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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00257608
• Other study ID #: AVF3671g
• Secondary ID: BO20800
• Status: Completed
• Phase: Phase 3
• First received: November 21, 2005
• Last updated: February 16, 2016
• Start date: January 2006
• Est. completion date: November 2014

Study information

• Verified date: February 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1145
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
Argentina	CEMIC	Buenos Aires
Argentina	Hospital Britanico	Buenos Aires
Argentina	Hospital Pirovano	Buenos Aires
Argentina	Hospital Toru	Buenos Aires
Argentina	Centro Oncologico de Cordoba	Cordoba
Argentina	COIR	Mendoza
Argentina	Instituto Medico Privado	Resistencia
Argentina	Clinica Oncologica de Rosario	Rosario
Argentina	ISIS Clinica Especializada	Sante Fe
Australia	Holy Spirit Hospital Northside	Chermside, QLD
Australia	Sunshine Coast Cancer Centre	Nambour, QLD
Australia	Sir Charles Gairdner Hospital	Nedlands, WA
Australia	Burnside War Memorial Hospital	Toorak Gardens, SA
Belgium	Cliniques Univ St Luc	Brussels
Belgium	CHR Citadelle Liege	Liege
Brazil	Instituto Nacional do Cancer	Rio de Janeiro
Brazil	Hospital Das Clinicas	Sao Paulo
Brazil	Instituto de cancer Arnaldo	Sao Paulo
Bulgaria	Regional Oncodispensary	Plovdiv
Bulgaria	Regional Oncodispensary	Rousse
Bulgaria	Regional Oncodispensary	Shoumen
Bulgaria	National Specialized Hospital	Sofia
Bulgaria	Regional Oncodispensary	Sofia
Bulgaria	UMHAT "Queen Joanna"	Sofia
Bulgaria	Regional Oncodispensary	Stara Zagora
Bulgaria	MHAT "St Marina"	Varna
Bulgaria	Regional Oncodispensary	Veliko Tarnovo
Hong Kong	Princess Margaret Hospital	Hong Kong
Hong Kong	Queen Elizabeth Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Tuen Mun Hospital	Hong Kong
Israel	Hadassah Medical Center	Jerusalem
Israel	Sourasky Medical Center	Tel-Aviv
Israel	Sheba Medical Center	Tel-Hashomer
Italy	Azienda Ospedaliera Univ	Genova
Italy	Ist Nazion per Ricerca Cancro	Genova
Italy	Univ degli Studi di Napoli	Napoli
Italy	Azienda Ospedaliera	Parma
Italy	Azienda Osper di Perugia	Perugia
Italy	Divisione Onc Med dell'Azienda	Udine
Mexico	Torre Medica Cristobal Colon	Acapulco
Mexico	Inst Nacional de Cancerologia	Distrito Federal
Mexico	ISSSTE Merida	Merida
Mexico	Hospital de Especialidades	Torreon, Coahuila
Philippines	Perpetual Succour Hospital	Cebu City	Visayas
Philippines	Philippine General Hospital	Manila	Luzon
Philippines	Univ of Santo Tomas Hospital	Manila
Philippines	The Medical City	Pasig City	Luzon
Philippines	St Luke's Medical Center	Quezon City
Philippines	Veterans Memorial Medical Ctr	Quezon City	Luzon
Romania	Centrul de Onc Medical Lasi	Iasi
Romania	Spitalul Clinic Judetean Sibiu	Sibiu
Romania	Spitalul Judetean de Urgente	Suceava
Singapore	National Cancer Center	Singapore
Spain	Hospital de Cruces	Barakaldo
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario	La Laguna
Spain	Corporacio Sanitaria Parc	Sabadell	Barcelona
Spain	Hospital Clinico Universitario	Valencia
Spain	Instituto Valenciano Oncologia	Valencia
Taiwan	China Medical Univ Hosp	Taichung
Taiwan	National Taiwan University	Taipei
Taiwan	Taichung Veterans Gen Hosp	Taiwan
Thailand	Bumrungrad International Hosp	Bangkok
Thailand	National Cancer Institute	Bangkok
Thailand	Pramongkutklao Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hosp	Chiangmai
United Kingdom	Bristol Heamatology & Onc Ctr	Bristol
United States	Akron General Medical Center	Akron	Ohio
United States	Summa Health System	Akron	Ohio
United States	Phoebe Putney Cancer Center	Albany	Georgia
United States	Central Hem/Onc Medical Group	Alhambra	California
United States	Chicagoland Hematology Onc	Arlington Heights	Illinois
United States	Northeast Georgia Cancer Care	Athens	Georgia
United States	Lone Star Oncology Consultants	Austin	Texas
United States	Comp Blood & Cancer Center	Bakersfield	California
United States	H&J Weinberg Cancer Institute	Baltimore	Maryland
United States	SW Vermont Healthcare Onc Asoc	Bennington	Vermont
United States	Hematology Oncology Associates	Bettendorf	Iowa
United States	Billings Clinic	Billings	Montana
United States	Center for Hematology-Oncology	Boca Raton	Florida
United States	Caritas St. Elizabeth Med Ctr	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Zale P Bernstein MD - PP	Buffalo	New York
United States	Lahey Clinic Med Ctr	Burlington	Massachusetts
United States	South Bay Oncology	Campbell	California
United States	Aultman Hospital	Canton	Ohio
United States	Gabrail Cancer Center	Canton	Ohio
United States	Charleston Cancer Center	Charleston	South Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	Erlanger Health Systems	Chattanooga	Tennessee
United States	Ctr for Cancer & Hem Disease	Cherry Hill	New Jersey
United States	Weiss-Strauss Oncology Center	Chicago	Illinois
United States	Onc/Hem Care Clin Trials LLC	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Oncology Hematology Associates	Clinton	Maryland
United States	Vermont Ctr Cancer Medicine	Colchester	Vermont
United States	Ellis Fischel Cancer Center	Columbia	Missouri
United States	Maryland Oncology/Hema PA	Columbia	Maryland
United States	Mid Ohio Onc Hematology Inc	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Bay Area Cancer Research Grp	Concord	California
United States	NorthEast Medical Center	Concord	North Carolina
United States	Bassett Cancer Center	Cooperstown	New York
United States	Coastal Bend Cancer Center	Corpus Christi	Texas
United States	Texas Cancer Associates	Dallas	Texas
United States	Texas Hematology Oncology	Dallas	Texas
United States	Dayton Clinical Oncology Prog	Dayton	Ohio
United States	Halifax Medical Center	Daytona Beach	Florida
United States	Mile High Oncology	Denver	Colorado
United States	Pacific Onc & Hem Assoc	Encinitas	California
United States	Forte, Attas & Schleider	Englewood	New Jersey
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	San Juan Onco Assoc	Farmington	New Mexico
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	JPS Center for Cancer Care	Fort Worth	Texas
United States	Pacific Coast Hem/Onc	Fountain Valley	California
United States	Metrowest Cancer Center	Framingham	Massachusetts
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	Central State Medical Center	Freehold	New Jersey
United States	Cancer Care Associates	Fresno	California
United States	St. Edward Mercy Medical Ctr	Ft Smith	Arizona
United States	St. Jude Heritage Med Group	Fullerton	California
United States	Univ of Texas Medical Branch	Galveston	Texas
United States	LaGrange Oncology Associates	Geneva	Illinois
United States	The Jones Clinic	Germantown	Tennessee
United States	Ronald H. Yanagihara	Gilroy	California
United States	Adriondack Cancer Care	Glen Falls	New York
United States	Glendale Adventist Medical Ctr	Glendale	California
United States	Oncology Alliance	Glendale	Wisconsin
United States	Spectrum Health	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	BRANY	Great Neck	New York
United States	Moses Cone Reg Cncr Ctr	Greensboro	North Carolina
United States	Emerywood Hematology Oncology	High Point	North Carolina
United States	Gajera & Patel, PLLC	Hopkinsville	Kentucky
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Univ Physicians Internal Med	Huntington	West Virginia
United States	Florida Wellcare Alliance	Inverness	Florida
United States	Jackson-Madsion County Hosp	Jackson	Tennessee
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Queens Cancer Center	Jamaica	New York
United States	Freeman Cancer Institute	Joplin	Missouri
United States	Kalamazoo Hem & Onc	Kalamazoo	Michigan
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Cascade Cancer Center	Kirkland	Washington
United States	Armstrong County Memorial Hosp	Kittanning	Pennsylvania
United States	Scipps Clinic	La Jolla	California
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	La Grange Oncology Associates	Lagrange	Illinois
United States	Hem Onc Assoc Phys Lancaster	Lancaster	Pennsylvania
United States	Comp Cancer Centers of Nevada	Las Vegas	Nevada
United States	Suburban Hem-Onc Associates	Lawrenceville	Georgia
United States	NE Hematology Oncology, PC	Lincoln	Nebraska
United States	St. Barnabas Health Care Sys	Livingston	New Jersey
United States	Loma Linda Univ Medical Center	Loma Linda	California
United States	Pacific Shores Medical Group	Long Beach	California
United States	Kenmar Research Institute LLC	Los Angeles	California
United States	UCLA Medical Ctr	Los Angeles	California
United States	Consultants in Blood Disorders	Louisville	Kentucky
United States	Kentuckiana Cancer Center	Louisville	Kentucky
United States	University of Louisville	Louisville	Kentucky
United States	Dean Clinic	Madison	Wisconsin
United States	Ohio Cancer Specialists	Mansfield	Ohio
United States	Northwest Georgia Onc Centers	Marietta	Georgia
United States	Marquette General Health Sys	Marquette	Michigan
United States	Clopton Clinic	Memphis	Tennessee
United States	Jackson Memorial Hospital	Miami	Florida
United States	Crystal Run Health Care	Middletown	New York
United States	Signal Point Hem/Oncology Inc	Middletown	Ohio
United States	Medical Consultants LTD	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Inst	Minneapolis	Minnesota
United States	Montana Cancer Specialists	Missoula	Montana
United States	Sacred Heart Medical Onc Group	Mobile	Alabama
United States	Sutter Gould Med Foundation	Modesto	California
United States	Mountainside Hospital	Montclair	New Jersey
United States	West Virginia University	Morgantown	West Virginia
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Hematology Oncology Assoc SJ	Mount Holly	New Jersey
United States	Community Hospital	Munster	Indiana
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Vanderbilt University Medical	Nashville	Tennessee
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Mem Sloan Kettering Cancer Ctr	New York	New York
United States	NYU Medical Center	New York	New York
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	North Valley Hem Onc Med Grp	Northridge	California
United States	Associates in Medical Oncology	Oak Lawn	Illinois
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Hem Onc Med Grp Orange Cty	Orange	California
United States	Medical Oncology Care Assoc	Orange	California
United States	Mid-Florida Hem Oncology Ctr	Orange City	Florida
United States	Integrated Comm Onc Network	Orange Park	Florida
United States	Owensboro Medical Health Sys	Owensboro	Kentucky
United States	Ventura Co Hem-Onc Specialists	Oxnard	California
United States	The Valley Hospital	Paramus	New Jersey
United States	Onc Hem Assoc of Central IL	Peoria	Illinois
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Wilshire Oncology Medical Grp	Pomona	California
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Hematology Onc Treasure Coast	Port Saint Lucie	Florida
United States	Providence Portland Med Center	Portland	Oregon
United States	All Saints Cancer Center	Racine	Wisconsin
United States	West Suburban Cancer Center	River Forest	Illinois
United States	SW Virginia Hem Onc	Roanoke	Virginia
United States	OSF St. Anthony Med Ctr	Rockford	Illinois
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Community Cancer Center	Rutland	Vermont
United States	Mercy General Hospital	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	St. Louis Univ Care Center	Saint Louis	Missouri
United States	Los Palos Oncology & Hem	Salinas	California
United States	Kaiser Permanente	San Diego	California
United States	Naval Medical Center	San Diego	California
United States	Pacific Hematology Oncology	San Francisco	California
United States	Kaiser Permanente Santa Teresa	San Jose	California
United States	Sansum Medical Clinic, Inc.	Santa Barbara	California
United States	Santa Barbara Hem Onc Med Grp	Santa Barbara	California
United States	Central Coast Medical Oncology	Santa Maria	California
United States	The Angeles Clinic	Santa Monica	California
United States	Redwood Regional Med Grp	Santa Rosa	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	Scranton Hematology Oncology	Scranton	Pennsylvania
United States	Willis-Knighton Cancer Center	Shreveport	Louisiana
United States	Siouxland Hem-Onc Assoc LLP	Sioux City	Iowa
United States	Palmetto Hematology Oncology	Spartanburg	South Carolina
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Missouri Cancer Center, PC	St Charles	Missouri
United States	Overlook Hospital	Summit	New Jersey
United States	SUNY Upstate	Syracuse	New York
United States	Northwest Medical Specialists	Tacoma	Washington
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Providence Medical Group	Terre Haute	Indiana
United States	Toledo Community Hospital	Toledo	Ohio
United States	Cancer Care Associates	Torrance	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Assoc in Hematology Oncology	Upland	Pennsylvania
United States	Arch Medical Services	Washington	Missouri
United States	Beaufort County Hospital	Washington	North Carolina
United States	Washington Onc Hem Center PC	Washington	District of Columbia
United States	Covenant Clinic	Waterloo	Iowa
United States	Lankenau Medical Office Bldg	Wynnewood	Pennsylvania
United States	Forum Health Cancer Care Ctr	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Hong Kong,  Israel,  Italy,  Mexico,  Philippines,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	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.	Approximately 3 years	No
Secondary	Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase	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.	Approximately 3 years	No
Secondary	Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase	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.	Approximately 3 years	No
Secondary	Number of Participants With Any Adverse Events During Post-Chemotherapy Phase	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.	Approximately 3.5 years	No
Secondary	Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase	Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008).	Approximately 3 years	No
Secondary	Incidence of Study Treatment Discontinuation	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.	Approximately 3 years	No
Secondary	Overall Survival	Overall survival was defined as the length of time from randomization to death.	Approximately 3.5 years	No