A Study Comparing Bevacizumab Therapy With or Without Erlotinib for First-Line Treatment of Non-Small Cell Lung Cancer (ATLAS)

Study Overview
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Brief Summary
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This is a Phase IIIb, multicenter, randomized, placebo-controlled trial to evaluate the safety and efficacy of chemotherapy+bevacizumab followed by bevacizumab+erlotinib versus bevacizumab+erlotinib placebo in subjects with locally advanced or metastatic NSCLC.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase IIIb Trial Comparing Bevacizumab Therapy With or Without Erlotinib After Completion of Chemotherapy With Bevacizumab for the First-Line Treatment of Locally Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: placebo
* Drug: erlotinib HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Histologically or cytologically confirmed NSCLC Advanced NSCLC or recurrent disease INR no greater than 1.3 and aPTT no greater than upper limits of normal (ULN) within 28 days prior to enrollment for subjects not on low molecular weight heparin or fondaparinux. Subjects on low molecular weight heparin or fondaparinux are not required to meet INR or aPTT limits. Chronic full-dose anticoagulation with warfarin is not permitted. 18 years of age or older For women of childbearing potential and sexually active men, use of an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to enrollment and for the duration of the study Exclusion Criteria: Prior systemic chemotherapy in the metastatic setting Treatment with an investigational or marketed agent that acts by either EGFR inhibition or anti-angiogenesis mechanisms Pregnancy or lactation Any other medical condition, including mental illness or substance abuse, deemed by the clinician to be likely to interfere with a subject's ability to provide informed consent, cooperate, and participate in the study, or to interfere with the interpretation of the results Active infection or a fever within 3 days of enrollment Active malignancy other than lung cancer Radiation therapy to sites other than whole brain within 14 days prior to enrollment History of gross hemoptysis within 3 months prior to enrollment Known hypersensitivity to any of the components of cytotoxic chemotherapy combinations, bevacizumab, or tyrosine kinase inhibitors Inadequately controlled hypertension Unstable angina or New York Heart Association Grade II or greater CHF Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment History of myocardial infarction within 6 months prior to enrollment History of stroke within 6 months prior to enrollment Symptomatic peripheral vascular disease within 6 months prior to enrollment Evidence of bleeding diathesis or coagulopathy Serious, non-healing wound, ulcer, or bone fracture Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment; anticipation of need for major surgical procedure during the course of the study Current, recent, or planned participation in an experimental drug study other than this Genentech-sponsored bevacizumab/erlotinib study Progressive neurologic symptoms in subjects with a history of brain metastases History of significant vascular disease (e.g., aortic aneurysm)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: erlotinib HCl<br>* Oral repeating dose<br>|
| Placebo Comparator: 2<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: placebo<br>* Oral repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the length of time from randomization until documented disease progression or death from any cause, whichever occurred earlier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Data presented until cut-off date 18 July 2008. | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Treatment-emergent adverse events were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.. Number of participants who had Grade >=3TEAEs of pulmonary hemorrhage, gastrointestinal (GI) perforation, arterial thromboembolic (ATE) events, proteinuria, congestive heart failure (CHF), and hypertension were presented. Data presented up to data cutoff 18 July 2008. | Approximately 3 years | 
| Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication. Pulmonary hemorrhage, GI perforation, ATE events, proteinuria, CHF, and hypertension were prospectively identified TEAEs of grade >=3. Data presented until cut-off date 28 January 2009. | Approximately 3 years | 
| Number of Participants With Any Adverse Events During Post-Chemotherapy Phase | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event. Data presented up to data cutoff 19 June 2009. | Approximately 3.5 years | 
| Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008). | Approximately 3 years | 
| Incidence of Study Treatment Discontinuation | Participants in post-chemotherapy phase were discontinued from the study for the reasons other than disease progression. Data presented Up to data cutoff 18 July 2008. | Approximately 3 years | 
| Overall Survival | Overall survival was defined as the length of time from randomization to death. | Approximately 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Lung Cancer, ATLAS, Avastin, Tarceva