Study Stopped
The study was closed to accrual due to the end of the clinical development program with cixutumumab.
Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-squamous, Non-small Cell Lung Cancer
4 other identifiers
interventional
175
1 country
165
Brief Summary
This randomized phase II trial studies how well carboplatin, paclitaxel, and bevacizumab (CPB) work when given with or without cixutumumab in treating patients with non-small cell lung cancer that is stage IV or has come back (recurrent). 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, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Other types of monoclonal antibodies, such as cixutumumab, may find tumor cells and help kill them. It is not yet known whether giving more than one drug (combination chemotherapy) together with bevacizumab is more effective when given with or without cixutumumab in treating patients with non-small cell lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2010
Longer than P75 for phase_2
165 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 7, 2009
CompletedFirst Posted
Study publicly available on registry
August 10, 2009
CompletedStudy Start
First participant enrolled
March 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedResults Posted
Study results publicly available
September 8, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2016
CompletedJune 6, 2018
May 1, 2018
5.8 years
August 7, 2009
July 26, 2016
May 3, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS)
Progression-free survival was defined as the time from randomization to progression or death without documentation of progression. For cases without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurs within 3 months following the date last known progression-free, in which case the death was counted as a failure. Progression was evaluated using RECIST 1.1 criteria and defined as: 1. At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. OR 2. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years
Secondary Outcomes (2)
Overall Survival (OS)
Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years
Proportion of Patients With Objective Response
Assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry; up to 5 years
Study Arms (2)
Arm A (CPB)
ACTIVE COMPARATORPatients receive carboplatin intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab may continue in the absence of disease progression or unacceptable toxicity.
Arm B (CPB+cixutumumab)
EXPERIMENTALPatients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed with non-squamous, non-small cell lung cancer (NSCLC)
- Advanced NSCLC defined as either recurrent disease after prior radiation or surgery or stage IV (M1a or M1b) based on the TNM staging system (American Joint Committee on Cancer \[AJCC\] 2009)
- Measurable disease as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). All sites of disease (of target and non-target disease sites) must be obtained within 4 weeks prior to randomization
- A head computed tomography (CT) or magnetic resonance imaging (MRI) required within 4 weeks prior to randomization
- Prior radiation therapy (RT) is allowed if it has been completed 3 weeks prior to randomization and patient has recovered from any adverse events related to RT
- Brain metastases are allowed, provided they have been treated with surgery and/or radiotherapy, the patient is neurologically stable, and repeat brain imaging shows no progression in the brain; at least 6 weeks should have elapsed from the time of craniotomy and at least 4 weeks from radiotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Absolute neutrophil count (ANC) ≥ 1500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin within institutional upper limit of normal (ULN)
- Serum creatinine ≤ 1.5 x ULN
- Fasting blood glucose within normal range (fasting \< 120 mg/dL or below ULN)
- Alkaline phosphatase (ALP) ≤ 3 x ULN
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
- Urine dipstick must be ≤ 0-1+ within 2 weeks (14 days) of randomization; if urine dipstick result is \> 1+, a calculation of urine protein creatinine (UPC) ratio is required; patients must have a UPC ratio \< 1.0 to participate in the study
- +3 more criteria
You may not qualify if:
- Prior chemotherapy or biologic/molecular targeted therapy for advanced NSCLC. Prior chemotherapy and/or biological/molecular targeted therapy as part of initial potentially curative therapy (one regimen of induction and/or adjuvant and/or concurrent chemoradiotherapy) was allowed provided it had been completed 1 year or more prior to randomization
- Prior treatment with IMC-A12 or another insulin-like growth factor 1 receptor (IGF-1R) inhibitor
- Patients on therapeutic anticoagulation; patient's international normalized ratio (INR) must be ≤ 1.5 or partial thromboplastin time (PTT) ≤ upper limits of normal within 2 weeks prior to randomization to be eligible; prophylactic anticoagulation of venous access devices is allowed provided the above criteria have been met
- Prior allergic reaction to compounds of chemical or biologic composition similar to those of IMC-A12
- Hypersensitivity to any component of bevacizumab
- Poorly controlled diabetes mellitus
- History of other invasive malignancies unless there is no active disease and all treatment has been completed ≥ 3 years prior to randomization; patients with history of in-situ malignancies and curatively resected nonmelanomatous skin cancer are eligible
- History of thrombotic or hemorrhagic disorders
- History of bleeding diathesis or coagulopathy
- ≥ grade 2 bleeding or any bleeding requiring intervention within 4 weeks prior to randomization
- History of gross hemoptysis (defined as ≥ 1/2 teaspoon of bright red blood)
- Any of the following within 6 months prior to randomization:
- Abdominal fistula
- Gastrointestinal perforation
- Intra-abdominal abscess
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (165)
The Medical Center of Aurora
Aurora, Colorado, 80012, United States
Boulder Community Hospital
Boulder, Colorado, 80301, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907, United States
Porter Adventist Hospital
Denver, Colorado, 80210, United States
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218, United States
SCL Health Saint Joseph Hospital
Denver, Colorado, 80218, United States
Rose Medical Center
Denver, Colorado, 80220, United States
Colorado Cancer Research Program NCORP
Denver, Colorado, 80222, United States
Swedish Medical Center
Englewood, Colorado, 80113, United States
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81502, United States
North Colorado Medical Center
Greeley, Colorado, 80631, United States
Saint Anthony Hospital
Lakewood, Colorado, 80228, United States
Littleton Adventist Hospital
Littleton, Colorado, 80122, United States
Sky Ridge Medical Center
Lone Tree, Colorado, 80124, United States
Longmont United Hospital
Longmont, Colorado, 80501, United States
McKee Medical Center
Loveland, Colorado, 80539, United States
Saint Mary Corwin Medical Center
Pueblo, Colorado, 81004, United States
North Suburban Medical Center
Thornton, Colorado, 80229, United States
SCL Health Lutheran Medical Center
Wheat Ridge, Colorado, 80033, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
The Hospital of Central Connecticut
New Britain, Connecticut, 06050, United States
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, 06360, United States
Charlotte Hungerford Hospital Center for Cancer Care
Torrington, Connecticut, 06790, United States
Lakeland Regional Cancer Center
Lakeland, Florida, 33805, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, 31405, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Saint Joseph Hospital
Chicago, Illinois, 60657, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Hinsdale Hematology Oncology Associates Incorporated
Hinsdale, Illinois, 60521, United States
Swedish American Hospital
Rockford, Illinois, 61104, United States
SwedishAmerican Regional Cancer Center/ACT
Rockford, Illinois, 61114, United States
McFarland Clinic PC-William R Bliss Cancer Center
Ames, Iowa, 50010, United States
Mercy Hospital
Cedar Rapids, Iowa, 52403, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403, United States
Medical Oncology and Hematology Associates-West Des Moines
Clive, Iowa, 50325, United States
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
Iowa-Wide Oncology Research Coalition NCORP
Des Moines, Iowa, 50309, United States
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, 50309, United States
Medical Oncology and Hematology Associates-Laurel
Des Moines, Iowa, 50314, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
Iowa Lutheran Hospital
Des Moines, Iowa, 50316, United States
Ottumwa Regional Health Center
Ottumwa, Iowa, 52501, United States
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101, United States
Mercy Medical Center-Sioux City
Sioux City, Iowa, 51104, United States
Saint Luke's Regional Medical Center
Sioux City, Iowa, 51104, United States
Cancer Center of Kansas - Chanute
Chanute, Kansas, 66720, United States
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, 67801, United States
Cancer Center of Kansas - El Dorado
El Dorado, Kansas, 67042, United States
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, 66701, United States
Cancer Center of Kansas-Independence
Independence, Kansas, 67301, United States
Cancer Center of Kansas-Kingman
Kingman, Kansas, 67068, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
Cancer Center of Kansas-Liberal
Liberal, Kansas, 67901, United States
Cancer Center of Kansas - McPherson
McPherson, Kansas, 67460, United States
Cancer Center of Kansas - Newton
Newton, Kansas, 67114, United States
Cancer Center of Kansas - Parsons
Parsons, Kansas, 67357, United States
Cancer Center of Kansas - Pratt
Pratt, Kansas, 67124, United States
Cancer Center of Kansas - Salina
Salina, Kansas, 67401, United States
Cancer Center of Kansas - Wellington
Wellington, Kansas, 67152, United States
Associates In Womens Health
Wichita, Kansas, 67208, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita, Kansas, 67208, United States
Cancer Center of Kansas - Main Office
Wichita, Kansas, 67214, United States
Via Christi Regional Medical Center
Wichita, Kansas, 67214, United States
Wichita NCI Community Oncology Research Program
Wichita, Kansas, 67214, United States
Cancer Center of Kansas - Winfield
Winfield, Kansas, 67156, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995, United States
Michigan Cancer Research Consortium CCOP
Ann Arbor, Michigan, 48106, United States
Oakwood Hospital and Medical Center
Dearborn, Michigan, 48124, United States
Saint John Hospital and Medical Center
Detroit, Michigan, 48236, United States
Hurley Medical Center
Flint, Michigan, 48502, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, 48532, United States
Allegiance Health
Jackson, Michigan, 49201, United States
Borgess Medical Center
Kalamazoo, Michigan, 49001, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007, United States
Sparrow Hospital
Lansing, Michigan, 48912, United States
Saint Mary Mercy Hospital
Livonia, Michigan, 48154, United States
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341, United States
Saint Joseph Mercy Port Huron
Port Huron, Michigan, 48060, United States
Saint Mary's of Michigan
Saginaw, Michigan, 48601, United States
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093, United States
Sanford Clinic North-Bemidgi
Bemidji, Minnesota, 56601, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805, United States
Miller-Dwan Hospital
Duluth, Minnesota, 55805, United States
Fairview-Southdale Hospital
Edina, Minnesota, 55435, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
New Ulm Medical Center
New Ulm, Minnesota, 56073, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379, United States
Lakeview Hospital
Stillwater, Minnesota, 55082, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Minnesota Oncology and Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Alegent Health Lakeside Hospital
Omaha, Nebraska, 68130, United States
Veterans Adminstration New Jersey Health Care System
East Orange, New Jersey, 07018-1095, United States
Hunterdon Medical Center
Flemington, New Jersey, 08822, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07101, United States
Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Sanford Clinic North-Fargo
Fargo, North Dakota, 58122, United States
Sanford Medical Center-Fargo
Fargo, North Dakota, 58122, United States
Summa Akron City Hospital/Cooper Cancer Center
Akron, Ohio, 44304, United States
Mary Rutan Hospital
Bellefontaine, Ohio, 43311, United States
Mercy Medical Center
Canton, Ohio, 44708, United States
Adena Regional Medical Center
Chillicothe, Ohio, 45601, United States
The Christ Hospital
Cincinnati, Ohio, 45219, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Columbus NCI Community Oncology Research Program
Columbus, Ohio, 43215, United States
Grant Medical Center
Columbus, Ohio, 43215, United States
Mount Carmel Health Center West
Columbus, Ohio, 43222, United States
Doctors Hospital
Columbus, Ohio, 43228, United States
Grady Memorial Hospital
Delaware, Ohio, 43015, United States
Fairfield Medical Center
Lancaster, Ohio, 43130, United States
Saint Rita's Medical Center
Lima, Ohio, 45801, United States
Marietta Memorial Hospital
Marietta, Ohio, 45750, United States
Knox Community Hospital
Mount Vernon, Ohio, 43050, United States
Licking Memorial Hospital
Newark, Ohio, 43055, United States
Southern Ohio Medical Center
Portsmouth, Ohio, 45662, United States
Springfield Regional Medical Center
Springfield, Ohio, 45505, United States
Genesis Healthcare System Cancer Care Center
Zanesville, Ohio, 43701, United States
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
PinnacleHealth Cancer Center-Community Campus
Harrisburg, Pennsylvania, 17109, United States
Geisinger Medical Center-Cancer Center Hazleton
Hazleton, Pennsylvania, 18201, United States
Saint Mary Medical and Regional Cancer Center
Langhorne, Pennsylvania, 19047, United States
Paoli Memorial Hospital
Paoli, Pennsylvania, 19301, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Pottstown Memorial Medical Center
Pottstown, Pennsylvania, 19464, United States
Geisinger Medical Group
State College, Pennsylvania, 16801, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096, United States
Main Line Health NCORP
Wynnewood, Pennsylvania, 19096, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Avera McKennan Hospital and University Health Center
Sioux Falls, South Dakota, 57105, United States
Dallas VA Medical Center
Dallas, Texas, 75216, United States
Parkland Memorial Hospital
Dallas, Texas, 75235, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
West Virginia University Charleston
Charleston, West Virginia, 25304, United States
Fox Valley Hematology and Oncology
Appleton, Wisconsin, 54913, United States
Marshfield Clinic Cancer Center at Sacred Heart
Eau Claire, Wisconsin, 54701, United States
Dean Hematology and Oncology Clinic
Madison, Wisconsin, 53717, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017, United States
Oconomowoc Memorial Hospital-ProHealth Care Inc
Oconomowoc, Wisconsin, 53066, United States
Waukesha Memorial Hospital
Waukesha, Wisconsin, 53188, United States
Related Publications (2)
Argiris, A., Lee, J., Leach, J.W., Schiller, J.H.: Safety analysis of a phase II randomized trial of carboplatin (C), Paclitaxel (P), bevacizumab (B) with or without cixutumumab (CX) in patients (pts) with advanced non-squamous, non-small cell lung cancer (NSCLC). J Clin Oncol 2014;31(15s). Abstract e19018.
RESULTArgiris A, Lee JW, Stevenson J, Sulecki MG, Hugec V, Choong NW, Saltzman JN, Song W, Hansen RM, Evans TL, Ramalingam SS, Schiller JH. Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small-cell lung cancer: a trial of the ECOG-ACRIN Cancer Research Group (E3508). Ann Oncol. 2017 Dec 1;28(12):3037-3043. doi: 10.1093/annonc/mdx534.
PMID: 28950351DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Statistician
- Organization
- ECOG-ACRIN Statistical Office
Study Officials
- PRINCIPAL INVESTIGATOR
Athanassios (Ethan) Argiris
ECOG-ACRIN Cancer Research Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 7, 2009
First Posted
August 10, 2009
Study Start
March 1, 2010
Primary Completion
January 1, 2016
Study Completion
November 1, 2016
Last Updated
June 6, 2018
Results First Posted
September 8, 2016
Record last verified: 2018-05
Data Sharing
- IPD Sharing
- Will share
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.