIMENTAL

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.

Biological: cetuximab

Arm II (control)

NO INTERVENTION

Patients receive regular follow-up care

Interventions

cetuximab BIOLOGICAL

given IV

Arm I (treatment)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10010, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Precancerous Conditions; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Nasopharyngeal Neoplasms; Oropharyngeal Neoplasms; Salivary Gland Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Mouth Diseases; Nasopharyngeal Diseases; Salivary Gland Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Zubair Khan
• Organization: SKCCC

zkhan@jhmi.edu

4109553157

Study Officials

• Joseph Califano, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 12, 2020
• Results First Posted: March 12, 2020

Record last verified: 2020-02

Locations

US (9); CA (1)