S0636: Erlotinib and Bevacizumab in Never-Smokers With Stage IIIB or Stage IV Primary Non-Small Cell Lung Cancer

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 also may stop the growth of non-small cell lung cancer 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 IIIB or stage IV primary non-small cell lung cancer who have never smoked.

Detailed Description
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OBJECTIVES: Primary Assess overall survival of patients with stage IIIB or IV primary non-small cell lung adenocarcinoma who have never smoked and are treated with erlotinib hydrochloride and bevacizumab. Secondary Assess progression-free survival of patients treated with this regimen. Assess the response rate (confirmed and unconfirmed, complete and partial) in a subset of patients with measurable disease treated with this regimen. Evaluate the frequency and severity of toxicities associated with this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral erlotinib hydrochloride 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 periodically for up to 3 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 Never-Smokers With Stage IIIB and IV Primary NSCLC Adenocarcinomas

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: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Adenocarcinoma No component of squamous cell carcinoma present Incompletely resected or unresectable disease Stage IIIB or IV disease as defined below: Selected 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 lung cancer in a separate lobe after resection or radiotherapy within the past 5 years OR multifocal lesions in > 1 lobe considered stage IV disease New lesions occurring ≥ 5 years after resection may be considered a separate primary cancer and are not allowed if this is the only focus of lung cancer Measurable and/or nonmeasurable disease by CT scan, positron emission tomography scan, or MRI Disease must be present outside a previous radiotherapy field OR a new lesion must be inside the port Measurable disease must be assessed within the past 28 days Nonmeasurable disease must be assessed within the past 42 days Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease Must be a lifelong nonsmoker (< 100 cigarettes in lifetime) 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/mm^3 Platelet count ≥ 100,000/mm^3 Total bilirubin normal SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present) Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases present) Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Hypertension allowed if controlled on medication prior to study enrollment Must be willing to provide prior smoking history No immediate life-threatening complications from malignancies No prior major medical condition, psychological condition, or social situation that would preclude study treatment 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 either thrombosis or hemorrhage, including hemorrhagic or thrombotic stroke, or other CNS bleeding No serious nonhealing wound, ulcer, or bone fracture No other prior malignancy except for the following: Adequately treated basal cell or squamous cell skin cancer Adequately treated stage I or II cancer from which the patient is currently in complete remission In situ cervical cancer Any other cancer from which the patient has been disease-free for 5 years PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 7 days since prior fine-needle aspiration or core biopsy At least 28 days since prior radiotherapy (14 days for palliative radiotherapy) and recovered At least 28 days since prior surgery (e.g., thoracic or other major surgeries) and recovered At least 28 days since prior systemic chemotherapy Prior biologic therapy allowed No prior gefitinib, erlotinib hydrochloride, bevacizumab, or other targeted therapies against the epidermal growth factor receptor or vascular endothelial growth factor axes Concurrent stable, therapeutic anticoagulation therapy allowed (e.g., 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 concurrent surgery No other concurrent nonprotocol treatment (including chemotherapy, hormonal therapy, biological therapy, or radiotherapy) directed at this cancer

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 date of death due to any cause. Patients last known to be alive are censored at date of last contact. | Disease assessment is performed every 6 weeks for 18 weeks, then every 9-12 weeks until progression up to 2 years. After disease progression, patients must be followed every 3 months for 1 year and then every 6 months for a maximum of 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.0), as a 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, or unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided) or appearance of any new lesion/site, or death due to disease without prior documentation of progression and without symptomatic deterioration. | Disease assessment is performed every 6 weeks for 18 weeks, then every 9-12 weeks until progression up to 2 years. After disease progression, patients must be followed every 3 months for 1 year and then every 6 months for a maximum of 3 years. | 
| Response Rate (Complete and Partial) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline. | Disease assessment is performed every 6 weeks for 18 weeks, then every 9-12 weeks until progression up to 2 years. After disease progression, patients must be followed every 3 months for 1 year and then every 6 months for a maximum of 3 years. | 
| Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. | Toxicity assessment was evaluated after each cycle (21 days) while on protocol therapy. | 

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