S0635: Erlotinib and Bevacizumab in Stage IIIB and IV Bronchioloalveolar Carcinoma

Study Overview
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Brief Summary
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RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving erlotinib together with bevacizumab works in treating patients with stage III or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine overall survival of patients with stage IIIB or IV bronchioloalveolar carcinoma (BAC) or adenocarcinoma with BAC features treated with erlotinib hydrochloride and bevacizumab. Secondary Determine the progression-free survival of patients treated with this regimen. Compare, preliminarily, response as assessed by RECIST criteria vs response as assessed by a central computer-assisted image-analysis system in patients with measurable disease treated with this regimen. Assess the frequency and severity of toxicities of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral erlotinib hydrochloride once daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 2 years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Official Title
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A Phase II Trial of the Combination of OSI-774 (ERLOTINIB; NSC-718781) and Bevacizumab (Rhumab VEGF; NSC-704865) in Stage IIIB and IV Bronchioloalveolar Carcinoma (BAC) and Adenocarcinoma With BAC Features (ADENOBAC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Biopsy-proven* bronchioloalveolar carcinoma (BAC) or BAC variants (e.g., adenocarcinoma with BAC features, BAC with invasive adenocarcinoma) meeting the following criteria: Incompletely resected or unresectable disease No component of squamous cell carcinoma Disease staged as 1 of the following: Stage IIIB disease (T4 [cytologically confirmed malignant pleural effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor], any N, M0) Stage IV disease (any T, any N, M1 [distant metastases present]) Recurrent disease in a separate lobe after prior resection within the past 5 years; multifocal lesions in > 1 lobe; or any disease that is recurrent after surgery or radiotherapy is considered stage IV disease Tumor may be multifocal or diffuse NOTE: *Cytology specimens, including bronchial brushing, washings, or fine needle aspiration specimens, alone are not acceptable for diagnosis Measurable or nonmeasurable disease by chest CT scan Pleural effusions, ascites, and laboratory parameters are not acceptable as only evidence of disease Disease must be present outside field of prior radiotherapy OR a new lesion must be inside port Treated brain metastases allowed provided the patient is asymptomatic and do not require steroids PATIENT CHARACTERISTICS: Zubrod performance status 0-2 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Total bilirubin normal AST or AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present) Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases are present) Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1 g by 24-hour urine collection Willing to provide prior smoking history No hemoptysis ≥ ½ teaspoon within the past 28 days No clinical history of pulmonary or upper respiratory hemorrhage > grade 2 within the past 6 months or > grade 1 within the past 28 days No history of thromboses or hemorrhage, including hemorrhagic or thrombotic stroke, or other CNS bleeding No uncontrolled hypertension No serious nonhealing wound, ulcer, or bone fracture No other prior malignancy except for any of the following: Adequately treated basal cell or squamous cell skin cancer In situ cervical cancer Adequately treated stage I or II cancer that is currently in complete remission Any other cancer from which the patient has been disease free for 5 years Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior therapy At least 28 days since prior radiotherapy (14 days for palliative radiotherapy) At least 28 days since prior surgery (thoracic or other major surgeries) More than 7 days since prior fine-needle aspiration or core biopsy At least 28 days since prior systemic chemotherapy or biologic therapy No prior gefitinib hydrochloride, erlotinib hydrochloride, or bevacizumab No other prior anti-epidermal growth factor receptor or anti-vascular endothelial growth factor therapies Concurrent stable, therapeutic anticoagulation therapy allowed (i.e., warfarin or low molecular weight heparin), provided the patient has no history of bleeding complications on anticoagulation or an inability to establish a stable therapeutic regimen for anticoagulation No other concurrent anticancer therapy, including surgery, chemotherapy, hormone therapy, biologic therapy, or radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Erlotinib and Bevacizumab<br> | Biological: bevacizumab<br> <br> Drug: erlotinib hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From date of registration to maximum of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival |  | From date of registration to maximum of 3 years | 
| Response as Assessed by RECIST Criteria vs Central Computer-assisted Image-analysis System in Patients With Measurable Disease | Images for response assessed by the central computer-assisted image-analysis system were never collected. | From date of registration to maximum of 3 years | 
| Frequency and Severity of Toxicities |  | From date of registration to maximum of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, bronchoalveolar cell lung cancer, adenocarcinoma of the lung