Clinical trial NCT00130728: A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: NSCLC
Avastin
Tarceva
Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2005-08-16
Enrollment: 636
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Overall Survival (OS) Among All Randomized Patients
timeFrame: 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 outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization to documented disease progression or death on study treatment, whichever occurred first. (Up to 3.1 years)
measure: Percentage of Participants With Objective Response
timeFrame: The median duration of Objective response was up to 9.7 months
measure: Duration of Objective Response
timeFrame: Period from Objective response until disease progression or death on study treatment. (Up to 29.5 months)
Other outcomes:
Locations:
city: Vallejo
country: United States
facility: Kaiser Permanente - Vallejo
state: California
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC; Research
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Annapolis
country: United States
facility: Anne Arundel Health System Research Instit-Annapolis Oncology Ctr
state: Maryland
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. doi: 10.1016/S0140-6736(11)60545-X.