Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01107626
• Other study ID #: E5508
• Status: Completed
• Phase: Phase 3
• Start date: October 25, 2010
• Est. completion date: August 17, 2021

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer.

Description:

OBJECTIVES:

Primary

• To compare the overall survival (OS) of patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with maintenance therapy with bevacizumab vs pemetrexed disodium vs bevacizumab and pemetrexed disodium following induction therapy.

Secondary

• To determine the response rate in patients treated with these regimens.

• To evaluate the progression-free survival (PFS) of patients treated with these regimens.

• To define the toxicity of these regimens in these patients.

• To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA, and ERCC-118 TT in patients treated with induction therapy comprising paclitaxel, carboplatin and bevacizumab and determine the association between genotypes and response rate.

• To determine the association between bevacizumab and pemetrexed disodium population pharmacokinetics and patient-specific covariate with bevacizumab or pemetrexed disodium toxicity.

• To determine the frequency of TSER*3 polymorphisms in NSCLC and the association between TSER polymorphisms and benefit from pemetrexed disodium.

• To evaluate TS and ERCC1 expression by RT-PCR and MTAP mutations in existing tumor specimens as a predictor of pemetrexed disodium response.

• To evaluate polymorphisms within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 collectively or monogenically as markers for variation in efficacious and/or toxic response of individuals to treatment with taxanes.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender (male vs female), stage of disease (IIIB-T4Nx [with nodule in ipsilateral lung lobe and not candidate for combined chemotherapy and radiation] and IV M1a vs IV M1b vs recurrent), best response to first-time therapy (complete response/partial response vs stable disease), and smoking status (never vs smoker).

• Induction therapy (Arm I): Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

• Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Treatment begins within 6 weeks of the last day of induction chemotherapy administration.

• Arm A: Patients receive bevacizumab IV over 30-90 minutes on day 1.

• Arm B: Patients receive pemetrexed disodium IV over 10 minutes on day 1.

• Arm C: Patients receive bevacizumab as in arm A and pemetrexed as in arm B. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for correlative studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 2-5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1516
• Est. completion date: August 17, 2021
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (Step 1 Induction Therapy):

• Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)

• Predominant non-squamous histology (NSCLC not otherwise specified allowed). Mixed tumors are categorized by the predominant cell type.

• Stage IV disease including M1a or M1b stages or recurrent disease

• Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy

• At least 12 months since prior adjuvant chemotherapy

• At least 2 weeks since prior radiotherapy

• Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy

• Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration

• ECOG (Eastern Cooperative Oncology Group) performance status 0-1

• Leukocytes = 3,000/mm^3

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Total bilirubin = institutional upper limit of normal (ULN)

• AST and ALT = 3 times ULN

• Creatinine = institutional ULN OR creatinine clearance = 60 mL/min

• Urine protein:urine dipstick = 0-1+ (if > 1+, urine protein creatinine ratio must be < 1)

• Measurable or non-measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumours) criteria

• Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet

• Concurrent therapeutic anti-coagulation allowed

• Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy

Exclusion Criteria (Step 1 Induction Therapy):

• Prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ

• Prior systemic chemotherapy for advanced stage lung cancer

• Prior use of paclitaxel, pemetrexed disodium, or bevacizumab

• Major hemoptysis within the past 4 weeks

• Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements

• History of arterial thrombotic events or major bleeding within the past 12 months

• Major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration. Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol.

• Core biopsy within 7 days of registration

• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months

• Clinically significant cardiovascular disease

• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• History of serious non-healing wounds, ulcers, or bone fractures

• Cavitary lesions in the lungs

• Pregnant or nursing

• Concurrent anti-retroviral therapy in patients with HIV infection

Inclusion Criteria (Step 2 Maintenance Therapy):

• Patient must have an overall stable or better response after 4 courses of induction therapy

• ECOG (Eastern Cooperative Oncology Group) performance status 0-1

• Patients must be registered to Step 2 within 6 weeks of the last day of chemotherapy administration on Step 1

• Acceptable bone marrow, renal and hepatic function within 2 weeks of registration

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Paclitaxel
Given IV
• Carboplatin
Given IV

Biological:
• Bevacizumab
Given IV

Drug:
• Pemetrexed Disodium Heptahydrate
Given IV

Locations

Country	Name	City	State
United States	Oncology Services of Aberdeen	Aberdeen	South Dakota
United States	Hendrick Cancer Center	Abilene	Texas
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	Georgia
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Regional Medical Center	Anniston	Alabama
United States	Langlade Memorial Hospital	Antigo	Wisconsin
United States	Randolph Hospital	Asheboro	North Carolina
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sturdy Memorial Hospital	Attleboro	Massachusetts
United States	Auburn Regional Center for Cancer Care	Auburn	Washington
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Kaiser Permanente at Woodlawn Medical Center	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana
United States	Cleveland Clinic Beachwood Family Health and Surgery Center	Beachwood	Ohio
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Overlake Cancer Center at Overlake Hospital Medical Center	Bellevue	Washington
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Central Care Cancer Center at Carrie J. Babb Cancer Center	Bolivar	Missouri
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. Joseph's Medical Center	Brainerd	Minnesota
United States	Skaggs Cancer Center at Skaggs Regional Medical Center	Branson	Missouri
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Iowa Blood and Cancer Care	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	St. Luke's Hospital	Cedar Rapids	Iowa
United States	Providence Centralia Hospital	Centralia	Washington
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	Resurrection Medical Center	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Saint Joseph Hospital	Chicago	Illinois
United States	Swedish Covenant Hospital	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Mercy Cancer Center - West Lakes	Clive	Iowa
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Heartland Oncology and Hematology	Council Bluffs	Iowa
United States	Ochsner Health Center - Covington	Covington	Louisiana
United States	Regional Cancer Center at Western Maryland Health System - Sacred Heart Campus	Cumberland	Maryland
United States	Praxair Cancer Center at Danbury Hospital	Danbury	Connecticut
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Mercy Fitzgerald Hospital	Darby	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	North Broward Medical Center	Deerfield Beach	Florida
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Kaiser Permanente - Denver	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Cancer Centers of the Carolinas - Easley	Easley	South Carolina
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Ephrata Cancer Center at Ephrata Community Hospital	Ephrata	Pennsylvania
United States	Regional Cancer Center - Erie	Erie	Pennsylvania
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	St. Francis Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	North Bay Cancer Center	Fairfield	California
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Dakota Cancer Institute at Dakota Clinic - South University	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Roger Maris Cancer Center at MeritCare Hospital	Fargo	North Dakota
United States	St. Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Frederick Memorial Hospital Regional Cancer Therapy Center	Frederick	Maryland
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Leonard C. Ferguson Cancer Center	Freeport	Illinois
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania
United States	Kaiser Permanente - Gaithersburg Medical Center	Gaithersburg	Maryland
United States	Delnor Hospital - Geneva	Geneva	Illinois
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Hospital Cancer Center	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Virginia Oncology Associates - Hampton	Hampton	Virginia
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	PinnacleHealth Regional Cancer Center at Polyclinic Hospital	Harrisburg	Pennsylvania
United States	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	St. Peter's Hospital	Helena	Montana
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cleveland Clinic Cancer Center	Independence	Ohio
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	West Tennessee Cancer Center at Jackson-Madison County General Hospital	Jackson	Tennessee
United States	Mercy Regional Cancer Center	Janesville	Wisconsin
United States	Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	St. John's Regional Medical Center	Joplin	Missouri
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Providence Medical Center	Kansas City	Kansas
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	La Grange Memorial Hospital	La Grange	Illinois
United States	Clarian Arnett Cancer Care	Lafayette	Indiana
United States	Kaiser Permanente - Lafayette	Lafayette	Colorado
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility	Largo	Maryland
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	St. Joseph Regional Medical Center	Lewiston	Idaho
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Parvin Radiation Oncology	Liberty	Missouri
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	St. Rita's Medical Center	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Todd Cancer Institute at Long Beach Memorial Medical Center	Long Beach	California
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Vince Lombardi Cancer Clinic - Marinette	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Upper Michigan Cancer Center at Marquette General Hospital	Marquette	Michigan
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Kaiser Permanente Tysons Corner Medical Center	McLean	Virginia
United States	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania
United States	Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	Suniti Medical Corporation	Merrillville	Indiana
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Southwest General Health Center	Middleburg Heights	Ohio
United States	Wheaton Franciscan Cancer Care - St. Joseph	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Trinity CancerCare Center	Minot	North Dakota
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Community Hospital of the Monterey Peninsula Comprehensive Cancer Center	Monterey	California
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey
United States	D.N. Greenwald Center	Mukwonago	Wisconsin
United States	Saint Luke's Mountain States Tumor Institute	Nampa	Idaho
United States	Oncology Center at St. Joseph Hospital	Nashua	New Hampshire
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana
United States	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	UMDNJ University Hospital	Newark	New Jersey
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	Cancer Care Associates - Norman	Norman	Oklahoma
United States	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma
United States	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Lakeside Hospital	Omaha	Nebraska
United States	UHHS Chagrin Highlands Medical Center	Orange Village	Ohio
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's Hospital - South	Overland Park	Kansas
United States	Mitchell Memorial Cancer Center at Owensboro Medical Health System	Owensboro	Kentucky
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Feather River Hospital Cancer Center	Paradise	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	Parma Community General Hospital	Parma	Ohio
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Sacred Heart Medical Oncology	Pensacola	Florida
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	Iris V. Henderson Cancer Center at Mercy Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Jordan Hospital Club Cancer Center	Plymouth	Massachusetts
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	CCOP - Kansas City	Prairie Village	Kansas
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	St. Joseph Medical Center	Reading	Pennsylvania
United States	Annie Penn Cancer Center	Reidsville	North Carolina
United States	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Center for Cancer Care at OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Mercy Clinic Cancer and Hematology - Rolla	Rolla	Missouri
United States	Phelps County Regional Medical Center	Rolla	Missouri
United States	Sutter Cancer Center at Roseville Medical Center	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Community Cancer Center at Rutland Regional Medical Center	Rutland	Vermont
United States	Sutter Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	St. Anthony's Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Salinas Valley Memorial Hospital	Salinas	California
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania
United States	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Pacific Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Grand View Hospital	Sellersville	Pennsylvania
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Rockwood Clinic Cancer Treatment Center	Spokane	Washington
United States	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Stanford Cancer Center	Stanford	California
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	Cleveland Clinic Foundation - Strongsville	Strongsville	Ohio
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center	Summit	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Allenmore Hospital	Tacoma	Washington
United States	CCOP - Northwest	Tacoma	Washington
United States	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	St. Clare Hospital	Tacoma	Washington
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Mountain States Tumor Institute at St. Luke's	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Faxton Regional Cancer Center	Utica	New York
United States	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia
United States	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Central Dupage Cancer Center	Warrenville	Illinois
United States	Kaiser Permanente at Capitol Hill Medical Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Covenant Cancer Treatment Center	Waterloo	Iowa
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Oncology Alliance, SC - Milwaukee - West	Wauwatosa	Wisconsin
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Methodist West Hospital	West Des Moines	Iowa
United States	UHHS Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic Florida - Weston	Weston	Florida
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Dickstein Cancer Treatment Center at White Plains Hospital Center	White Plains	New York
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Susquehanna Cancer Center at Divine Providence Hospital	Williamsport	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts
United States	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Air Force Base	Ohio
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ramalingam SS, Dahlberg SE, Belani CP, Saltzman JN, Pennell NA, Nambudiri GS, McCann JC, Winegarden JD, Kassem MA, Mohamed MK, Rothman JM, Lyss AP, Horn L, Stinchcombe TE, Schiller JH. Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Association Between Genotypes and Response Rate	To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA and ERCC-118 TT in patients with NSCLC receiving paclitaxel, carboplatin and bevacizumab therapy and determine the association between genotypes and response rate.	Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5
Other	The Association Between Bevacizumab and Pemetrexed Population Pharmacokinetics and Patient Specific Covariates With Bevacizumab or Pemetrexed Toxicity		Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
Other	The Frequency of TSER*3 Polymorphisms in NSCLC and the Association Between TSER Polymorphisms and Benefit From Pemetrexed		Assessed every 3 months for 2 years and every 6 months for years 3-5
Other	The Association Between TS and ERCC1 Expression and Pemetrexed Response		Assessed every 3 months for 2 years and every 6 months for years 3-5
Other	The Associations Between Polymorphisms Within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 Collectively or Monogenically and Efficacy and/or Toxicities		Assessed every 3 months for 2 years and every 6 months for years 3-5
Primary	Overall Survival	Overall survival is defined as the time from randomization to death or date last known alive.; The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.	Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5
Secondary	Progression-free Survival	Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is evaluated based on RECIST criteria and defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on current step. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.; The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.	Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5
Secondary	Response Rate	Response is evaluated based on RECIST criteria v1.1 and defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the current step's baseline sum diameters.; The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.	Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.