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
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring mucinous adenocarcinoma of the colon, recurrent colon cancer, signet ring adenocarcinoma of the colon, stage III colon cancer, stage IV colon cancer, mucinous adenocarcinoma of the rectum, recurrent rectal cancer, signet ring adenocarcinoma of the rectum, stage III rectal cancer, stage IV rectal cancer
Eligibility Criteria
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
Sites / Locations
- UAB Comprehensive Cancer Center
- Aurora Presbyterian Hospital
- Boulder Community Hospital
- Penrose Cancer Center at Penrose Hospital
- St. Anthony Central Hospital
- Porter Adventist Hospital
- Presbyterian - St. Luke's Medical Center
- St. Joseph Hospital
- Rose Medical Center
- CCOP - Colorado Cancer Research Program
- Swedish Medical Center
- Poudre Valley Hospital
- Front Range Cancer Specialists
- St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
- North Colorado Medical Center
- Littleton Adventist Hospital
- Sky Ridge Medical Center
- Hope Cancer Care Center at Longmont United Hospital
- McKee Medical Center
- Parker Adventist Hospital
- St. Mary - Corwin Regional Medical Center
- North Suburban Medical Center
- Exempla Lutheran Medical Center
- Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
- Yale Cancer Center
- Veterans Affairs Medical Center - Atlanta (Decatur)
- Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
- Rush-Copley Cancer Care Center
- St. Joseph Medical Center
- Graham Hospital
- Memorial Hospital
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
- Hematology and Oncology Associates
- John H. Stroger, Jr. Hospital of Cook County
- Decatur Memorial Hospital Cancer Care Institute
- Eureka Community Hospital
- Galesburg Clinic, PC
- Mason District Hospital
- Kellogg Cancer Care Center
- Hinsdale Hematology Oncology Associates
- Provena St. Mary's Regional Cancer Center - Kankakee
- North Shore Oncology and Hematology Associates, Limited - Libertyville
- McDonough District Hospital
- Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
- Cancer Care and Hematology Specialists of Chicagoland - Niles
- BroMenn Regional Medical Center
- Community Cancer Center
- Advocate Christ Medical Center
- Community Hospital of Ottawa
- Cancer Treatment Center at Pekin Hospital
- Proctor Hospital
- CCOP - Illinois Oncology Research Association
- Oncology Hematology Associates of Central Illinois, PC - Peoria
- Methodist Medical Center of Illinois
- OSF St. Francis Medical Center
- Illinois Valley Community Hospital
- Perry Memorial Hospital
- West Suburban Center for Cancer Care
- Swedish-American Regional Cancer Center
- Hematology Oncology Associates - Skokie
- Regional Cancer Center at Memorial Medical Center
- CCOP - Carle Cancer Center
- Indiana University Melvin and Bren Simon Cancer Center
- William N. Wishard Memorial Hospital
- Clarian Arnett Cancer Care
- Saint Anthony Memorial Health Centers
- McFarland Clinic, PC
- Cedar Rapids Oncology Associates
- Mercy Regional Cancer Center at Mercy Medical Center
- Medical Oncology and Hematology Associates - West Des Moines
- CCOP - Iowa Oncology Research Association
- John Stoddard Cancer Center at Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates at John Stoddard Cancer Center
- Medical Oncology and Hematology Associates at Mercy Cancer Center
- Mercy Cancer Center at Mercy Medical Center - Des Moines
- John Stoddard Cancer Center at Iowa Lutheran Hospital
- Mercy Cancer Center at Mercy Medical Center - North Iowa
- McCreery Cancer Center at Ottumwa Regional
- Siouxland Hematology-Oncology Associates, LLP
- Mercy Medical Center - Sioux City
- St. Luke's Regional Medical Center
- Cancer Center of Kansas, PA - Chanute
- Cancer Center of Kansas, PA - Dodge City
- Cancer Center of Kansas, PA - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas, PA - Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas, PA - Liberal
- Cancer Center of Kansas, PA - McPherson
- Cancer Center of Kansas, PA - Newton
- Cancer Center of Kansas, PA - Parsons
- Cancer Center of Kansas, PA - Pratt
- Cancer Center of Kansas, PA - Salina
- Cancer Center of Kansas, PA - Wellington
- Associates in Womens Health, PA - North Review
- Cancer Center of Kansas, PA - Medical Arts Tower
- Cancer Center of Kansas, PA - Wichita
- CCOP - Wichita
- Via Christi Cancer Center at Via Christi Regional Medical Center
- Cancer Center of Kansas, PA - Winfield
- Mary Bird Perkins Cancer Center - Baton Rouge
- Ochsner Health Center - Bluebonnet
- Ochsner Health Center - Covington
- MBCCOP - LSU Health Sciences Center
- Medical Center of Louisiana - New Orleans
- Ochsner Cancer Institute at Ochsner Clinic Foundation
- Greater Baltimore Medical Center Cancer Center
- Baystate Regional Cancer Program at D'Amour Center for Cancer Care
- Hickman Cancer Center at Bixby Medical Center
- Saint Joseph Mercy Cancer Center
- CCOP - Michigan Cancer Research Consortium
- Oakwood Cancer Center at Oakwood Hospital and Medical Center
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Van Elslander Cancer Center at St. John Hospital and Medical Center
- Foote Memorial Hospital
- Borgess Medical Center
- West Michigan Cancer Center
- Bronson Methodist Hospital
- Sparrow Regional Cancer Center
- St. Mary Mercy Hospital
- Community Cancer Center of Monroe
- Mercy Memorial Hospital - Monroe
- St. Joseph Mercy Oakland
- Mercy Regional Cancer Center at Mercy Hospital
- Seton Cancer Institute at Saint Mary's - Saginaw
- St. John Macomb Hospital
- MeritCare Bemidji
- Fairview Ridges Hospital
- Mercy and Unity Cancer Center at Mercy Hospital
- Duluth Clinic Cancer Center - Duluth
- CCOP - Duluth
- Miller - Dwan Medical Center
- Fairview Southdale Hospital
- Mercy and Unity Cancer Center at Unity Hospital
- Hutchinson Area Health Care
- HealthEast Cancer Care at St. John's Hospital
- Minnesota Oncology - Maplewood
- Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
- Hennepin County Medical Center - Minneapolis
- New Ulm Medical Center
- Humphrey Cancer Center at North Memorial Outpatient Center
- CCOP - Metro-Minnesota
- Park Nicollet Cancer Center
- Regions Hospital Cancer Care Center
- United Hospital
- St. Francis Cancer Center at St. Francis Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Willmar Cancer Center at Rice Memorial Hospital
- Minnesota Oncology - Woodbury
- Cancer Resource Center - Lincoln
- CCOP - Missouri Valley Cancer Consortium
- Immanuel Medical Center
- Alegant Health Cancer Center at Bergan Mercy Medical Center
- Lakeside Hospital
- Creighton University Medical Center
- Veterans Affairs Medical Center - East Orange
- Hunterdon Regional Cancer Center at Hunterdon Medical Center
- CentraState Medical Center
- Hematology Oncology Associates, PC
- Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital
- University of New Mexico Cancer Center
- New Mexico Cancer Care Associates
- NYU Cancer Institute at New York University Medical Center
- CCOP - MeritCare Hospital
- Roger Maris Cancer Center at MeritCare Hospital
- Summa Center for Cancer Care at Akron City Hospital
- Wood County Oncology Center
- Adena Regional Medical Center
- Case Comprehensive Cancer Center
- MetroHealth Cancer Care Center at MetroHealth Medical Center
- Riverside Methodist Hospital Cancer Care
- CCOP - Columbus
- Grant Medical Center Cancer Care
- Mount Carmel Health - West Hospital
- Doctors Hospital at Ohio Health
- Grady Memorial Hospital
- Community Cancer Center
- Hematology Oncology Center
- Fairfield Medical Center
- St. Rita's Medical Center
- Lima Memorial Hospital
- Strecker Cancer Center at Marietta Memorial Hospital
- Northwest Ohio Oncology Center
- Knox Community Hospital
- Licking Memorial Cancer Care Program at Licking Memorial Hospital
- St. Charles Mercy Hospital
- Toledo Clinic - Oregon
- North Coast Cancer Care, Incorporated
- Community Hospital of Springfield and Clark County
- Flower Hospital Cancer Center
- Mercy Hospital of Tiffin
- Toledo Hospital
- St. Vincent Mercy Medical Center
- Medical University of Ohio Cancer Center
- CCOP - Toledo Community Hospital
- St. Anne Mercy Hospital
- Toledo Clinic, Incorporated - Main Clinic
- Fulton County Health Center
- Mount Carmel St. Ann's Cancer Center
- Genesis - Good Samaritan Hospital
- Natalie Warren Bryant Cancer Center at St. Francis Hospital
- St. Luke's Cancer Network at St. Luke's Hospital
- Bryn Mawr Hospital
- Geisinger Cancer Institute at Geisinger Health
- Doylestown Hospital Cancer Center
- PinnacleHealth Regional Cancer Center at Polyclinic Hospital
- Geisinger Hazleton Cancer Center
- Cancer Center of Paoli Memorial Hospital
- Abramson Cancer Center of the University of Pennsylvania
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
- Joan Karnell Cancer Center at Pennsylvania Hospital
- Fox Chase Cancer Center - Philadelphia
- Pottstown Memorial Regional Cancer Center
- McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
- Hematology and Oncology Associates of Northeastern Pennsylvania
- Grand View Hospital
- Geisinger Medical Group - Scenery Park
- Chester County Hospital
- Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
- CCOP - Main Line Health
- Lankenau Cancer Center at Lankenau Hospital
- Sanford Cancer Center at Sanford USD Medical Center
- Parkland Memorial Hospital
- Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
- CCOP - Scott and White Hospital
- Fredericksburg Oncology, Incorporated
- West Virginia University Health Sciences Center - Charleston
- Langlade Memorial Hospital
- Marshfield Clinic Cancer Care at Regional Cancer Center
- St. Vincent Hospital Regional Cancer Center
- Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center
- UW Cancer Center Johnson Creek
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
- Holy Family Memorial Medical Center Cancer Care Center
- Bay Area Cancer Care Center at Bay Area Medical Center
- Vince Lombardi Cancer Clinic - Marinette
- Marshfield Clinic - Marshfield Center
- Marshfield Clinic - Lakeland Center
- Regional Cancer Center at Oconomowoc Memorial Hospital
- Ministry Medical Group at Saint Mary's Hospital
- Marshfield Clinic - Indianhead Center
- St. Nicholas Hospital
- Vince Lombardi Cancer Clinic - Sheboygan
- Marshfield Clinic at Saint Michael's Hospital
- Aurora Medical Center
- Vince Lombardi Cancer Clinic - Two Rivers
- Waukesha Memorial Hospital Regional Cancer Center
- University of Wisconcin Cancer Center at Aspirus Wausau Hospital
- Diagnostic and Treatment Center
- Marshfield Clinic - Weston Center
- Marshfield Clinic - Wisconsin Rapids Center
- Riverview UW Cancer Center at Riverview Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Arm A (IC)
Arm B (ICR)
Arm C (mICR)
Patients receive cetuximab (500 mg/m2) intravenously (IV) over 60-120 minutes and irinotecan hydrochloride (180 mg/m2) over 60-90 minutes on day 1. Treatment repeats every 2 weeks until disease progression or unacceptable toxicities.
Patients receive ramucirumab (8 mg/kg) IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm A. Treatment repeats every 2 weeks until disease progression or unacceptable toxicities.
Patients receive reduced dose of ramucirumab (6 mg/kg) IV over 60 minutes on day 1 and cetuximab (150 mg/m2) and irinotecan hydrochloride (400 mg/m2) as in arm B. Treatment repeats every 2 weeks until disease progression or unacceptable toxicities.