Cetuximab in Treating Patients With Recurrent or Stage IIIB or Stage IV Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with recurrent or stage IIIB or stage IV lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the objective response rate in patients with recurrent or stage IIIB or IV bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features treated with cetuximab. Secondary Determine the overall survival and time to progression in patients treated with this drug. Determine the toxic effects of this drug in these patients. Correlate expression of total and phosphorylated epidermal growth factor receptor (EGFR), total and phosphorylated AKT3, and total and phosphorylated MAPKinase with response in patients treated with this drug. Determine whether the presence of polymorphisms or mutations in the EGFR gene influences response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours once on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. ACTUAL ACCRUAL: A total of 72 patients were accrued for this study.

Official Title
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Phase II Study of C225 (Cetuximab) for the Treatment of Patients With Advanced Bronchioalveolar Carcinoma (BAC) or Adenocarcinoma With BAC Features

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: cetuximab


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Histologically or cytologically confirmed bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features meeting 1 of the following stage criteria: Stage IIIB disease (with pleural or pericardial effusion) Stage IV disease Recurrent disease Measurable disease Tumor tissue available from biopsy Age of 18 and over ECOG performance status of 0-2 Life expectancy greater than 3 months White blood cell (WBC) ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin normal Aspartate aminotransferase (AST) and/or alanine aminotranferease (ALT) ≤ 2.5 times upper limit of normal Creatinine normal OR Creatinine clearance ≥ 60 mL/min No more than 1 prior chemotherapy regimen for advanced BAC More than 3 years since prior chemotherapy for other malignancies At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for this malignancy and recovered HIV-positive patients are eligible provided the following criteria are met: CD4 count ≥ 100/mm^3 Undetectable viral load within the past 3 months Receiving a stable antiretroviral regimen for ≥ 4 weeks before study entry Fertile patients must use effective contraception At least 2 weeks since prior radiotherapy and recovered EXCLUSION CRITERIA: Untreated brain metastases Patients with stable brain metastases ≥ 4 weeks after external beam radiotherapy to the brain are eligible Acute hepatitis Symptomatic congestive heart failure Uncontrolled hypertension Unstable angina pectoris Cardiac arrhythmia Pregnant or nursing Prior allergic reaction to chimerized or murine monoclonal antibody therapy Documented presence of human anti-mouse antibodies Ongoing or active infection Psychiatric illness or social situation that would preclude study compliance Other uncontrolled illness Prior cetuximab Concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) Other prior known epidermal growth factor receptor inhibitors (e.g., gefitinib or erlotinib) Other concurrent investigational agents Other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab<br>Cetuximab was given as a weekly intravenous (IV) infusion (over 60 minutes) at 250 mg/m2 from week 2 onwards after an initial loading dose of 400 mg/m2 (over 120 minutes) on week 1 until disease progression or unacceptable toxicity. The infusion rate of cetuximab could not exceed 5 mL/min. Each cycle will be 28 days in length. To prevent a hypersensitivity reaction, all patients were premedicated with diphenhydramine hydrochloride 50 mg (or an equivalent antihistamine) by IV (over 30-60 minutes) prior to the first dose of cetuximab. Premedication might be administered prior to subsequent doses, but at the investigator's discretion, the dose of diphenhydramine (or a similar agent) was reduced. | Biological: cetuximab<br> <br> * Other names: C225;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (Proportion of Patients With Objective Response) | Response was evaluated using RECIST 1.0 criteria. Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR. | Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as the time from registration to death. | Every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years | 
| Time to Progression | Time to progression is defined as time from study entry until disease progression. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions. | Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years | 
| Overall Survival by Smoking Status | Medians of overall survival by smoking status are reported. | Overall survival assessed every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline | 
| Time to Progression by Smoking Status | Medians of time to progression by smoking status are reported. | Progression assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchioalveolar carcinoma (BAC), adenocarcinoma with BAC features, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer, cetuximab