A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: bevacizumab; erlotinib HCl; placebo
Intervention description: intravenous infusion of bevacizumab at a dose of 15 mg/kg on the first day of each 3-week cycle; 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
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 636.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC; Avastin; Tarceva; Lung Cancer

Summary:

      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.
    

Eligibility criteria:

        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