Head and Neck Cancer, Precancerous Condition
Conditions
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
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.
Interventions
BIOLOGICALcetuximab
given IV
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Based on Histologic Grade | 8 weeks | Histologic downgrade by at least one grade of dysplasia (e.g Severe to Moderate). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Based on Clinical Assessment | 8 weeks | Clinical visualization on whether lesion responded to treatment (i.e., direct visualization of the lesion combined with histologic grade) |
| 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 | — |
Countries
Canada, United States
Participant flow
Recruitment details
Study enrolled patients with premalignant lesions of the Head and Neck with mild, moderate or severe dysplasias
Pre-assignment details
16 participants did not have biopsy proven dysplasia as required by protocol and were not randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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.
cetuximab: given IV | 13 |
| Arm II (Control) Patients receive regular follow-up care | 6 |
| Total | 19 |
Baseline characteristics
| Characteristic | Arm I (Treatment) | Arm II (Control) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 4 Participants | 12 Participants |
| Region of Enrollment United States | 13 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 6 |
| other Total, other adverse events | 0 / 13 | 0 / 6 |
| serious Total, serious adverse events | 0 / 13 | 0 / 6 |
Outcome results
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).
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Treatment) | Number of Participants With Objective Response Based on Histologic Grade | 13 Participants |
| Arm II (Control) | Number of Participants With Objective Response Based on Histologic Grade | 6 Participants |
Secondary
Lesion Recurrence
Time frame: Up to year 5 years post-treatment
Population: No patients were followed for this outcome measure
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)
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Treatment) | Number of Participants With Objective Response Based on Clinical Assessment | 13 Participants |
| Arm II (Control) | Number of Participants With Objective Response Based on Clinical Assessment | 6 Participants |
Secondary
Status of EGFR Pathway Components and Molecular Alterations in Post-treatment Biopsies
Time frame: At 8 weeks post-treatment
Population: Data was not collected for this outcome
Secondary
Status of Epidermal Growth Factor Receptor (EGFR) Pathway Components and Molecular Alterations in Pre-treatment Biopsies
Time frame: Baseline (pre-treatment)
Population: Data was not collected for this outcome
Secondary
Survival
Time frame: Up to year 5 years post-treatment
Population: No patients were followed for this outcome measure