Three-Arm Randomized Phase II Study of Carboplatin and Paclitaxel in Combination With Cetuximab, IMC-A12 or Both in Patients With Advanced Non-Small Cell Lung Cancer Who Will Not Receive Bevacizumab-Based Therapy
PRIMARY OBJECTIVES:
I. To evaluate the progression-free survival of patients with NSCLC randomized to
carboplatin plus paclitaxel plus cetuximab or carboplatin plus paclitaxel plus IMC-A12
(cixutumumab) or carboplatin plus paclitaxel plus cetuximab plus IMC-A12.
SECONDARY OBJECTIVES:
I. To evaluate the response rate, disease control rate (complete response plus partial
response plus stable disease), and toxicities for each arm.
II. To evaluate EGFR by IHC, mutation, and gene copy number, IGF-1R and IGF-2R expression
(both phosphorylated and unphosphorylated states), expression of p-AKT by IHC, and k-ras
mutation.
III. Plasma-based biomarkers will be evaluated for total and free insulin-like growth factor
1 and 2, IGF-growth factor binding protein 3 (IGFBP3) and circulating levels of EGF and TGF
alpha.
IV. To evaluate overall survival on each of the three arms.
OUTLINE: This is a multicenter study. Patients are stratified according to gender and
histology (squamous cell vs non-squamous cell). Patients are randomized to 1 of 3 treatment
arms.
ARM I: Patients receive carboplatin intravenously (IV) over 15-30 minutes and paclitaxel IV
over 3 hours on days 1 and 22 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and
36. Treatment repeats every 42 days for 2 courses. Patients with stable or responding
disease after 2 courses proceed to maintenance therapy with cetuximab alone on days 1, 8,
15, 22, 29, and 36. Treatment with cetuximab repeats every 42 days in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive carboplatin and paclitaxel as in arm I. Patients also receive
cixutumumab IV over 1 hour on days 1, 15, and 29. Treatment repeats every 42 days for 2
courses. Patients with stable or responding disease after 2 courses proceed to maintenance
therapy with cixutumumab alone on days 1, 15, and 29. Treatment with cixutumumab repeats
every 42 days in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive carboplatin, paclitaxel, and cetuximab as in arm I. Patients also
receive cixutumumab as in arm II. Treatment repeats every 42 days for 2 courses. Patients
with stable or responding disease after 2 courses proceed to maintenance therapy with
cetuximab as in arm I and cixutumumab as in arm II.
Tumor tissue samples are collected at baseline for analysis of EGFR expression by IHC,
mutation, and gene copy number; IGF-1R and IGF-2R expression (both phosphorylated and
unphosphorylated states); p-AKT expression by IHC; and k-ras mutation. Blood, serum, and
plasma samples are collected periodically for biomarker analysis.
After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 1 year.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS)
From randomization to death or disease progression, whichever occurs first, assessed up to 3 years
No
Nasser Hanna
Principal Investigator
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
NCI-2011-01976
NCT00986674
September 2009
Name | Location |
---|---|
Hurley Medical Center | Flint, Michigan 48503 |
Boulder Community Hospital | Boulder, Colorado 80301-9019 |
Porter Adventist Hospital | Denver, Colorado 80210 |
Rose Medical Center | Denver, Colorado 80220 |
Swedish Medical Center | Englewood, Colorado 80110 |
Sky Ridge Medical Center | Lone Tree, Colorado 80124 |
North Suburban Medical Center | Thornton, Colorado 80229 |
Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
Borgess Medical Center | Kalamazooaa, Michigan 49001 |
Fairview Ridges Hospital | Burnsville, Minnesota 55337 |
United Hospital | St. Paul, Minnesota 55102 |
Ridgeview Medical Center | Waconia, Minnesota 55387 |
Geisinger Medical Center | Danville, Pennsylvania 17822-0001 |
Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
Marshfield Clinic | Marshfield, Wisconsin 54449 |
Methodist Medical Center of Illinois | Peoria, Illinois 61636 |
Memorial Hospital of South Bend | South Bend, Indiana 46601 |
Newark Beth Israel Medical Center | Newark, New Jersey 07112 |
Via Christi Regional Medical Center | Wichita, Kansas 67214 |
Scott and White Memorial Hospital | Temple, Texas 76508 |
Medical Center of Central Georgia | Macon, Georgia 31201 |
University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
North Colorado Medical Center | Greeley, Colorado 80631 |
McKee Medical Center | Loveland, Colorado 80539 |
Cancer Center of Kansas - Chanute | Chanute, Kansas 66720 |
Cancer Center of Kansas - Dodge City | Dodge City, Kansas 67801 |
Cancer Center of Kansas - Newton | Newton, Kansas 67114 |
Cancer Center of Kansas - Salina | Salina, Kansas 67042 |
Cancer Center of Kansas - Wellington | Wellington, Kansas 67152 |
Associates in Womens Health | Wichita, Kansas 67203 |
Cancer Center of Kansas - Winfield | Winfield, Kansas 67156 |
Adena Regional Medical Center | Chillicothe, Ohio 54601 |
Grady Memorial Hospital | Delaware, Ohio 43015 |
Fairfield Medical Center | Lancaster, Ohio 43130 |
Paoli Memorial Hospital | Paoli, Pennsylvania 19301-1792 |
Elkhart General Hospital | Elkhart, Indiana 46515 |
University Medical Center of Southern Nevada | Las Vegas, Nevada 89102 |
Memorial Hospital | Carthage, Illinois 62321 |
Galesburg Clinic | Galesburg, Illinois 61401 |
Mason District Hospital | Havana, Illinois 62644 |
McDonough District Hospital | Macomb, Illinois 61455 |
BroMenn Regional Medical Center | Normal, Illinois 61761 |
Proctor Hospital | Peoria, Illinois 61614 |
Perry Memorial Hospital | Princeton, Illinois 61356 |
Community Cancer Center of Monroe | Monroe, Michigan 48162 |
Creighton University Medical Center | Omaha, Nebraska 68131-2197 |
Lima Memorial Hospital | Lima, Ohio 45804 |
Mercy Hospital of Tiffin | Tiffin, Ohio 44883 |
Fulton County Health Center | Wauseon, Ohio 43567 |
Bryn Mawr Hospital | Bryn Mawr, Pennsylvania 19010 |
Exempla Lutheran Medical Center | Wheat Ridge, Colorado 80033 |
Eureka Hospital | Eureka, Illinois 61530 |
Mercy Hospital | Coon Rapids, Minnesota 55433 |
Graham Hospital Association | Canton, Illinois 61520 |
Holy Family Medical Center | Des Plaines, Illinois 60016 |
Saint Joseph Medical Center | Joliet, Illinois 60435 |
Trinity Medical Center | Moline, Illinois 61265-1291 |
Pekin Hospital | Pekin, Illinois 61554 |
Bixby Medical Center | Adrian, Michigan 49221 |
Saint Joseph Mercy Hospital | Ann Arbor, Michigan 48106 |
Fairview-Southdale Hospital | Edina, Minnesota 55435 |
Abbott-Northwestern Hospital | Minneapolis, Minnesota 55407 |
Saint Francis Regional Medical Center | Shakopee, Minnesota 55379 |
Rice Memorial Hospital | Willmar, Minnesota 56201 |
Saint Luke's Hospital | Maumee, Ohio 43537 |
Lancaster General Hospital | Lancaster, Pennsylvania 17604-3555 |
Geisinger Medical Group | State College, Pennsylvania 16801 |
Fox Valley Hematology and Oncology | Appleton, Wisconsin 54911 |
Cancer Center of Kansas - Fort Scott | Fort Scott, Kansas 66701 |
Cancer Center of Kansas-Independence | Independence, Kansas 67301 |
Lawrence Memorial Hospital | Lawrence, Kansas 66044 |
Mary Rutan Hospital | Bellefontaine, Ohio 43311 |
Knox Community Hospital | Mount Vernon, Ohio 43050 |
Fisher-Titus Medical Center | Norwalk, Ohio 44857 |
Marshfield Clinic Cancer Care at Regional Cancer Center | Eau Claire, Wisconsin 54701 |
UW Cancer Center Johnson Creek | Johnson Creek, Wisconsin 53038 |
Marshfield Clinic - Weston Center | Weston, Wisconsin 54476 |
Marshfield Clinic - Wisconsin Rapids Center | Wisconsin Rapids, Wisconsin 54494 |
Longmont United Hospital | Longmont, Colorado 80501 |
Greater Baltimore Medical Center | Baltimore, Maryland 21204 |
Manchester Memorial Hospital | Manchester, Connecticut 06040-4188 |
University of Virginia | Charlottesville, Virginia 22908 |
University of Pittsburgh | Pittsburgh, Pennsylvania 15261 |
Case Western Reserve University | Cleveland, Ohio 44106 |
Albert Einstein Medical Center | Philadelphia, Pennsylvania 19141 |
Riverside Methodist Hospital | Columbus, Ohio 43214 |
Licking Memorial Hospital | Newark, Ohio 43055-2899 |
Columbus CCOP | Columbus, Ohio 43206 |
Indiana University Medical Center | Indianapolis, Indiana 46202 |
Presbyterian - Saint Lukes Medical Center - Health One | Denver, Colorado 80218 |
Wichita CCOP | Wichita, Kansas 67214-3882 |
Alegent Health Immanuel Medical Center | Omaha, Nebraska 68122 |
Alegent Health Bergan Mercy Medical Center | Omaha, Nebraska 68124 |
Flower Hospital | Sylvania, Ohio 43560-2197 |
Metro-Minnesota CCOP | St. Louis Park, Minnesota |
Lankenau Hospital | Wynnewood, Pennsylvania 19096 |
Northern Indiana Cancer Research Consortium | South Bend, Indiana |
OSF Saint Francis Medical Center | Peoria, Illinois 61637 |
The Medical Center of Aurora | Aurora, Colorado 80012 |
Penrose-Saint Francis Healthcare | Colorado Springs, Colorado 80907 |
Saint Anthony Central Hospital | Denver, Colorado 80204 |
Exempla Saint Joseph Hospital | Denver, Colorado 80218 |
Colorado Cancer Research Program CCOP | Denver, Colorado 80224-2522 |
Saint Mary's Hospital and Regional Medical Center | Grand Junction, Colorado 81502 |
Saint Mary Corwin Medical Center | Pueblo, Colorado 81004 |
Danbury Hospital | Danbury, Connecticut 06810 |
Saint Francis Hospital and Medical Center | Hartford, Connecticut 06105 |
Evanston CCOP-NorthShore University HealthSystem | Evanston, Illinois 60201 |
Stoffel, Thomas J MD (UIA Investigator) | Moline, Illinois 61265 |
Garneau, Stewart C MD (UIA Investigator) | Moline, Illinois 61265 |
Sharis, Christine M MD (UIA Investigator) | Moline, Illinois 61265 |
Porubcin, Michael MD (UIA Investigator) | Moline, Illinois 61265 |
Community Cancer Center Foundation | Normal, Illinois 61761 |
Illinois CancerCare-Ottawa Clinic | Ottawa, Illinois 61350 |
Ottawa Regional Hospital and Healthcare Center | Ottawa, Illinois 61350 |
Pekin Cancer Treatment Center | Pekin, Illinois 61554 |
Illinois Oncology Research Association CCOP | Peoria, Illinois 61615 |
Illinois CancerCare-Peoria | Peoria, Illinois 61615 |
Illinois Valley Hospital | Peru, Illinois 61354 |
Saint Margaret's Hospital | Spring Valley, Illinois 61362 |
Richard L. Roudebush Veterans Affairs Medical Center | Indianapolis, Indiana 46202 |
Wishard Hospital | Indianapolis, Indiana 46202 |
Constantinou, Costas L MD (UIA Investigator) | Bettendorf, Iowa 52722 |
Cedar Rapids Oncology Association | Cedar Rapids, Iowa 52403 |
Mercy Hospital | Cedar Rapids, Iowa 52403 |
Mercy Medical Center-Sioux City | Sioux City, Iowa 51104 |
Saint Luke's Regional Medical Center | Sioux City, Iowa 51104 |
Cancer Center of Kansas - El Dorado | El Dorado, Kansas 67042 |
Cancer Center of Kansas-Kingman | Kingman, Kansas 67068 |
Cancer Center of Kansas - Parsons | Parsons, Kansas 67357 |
Cancer Center of Kansas - Pratt | Pratt, Kansas 67124 |
Cancer Center of Kansas-Wichita Medical Arts Tower | Wichita, Kansas 67208 |
Cancer Center of Kansas - Main Office | Wichita, Kansas 67214 |
Hickman Cancer Center | Adrian, Michigan 49221 |
Michigan Cancer Research Consortium Community Clinical Oncology Program | Ann Arbor, Michigan 48106 |
Oakwood Hospital | Dearborn, Michigan 48123 |
Saint John Hospital and Medical Center | Detroit, Michigan 48236 |
Green Bay Oncology - Escanaba | Escanaba, Michigan 49431 |
Green Bay Oncology - Iron Mountain | Iron Mountain, Michigan 49801 |
Allegiance Health | Jackson, Michigan 49201 |
Sparrow Hospital | Lansing, Michigan 48912 |
Saint Mary Mercy Hospital | Livonia, Michigan 48154 |
Mercy Memorial Hospital | Monroe, Michigan 48162 |
Saint Joseph Mercy Oakland | Pontiac, Michigan 48341-2985 |
Saint Joseph Mercy Port Huron | Port Huron, Michigan 48060 |
Saint Mary's of Michigan | Saginaw, Michigan 48601 |
Lakeland Hospital | St. Joseph, Michigan 49085 |
Saint John Macomb-Oakland Hospital | Warren, Michigan 48093 |
Miller-Dwan Hospital | Duluth, Minnesota 55805 |
Unity Hospital | Fridley, Minnesota 55432 |
Saint John's Hospital - Healtheast | Maplewood, Minnesota 55109 |
Minnesota Oncology Hematology PA-Maplewood | Maplewood, Minnesota 55109 |
North Memorial Medical Health Center | Robbinsdale, Minnesota 55422 |
Park Nicollet Clinic - Saint Louis Park | Saint Louis Park, Minnesota 55416 |
Minnesota Oncology and Hematology PA-Woodbury | Woodbury, Minnesota 55125 |
Lincoln Medical Education Foundation Cancer Resource Center | Lincoln, Nebraska 68510 |
Missouri Valley Cancer Consortium CCOP | Omaha, Nebraska 68106 |
Nevada Cancer Research Foundation CCOP | Las Vegas, Nevada 89106 |
Hunterdon Medical Center | Flemington, New Jersey 08822 |
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County | Mount Holly, New Jersey 08060 |
Virtua West Jersey Hospital Voorhees | Voorhees, New Jersey 08043 |
Doctors Hospital | Columbus, Ohio 43228 |
Grant Medical Center | Columbus, Ohio 43215 |
Mount Carmel Health Center West | Columbus, Ohio 43222 |
Hematology Oncology Center Incorporated | Elyria, Ohio 44035 |
Marietta Memorial Hospital | Marietta, Ohio 45750 |
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center | Maumee, Ohio 43537 |
Saint Charles Hospital | Oregon, Ohio 43616 |
North Coast Cancer Care | Sandusky, Ohio 44870 |
Toledo Community Hospital Oncology Program CCOP | Toledo, Ohio 43617 |
Mercy Cancer Center at Saint Anne Mercy Hospital | Toledo, Ohio 43623 |
University of Toledo | Toledo, Ohio 43614 |
Saint Vincent Mercy Medical Center | Toledo, Ohio 43608 |
Saint Ann's Hospital | Westerville, Ohio 43081 |
Genesis HealthCare System | Zanesville, Ohio 43701 |
Natalie W Bryant Cancer Center | Tulsa, Oklahoma 74136 |
Pottstown Memorial Medical Center | Pottstown, Pennsylvania 19464 |
Scranton Hematology Oncology | Scranton, Pennsylvania 18510 |
Mercy Hospital | Scranton, Pennsylvania 18501 |
Geisinger Wyoming Valley | Wilkes-Barre, Pennsylvania 18711 |
Mainline Health CCOP | Wynnewood, Pennsylvania 19096 |
Fredericksburg Oncology Inc | Fredericksburg, Virginia 22401 |
Wheeling Hospital | Wheeling, West Virginia 26003 |
Saint Vincent Hospital | Green Bay, Wisconsin 54301 |
Green Bay Oncology Limited at Saint Mary's Hospital | Green Bay, Wisconsin 54303 |
Saint Mary's Hospital | Green Bay, Wisconsin 54303 |
Green Bay Oncology at Saint Vincent Hospital | Green Bay, Wisconsin 54301-3526 |
UW Health Oncology - 1 South Park | Madison, Wisconsin 53715 |
Bay Area Medical Center | Marinette, Wisconsin 54143 |
Marshfield Clinic-Minocqua Center | Minocqua, Wisconsin 54548 |
Green Bay Oncology - Oconto Falls | Oconto Falls, Wisconsin 54154 |
Marshfield Clinic at James Beck Cancer Center | Rhinelander, Wisconsin 54501 |
Marshfield Clinic-Rice Lake Center | Rice Lake, Wisconsin 54868 |
Green Bay Oncology - Sturgeon Bay | Sturgeon Bay, Wisconsin 54235 |
Marshfield Clinic-Wausau Center | Wausau, Wisconsin 54401 |
Illinois CancerCare-Bloomington | Bloomington%, Illinois 61701 |
Illinois CancerCare-Canton | Canton, Illinois 61520 |
Illinois CancerCare-Carthage | Carthage, Illinois 62321 |
Illinois CancerCare-Eureka | Eureka, Illinois 61530 |
Illinois CancerCare-Havana | Havana, Illinois 62644 |
Illinois CancerCare-Kewanee Clinic | Kewanee, Illinois 61443 |
Illinois CancerCare-Macomb | Macomb, Illinois 61455 |
Illinois CancerCare-Monmouth | Monmouth, Illinois 61462 |
Illinois CancerCare-Community Cancer Center | Normal, Illinois 61761 |
Illinois CancerCare-Pekin | Pekin, Illinois 61603 |
Illinois CancerCare-Peru | Peru, Illinois 61354 |
Illinois CancerCare-Princeton | Princeton, Illinois 61356 |
Illinois CancerCare-Spring Valley | Spring Valley, Illinois 61362 |
Cancer Center of Kansas-Liberal | Liberal, Kansas 67901 |
North Coast Cancer Care-Clyde | Clyde, Ohio 43410 |
Vanderbilt-Ingram Cancer Center Cool Springs | Franklin, Tennessee 37067 |
Nashville Oncology Associates PC | Nashville, Tennessee 37203 |
West Virginia University Charleston | Charleston, West Virginia 25304 |
Marshfield Clinic-Chippewa Center | Chippewa Falls, Wisconsin 54729 |
Holy Family Memorial Hospital | Manitowoc, Wisconsin 54221 |
Marshfield Clinic Cancer Care at Saint Michael's Hospital | Stevens Point, Wisconsin 54481 |
Riverview Hospital | Wisconsin Rapids, Wisconsin 54494 |
Hinsdale Hematology Oncology Associates Incorporated | Hinsdale, Illinois 60521 |
Spector, David MD (UIA Investigator) | Moline, Illinois 61265 |
UHHS-Chagrin Highlands Medical Center | Orange Village, Ohio 44122 |
UHHS-Westlake Medical Center | Westlake, Ohio 44145 |
Gundersen Lutheran | La Crosse, Wisconsin 54601 |
New York Oncology Hematology PC -Albany Medical Center | Albany, New York 12208 |
New York Oncology Hematology PC - Albany | Albany, New York 12206 |
New York Oncology Hematology PC - Amsterdam | Amsterdam, New York 12010 |
New York Oncology Hematology PC-Hudson | Hudson, New York 12534 |
New York Oncology Hematology PC - Latham | Latham, New York 12110 |
New York Oncology Hematology PC - Rexford | Rexford, New York 12148 |
New York Oncology Hematology PC - Troy | Troy, New York 12180 |
Stanford University Hospitals and Clinics | Stanford, California 94305 |
Siouxland Hematology Oncology Associates | Sioux City, Iowa 51101 |
IU Health Arnett | Lafayette, Indiana |
Oncology Associates at Mercy Medical Center | Cedar Rapids, Iowa 52403 |
Marie Yeager Cancer Center | Saint Joseph, Michigan 49085 |
Summa Akron City Hospital | Akron, Ohio 44304 |
The Toledo Hospital/Toledo Children's Hospital | Toledo, Ohio 43606 |
Genesys Regional Medical Center-West Flint Campus | Flint, Michigan 48532 |
Essentia Health Duluth Clinic CCOP | Duluth, Minnesota 55805 |
Essentia Health Saint Mary's Medical Center | Duluth, Minnesota 55805 |
Toledo Clinic Cancer Centers-Oregon | Oregon, Ohio 43616 |
Geisinger Medical Center-Cancer Center Hazelton | Hazleton, Pennsylvania 18201 |
Community Howard Regional Health | Kokomo, Indiana 46904 |
Indiana University Health La Porte Hospital | La Porte, Indiana 46350 |
Saint Joseph Regional Medical Center-Mishawaka | Mishawaka, Indiana 46545-1470 |
Springfield Regional Medical Center | Springfield, Ohio 45505 |
Toledo Clinic Cancer Centers-Bowling Green | Bowling Green, Ohio 43402 |
Toledo Clinic Cancer Centers-Maumee | Maumee, Ohio 43537-1839 |
Toledo Clinic Cancer Centers-Toledo | Toledo, Ohio 43623 |