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

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ClinicalTrials.gov Identifier: NCT00524017
Recruitment Status : Completed
First Posted : September 3, 2007
Last Update Posted : January 31, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE August 31, 2007
First Posted Date  ICMJE September 3, 2007
Last Update Posted Date January 31, 2012
Study Start Date  ICMJE May 2007
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2011)
Objective response based on histologic grade [ Time Frame: End of Treatment of Observation ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 31, 2007)
Objective response based on histologic grade
Change History Complete list of historical versions of study NCT00524017 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2011)
  • Objective response based on clinical assessment (i.e., direct visualization of the lesion combined with histologic grade) [ Time Frame: End of Treatment of Observation ]
  • Status of EGFR pathway components and molecular alterations in pre- and post-treatment biopsies [ Time Frame: End of Treatment of Observation ]
  • Survival and lesion recurrence [ Time Frame: Up to year 5 after Treatment on Trial ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2007)
  • Objective response based on clinical assessment (i.e., direct visualization of the lesion combined with histologic grade)
  • Status of EGFR pathway components and molecular alterations in pre- and post-treatment biopsies
  • Survival and lesion recurrence
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cetuximab in Treating Patients With Precancerous Lesions of the Upper Aerodigestive Tract
Official Title  ICMJE Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions
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 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Head and Neck Cancer
  • Precancerous Condition
Intervention  ICMJE
  • Biological: cetuximab
    given IV
  • Procedure: standard follow-up care
    Patients receive regular follow-up care
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Biological: cetuximab
  • No Intervention: Arm II (control)
    Patients receive regular follow-up care
    Intervention: Procedure: standard follow-up care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 27, 2012)
35
Original Enrollment  ICMJE
 (submitted: August 31, 2007)
60
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  • ECOG performance status 0-1
  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00524017
Other Study ID Numbers  ICMJE J0644 CDR0000562250
P50CA096784 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0644
JHOC-NA_00001757
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Joseph Califano, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP