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

• ClinicalTrials.gov Identifier: NCT00257608
• Recruitment Status: Completed
• First Posted: November 23, 2005
• Results First Posted: March 15, 2016
• Last Update Posted: April 18, 2016
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: November 21, 2005
• First Posted Date: November 23, 2005
• Results First Submitted Date: November 9, 2015
• Results First Posted Date: March 15, 2016
• Last Update Posted Date: April 18, 2016
• Study Start Date: January 2006
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 16, 2016)

Progression-free Survival (PFS) [ Time Frame: Approximately 3 years ]

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.

• Original Primary Outcome Measures (submitted: November 21, 2005): To compare progression free survival (PFS) in subjects randomized to bevacizumab+erlotinib versus bevacizumab+erlotinib placebo in subjects with non squamous non-small cell lung cancer (NSCLC).

Current Secondary Outcome Measures (submitted: March 18, 2016)

• Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase [ Time Frame: Approximately 3 years ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  Overall survival was defined as the length of time from randomization to death.

• Original Secondary Outcome Measures (submitted: November 21, 2005): To evaluate the safety of bevacizumab during the chemotherapy phase by chemotherapy regimen and overall; to evaluate the safety of bevacizumab+erlotinib versus bevacizumab+erlotinib-placebo.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Comparing Bevacizumab Therapy With or Without Erlotinib for First-Line Treatment of Non-Small Cell Lung Cancer (ATLAS)
• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: bevacizumab
  Intravenous repeating dose
• Drug: placebo
  Oral repeating dose
• Drug: erlotinib HCl
  Oral repeating dose

Study Arms

• Experimental: 1
  Interventions:

  • Drug: bevacizumab
  • Drug: erlotinib HCl
• Placebo Comparator: 2
  Interventions:

  • Drug: bevacizumab
  • Drug: placebo

• Publications *: Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C, Miller V. ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2013 Nov 1;31(31):3926-34. doi: 10.1200/JCO.2012.47.3983. Epub 2013 Oct 7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 10, 2012): 1145
• Original Enrollment (submitted: November 21, 2005): 1150
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Bulgaria, Hong Kong, Israel, Italy, Mexico, Philippines, Romania, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT00257608
• Other Study ID Numbers: AVF3671g; BO20800 ( Other Identifier: Hoffmann-La Roche )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Donald Strickland, M.D.; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: March 2016