Trastuzumab in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer That Overexpresses HER2

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of trastuzumab in treating patients who have stage IIIB or stage IV non-small cell lung cancer that overexpresses HER2. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the activity of trastuzumab (Herceptin) in patients with stage IIIB or IV HER2-overexpressing non-small cell lung cancer. SECONDARY OBJECTIVES: I. Determine the duration of response in patients treated with this regimen. II. Determine the toxicity of this treatment regimen in this patient population. III. Assess levels of circulating HER2 and correlate with HER2 expression in this patient population. V. Correlate circulating HER2 levels with non-small cell lung cancer tissue HER2 expression. OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Treatment continues once a week in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression or death. PROJECTED ACCRUAL: Approximately 84 patients (42 per stratum) will be accrued for this study within 17.5 months.

Official Title
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A Phase II Trial of Trastuzumab (Herceptin) for Advanced Stage (IIIB, IV), HER2 Overexpressing, Non-Small Cell Lung Cancer

Conditions
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Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage IIIB or IV non-small cell lung cancer Supraclavicular node involvement allowed Malignant pleural effusion allowed (cytological confirmation not required if pleural fluid bloody or exudative) No stage IIIB patients eligible for CLB protocols comprising combined chemotherapy and chest radiotherapy Recurrent disease allowed HER2 overexpression (2-3+) At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques At least 10 mm by spiral CT scan The following are not considered measurable: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses not confirmed and followed by imaging Cystic lesions No CNS metastases Performance status - ECOG 0-2 Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) Creatinine no greater than 1.5 times ULN LVEF at least 45% (by echocardiogram or MUGA) Not pregnant or nursing Fertile patients must use effective contraception HIV negative No concurrent immunologic disease (e.g., autoimmune disease) No history of allergy to murine products No prior murine antibodies No prior anthracyclines No more than 1 prior chemotherapy regimen for lung cancer At least 4 weeks since prior chemotherapy No concurrent chemotherapy No concurrent steroids except for adrenal failure or dexamethasone as an antiemetic No concurrent hormonal therapy except for nondisease-related conditions (e.g., insulin for diabetes) At least 6 months since prior radiotherapy No concurrent palliative radiotherapy At least 4 weeks since prior major surgery

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: Treatment (trastuzumab)<br>Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Treatment continues once a week in the absence of disease progression or unacceptable toxicity. | Biological: trastuzumab<br>* Given IV<br>* Other names: MOAB HER2;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete response [CR] and partial response [PR]) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Kaplan-Meier curves will be used to describe OS. | From registration until death or last known follow-up, assessed up to 5 years | 
| Failure-free survival (FFS) | Kaplan-Meier curves will be used to describe FFS. | Time between registration and disease progression, death, or last known follow-up, assessed up to 5 years | 
| Duration of response | Kaplan-Meier curves will be used to describe duration of response. | Time between the initial documentation of response and subsequent failure (death, disease progression), assessed up to 5 years | 
| Toxicity as assessed by NCI's Common Toxicity Criteria | The frequency of occurrence of various toxicities will be tabulated by the most severe occurrence experienced by each individual patient. | Up to 5 years | 
| Relationship between HER2 expression in tumor tissue and serum | A 95% confidence interval for this proportion will be estimated using the binomial distribution. The level of circulating HER2 receptor will be descriptively summarized with means, medians, quartiles, etc. | Up to 5 years |