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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00524017
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 35
• Locations: 10
• Arms: 2
• Duration (Months): 55
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Precancerous Condition	Biological: cetuximab	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: cetuximab; given IV
No Intervention: Arm II (control) Patients receive regular follow-up care

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

2. Status of Epidermal Growth Factor Receptor (EGFR) Pathway Components and Molecular Alterations in Pre-treatment Biopsies [Baseline (pre-treatment)]

3. Status of EGFR Pathway Components and Molecular Alterations in Post-treatment Biopsies [At 8 weeks post-treatment]

4. Survival [Up to year 5 years post-treatment]

5. Lesion Recurrence [Up to year 5 years post-treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
2	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
3	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
4	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
5	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
6	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
7	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10010
8	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
9	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
10	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6

Sponsors and Collaborators

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

Investigators

• Study Chair: Joseph Califano, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00524017
• Other Study ID Numbers: J0644 CDR0000562250; P50CA096784; P30CA006973; JHOC-J0644; JHOC-NA_00001757
• First Posted: Sep 3, 2007
• Last Update Posted: Mar 12, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: hypopharyngeal cancer; laryngeal cancer; lip and oral cavity cancer; nasopharyngeal cancer; oropharyngeal cancer; paranasal sinus and nasal cavity cancer; salivary gland cancer; precancerous condition
• Additional relevant MeSH terms: Precancerous Conditions; Cetuximab

Study Results

Participant Flow

Recruitment Details	Study enrolled patients with premalignant lesions of the Head and Neck with mild, moderate or severe dysplasias
Pre-assignment Detail	16 participants did not have biopsy proven dysplasia as required by protocol and were not randomized to treatment.

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Period Title: Overall Study
STARTED	13	6
COMPLETED	13	5
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Arm I (Treatment)	Arm II (Control)	Total
Arm/Group Description	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	Patients receive regular follow-up care	Total of all reporting groups
Overall Participants	13	6	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 61.5%	4 66.7%	12 63.2%
>=65 years	5 38.5%	2 33.3%	7 36.8%
Sex: Female, Male (Count of Participants)
Female	6 46.2%	1 16.7%	7 36.8%
Male	7 53.8%	5 83.3%	12 63.2%
Region of Enrollment (Count of Participants)
United States	13 100%	6 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response Based on Histologic Grade
Description	Histologic downgrade by at least one grade of dysplasia (e.g Severe to Moderate).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Measure Participants	13	6
Count of Participants [Participants]	13 100%	6 100%

2. Secondary Outcome

Title	Number of Participants With Objective Response Based on Clinical Assessment
Description	Clinical visualization on whether lesion responded to treatment (i.e., direct visualization of the lesion combined with histologic grade)
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Measure Participants	13	6
Count of Participants [Participants]	13 100%	6 100%

3. Secondary Outcome

Title	Status of Epidermal Growth Factor Receptor (EGFR) Pathway Components and Molecular Alterations in Pre-treatment Biopsies
Time Frame	Baseline (pre-treatment)

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Measure Participants	0	0

4. Secondary Outcome

Title	Status of EGFR Pathway Components and Molecular Alterations in Post-treatment Biopsies
Time Frame	At 8 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Measure Participants	0	0

5. Secondary Outcome

Title	Survival
Time Frame	Up to year 5 years post-treatment

Outcome Measure Data

Analysis Population Description

No patients were followed for this outcome measure

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Measure Participants	0	0

6. Secondary Outcome

Title	Lesion Recurrence
Time Frame	Up to year 5 years post-treatment

Outcome Measure Data

Analysis Population Description

No patients were followed for this outcome measure

Arm/Group Title	Arm I (Treatment)	Arm II (Control)
Arm/Group Description	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	Patients receive regular follow-up care
Measure Participants	0	0

Adverse Events

Arm/Group Title	Arm I (Treatment)		Arm II (Control)
Arm/Group Description	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		Patients receive regular follow-up care
All Cause Mortality
	Arm I (Treatment)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/6 (0%)
Serious Adverse Events
	Arm I (Treatment)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Treatment)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.