Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy

Colorectal Cancer Clinical Trial

Official title:

A Randomized Phase II Study of Irinotecan and Cetuximab With or Without the Anti-Angiogenic Antibody, Ramucirumab (IMC-1121B), in Advanced, K-ras Wild-Type Colorectal Cancer Following Progression on Bevacizumab-Containing Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01079780
• Other study ID #: E7208
• Secondary ID: CDR0000666736
• Status: Completed
• Phase: Phase 2
• Start date: January 18, 2011
• 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 irinotecan hydrochloride, 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 cetuximab and ramucirumab, 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. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with advanced colorectal cancer with progressive disease after treatment with bevacizumab-containing chemotherapy.

Description:

OBJECTIVES:

• To evaluate the progression-free survival of patients with advanced K-ras wild-type colorectal cancer, following progression on bevacizumab-contained chemotherapy, treated with irinotecan hydrochloride and cetuximab with versus without ramucirumab as second-line therapy.

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

• To evaluate the grade 3-4 toxicity rates of these regimens in these patients.

• To evaluate the overall survival of patients treated with these regimens.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), discontinuation of oxaliplatin before disease progression (yes vs no), and time to disease progression since last treatment (≤ 6 months vs > 6 months). Patients are randomized to 1 of 2 treatment arms.

• Arm A: Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride over 60-90 minutes on day 1.

• Arm B: Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm A. Arm B was closed early due to excessive toxicities and Arm C was then added to the study with reduced dose of protocol drugs.

• Arm C: Patients receive reduced dose of ramucirumab, cetuximab and irinotecan hydrochloride as in arm B.

In all arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up periodically for 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: August 17, 2021
• Est. primary completion date: February 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Measurable disease

• Histologically confirmed adenocarcinoma of the colon or rectum

• K-ras wild type based on either primary or metastatic tumor

• Must have received prior first-line therapy comprising oxaliplatin-based fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal cancer

• Registration within 42 days since confirmed disease progression

• Performance status 0-1

• ANC = 1,500/µL

• Platelet count = 75,000/µL

• Hemoglobin = 9 g/dL

• Serum creatinine = 1.5 times upper limit of normal (ULN) OR creatinine clearance = 40 mL/min

• Urine protein = 1+ on dipstick or routine urinalysis (if = 2+, a 24-hour urine collection must demonstrate < 1,000 mg of protein)

• Total bilirubin = 2.0 mg/dL

• AST and ALT = 3.0 times ULN (5.0 times ULN for patients with liver metastases)

• INR = 1.6 (= 3.0 for patients on warfarin and no active bleeding [i.e., no bleeding within the past 14 days])

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study therapy

• At least 28 days and no more than 90 days since prior bevacizumab

• Concurrent stable dose of oral anticoagulant or low-molecular weight heparin allowed

Exclusion Criteria:

• Brain or CNS metastases

• Pregnant or nursing

• Prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for colorectal cancer

• Clinically significant (equivalent to NCI CTCAE grade 3-4) bleeding episodes within the past 3 months

• Active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Symptomatic or poorly controlled cardiac arrhythmia

• Uncontrolled thrombotic or hemorrhagic disorder

• Uncontrolled or poorly controlled hypertension despite standard medical management (e.g., consistently systolic BP > 160 mm Hg and diastolic BP > 90 mm Hg)

• Acute arterial thrombotic events within the past 6 months, including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina

• Other cancer requiring therapy within the past 3 years except in situ carcinoma or nonmelanoma skin cancer

• Acute or subacute intestinal obstruction

• History of inflammatory bowel disease requiring pharmacological and/or surgical intervention within the past 12 months

• Known allergy to any of the treatment components

• Major surgery within the past 28 days

• Subcutaneous venous access device placement within the past 7 days

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• cetuximab
Given IV
• ramucirumab
Given IV

Drug:
• irinotecan hydrochloride
Given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Hematology Oncology Associates, PC	Albuquerque	New Mexico
United States	Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Langlade Memorial Hospital	Antigo	Wisconsin
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Case Comprehensive 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	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Ochsner Health Center - Covington	Covington	Louisiana
United States	Parkland Memorial Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Colorado Cancer Research Program	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	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Doylestown Hospital Cancer Center	Doylestown	Pennsylvania
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	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Roger Maris Cancer Center at MeritCare Hospital	Fargo	North Dakota
United States	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey
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	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	CentraState Medical Center	Freehold	New Jersey
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
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	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	PinnacleHealth Regional Cancer Center at Polyclinic Hospital	Harrisburg	Pennsylvania
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	Foote Memorial Hospital	Jackson	Michigan
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Clarian Arnett Cancer Care	Lafayette	Indiana
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
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	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	McDonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
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	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Yale Cancer Center	New Haven	Connecticut
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Medical Center of Louisiana - New Orleans	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	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
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	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
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	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
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	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania
United States	Grand View Hospital	Sellersville	Pennsylvania
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	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	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Aurora Medical Center	Summit	Wisconsin
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	CCOP - Scott and White Hospital	Temple	Texas
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	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
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	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progression-fee survival is defined as the time from randomization to disease progression or death without documentation of progression. Censoring occurred at the date of last disease assessment without progression for cases without documentation of progression, except for cases where death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was considered an event.; Progression is defined as appearance of one or more new lesions and/or 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 study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
Secondary	Proportion of Participants With an Objective Response Rate (CR or PR)	Objective response is defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
Secondary	Proportion of Patients With Grade 3 or Higher Treatment-related Adverse Events	Adverse events were assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE). Treatment-related adverse events are defined as those that are possibly, probably, or definitely related to protocol therapy.	Assessed every 2 weeks while on treatment and for 30 days after the end of treatment
Secondary	Overall Survival	Overall survival is defined as the time from randomization to death or date last known alive.	Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years