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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00257608
First received: November 21, 2005
Last updated: March 18, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: bevacizumab
Drug: placebo
Drug: erlotinib HCl
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Any Adverse Events During Post-Chemotherapy Phase [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
    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.

  • Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008).

  • Incidence of Study Treatment Discontinuation [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
    Overall survival was defined as the length of time from randomization to death.


Enrollment: 1145
Study Start Date: January 2006
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab
Intravenous repeating dose
Drug: erlotinib HCl
Oral repeating dose
Placebo Comparator: 2 Drug: bevacizumab
Intravenous repeating dose
Drug: placebo
Oral repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00257608

  Show 247 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Donald Strickland, M.D. Genentech, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00257608     History of Changes
Other Study ID Numbers: AVF3671g  BO20800 
Study First Received: November 21, 2005
Results First Received: November 9, 2015
Last Updated: March 18, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
NSCLC
Lung Cancer
ATLAS
Avastin
Tarceva

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bevacizumab
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 03, 2016