A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a Phase III, multicenter, placebo-controlled, double-blind, randomized study. Approximately 650 patients will be randomized in a 1:1 ratio to one of two treatment arms.

Official Title
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A Phase III, Multicenter, Placebo-Controlled, Double-Blind, Randomized Clinical Trial to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva (Erlotinib) Compared With Tarceva Alone for Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) After Failure of Standard First-Line Chemotherapy

Conditions
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Non-Small Cell Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Cytologically or histologically confirmed NSCLC Clinical or radiographic progression during or after first-line chemotherapy or chemoradiotherapy for NSCLC Consent to provide archival tissue for analysis is required for participation in this study Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Age ≥ 18 years Use of an acceptable means of contraception for men and women of childbearing potential International normalized ratio (INR) no greater than 1.3 and an aPTT no greater than the upper limits of normal within 28 days prior to enrollment for patients not on low-molecular-weight heparin or fondaparinux Exclusion Criteria: Squamous cell carcinoma Prior treatment with an investigational or marketed inhibitor of the Epidermal Growth Factor Receptor (EGFR) pathway or anti-angiogenesis agent Systemic chemotherapy, radiotherapy, or investigational treatment within 28 days prior to randomization Local palliative radiotherapy within 14 days prior to randomization or persistent adverse effects from radiotherapy that have not resolved to Grade 2 or less following completion of treatment Whole brain radiotherapy or stereotactic radiosurgery for brain metastases within 4 weeks of Day 0 Neurosurgery for brain metastases within 24 weeks of Day 0 Brain biopsy within 12 weeks of Day 0 Current use of dexamethasone for treatment associated with brain metastases History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation History of any of the following within 6 months prior to Day 0: serious systemic disease, uncontrolled hypertension, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months Progressive neurologic symptoms in patients with a history of brain metastases Full-dose anticoagulation with warfarin Chronic daily use of aspirin or other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization Anticipation of need for a major surgical procedure during the course of the study Serious, non-healing wound, ulcer, or bone fracture Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption Pregnancy or breast-feeding Presence of another invasive cancer within 5 years prior to randomization Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or their ability to comply with study requirements

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: erlotinib HCl + bevacizumab<br>oral erlotinib HCl 150 mg/day orally + intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle | Drug: bevacizumab<br>* intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle<br>|
| Placebo Comparator: erlotinib HCl + placebo<br>oral erlotinib HCl 150 mg/day orally + intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle | Drug: erlotinib HCl<br>* oral erlotinib HCl 150 mg/day orally<br>Drug: placebo<br>* intravenous infusion of placebo at a dose of 15 mg/kg on the first day of each 3-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Among All Randomized Patients | Overall Survival was defined as the period from the date of randomization until the date of patient death from any cause. For patients who had not died, survival data was censored at the date of last contact. | From the date of randomization until the date of patient death from any cause, or the date of last contact. (Up to 3.1 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the time from randomization to documented disease progression, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), or death on study treatment, whichever occurred first. | From randomization to documented disease progression or death on study treatment, whichever occurred first. (Up to 3.1 years) | 
| Percentage of Participants With Objective Response | Objective response was defined as a complete or partial response determined by RECIST on two consecutive occasions >= 4 weeks apart. | The median duration of Objective response was up to 9.7 months | 
| Duration of Objective Response | Duration of objective response was defined as the period from the date of the initial partial or complete response until the date of disease progression or death on study treatment from any cause. For patients who had not died, data was censored at the date of last contact. | Period from Objective response until disease progression or death on study treatment. (Up to 29.5 months) | 

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