Irinotecan and Cediranib in Treating Patients With Metastatic Colorectal Cancer That Did Not Respond to Previous Oxaliplatin, Fluoropyrimidine, and Bevacizumab
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically documented metastatic colorectal cancer
- The site of the primary lesion must be or have been confirmed endoscopically, surgically, or radiologically to have been in the colon or rectum
Patients with a history of histologically proven colorectal cancer treated by surgical resection and who develop radiological or clinical evidence of metastatic cancer do not require additional histological or cytological confirmation of metastatic disease unless either of the following are true:
- An interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease
- The primary cancer was stage I
Must have measurable disease, defined as in at least one dimension (longest dimension to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
Lesions that are considered nonmeasurable include the following:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
Must have received one and only one prior regimen for metastatic disease containing oxaliplatin, a fluoropyrimidine, and bevacizumab
- Patients who discontinue oxaliplatin due to toxicity are eligible provided they progressed on the fluoropyrimidine component with or without bevacizumab
- No known brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 8 g/dL
- Leukocytes ≥ 3,000/mm³
- Calculated creatinine clearance > 50 mL/min
- ALT/AST ≤ 2.5 times upper limit of normal (ULN)
- Urine protein < 1+ protein OR protein < 1g by 24-hour urine collection and urine protein:creatinine ratio < 1.0
- Total bilirubin normal
- Not pregnant or nursing
- Negative pregnancy test
- No known end-stage liver disease or active hepatitis
No colonic or small bowel disorders (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis) that predispose to diarrhea in which the symptoms are uncontrolled as indicated by baseline pattern of > 3 watery or soft stools daily in patients without a colostomy or ileostomy
- Patients with a colostomy or ileostomy may be entered at investigator discretion
- History of hypertension allowed provided it is well controlled (BP < 150/90 mm Hg) on a regimen of antihypertensive therapy
- No concurrent congestive heart failure (New York Heart Association class III or IV)
No significant history of bleeding events or gastrointestinal (GI) perforation
- Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 3 months prior to beginning treatment are not eligible unless the source of bleeding has been surgically resected
- Patients with a history of GI perforation within 12 months prior to beginning treatment are not eligible
No arterial thrombotic events within 6 months before beginning treatment, including any of the following:
- Transient ischemic attack
- Cerebrovascular accident
- Unstable angina or angina requiring surgical or medical intervention within the past 6 months
- Myocardial infarction
- No serious or nonhealing wound, ulcer, or bone fracture
- Patients with clinically significant peripheral artery disease (i.e., claudication on ambulating less than one block) or any other arterial thrombotic event within 6 months are also ineligible
- QTc interval ≤ 470 msec
- No personal or family history of long QT syndrome.
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Must have recovered from all acute toxicities of prior therapy for metastatic disease except peripheral neuropathy
- At least 6 weeks between the last dose of bevacizumab and the first dose of cediranib
- Prior pelvic irradiation is allowed (as long as the measurable lesion is outside the radiotherapy field)
Completed any major surgery ≥ 4 weeks from start of treatment and completed any minor surgery ≥ 1 week prior to start of treatment
- Insertion of a vascular access device is not considered major or minor surgery from the standpoint of protocol eligibility
- Patients must have fully recovered from the procedure and have a fully healed incision
Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both of the following criteria are met:
- The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or is on a stable dose of low molecular weight heparin
- The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- Patients receiving anti-platelet agents are eligible
- Patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible
- The use of agents with strong proarrhythmic potential is not permitted during the study
- Patients who received treatment on CALGB-C80405 and whose treatment failed are eligible for this study
Sites / Locations
- Evanston Hospital
- Elkhart Clinic, LLC
- Elkhart General Hospital
- Fort Wayne Medical Oncology and Hematology
- Howard Community Hospital
- Center for Cancer Therapy at LaPorte Hospital and Health Services
- CCOP - Northern Indiana CR Consortium
- Memorial Hospital of South Bend
- Michiana Hematology-Oncology, PC - South Bend
- Saint Joseph Regional Medical Center
- South Bend Clinic
- Hematology Oncology Associates of the Quad Cities
- Holden Comprehensive Cancer Center at University of Iowa
- Lakeside Cancer Specialists, PLLC
- Lakeland Regional Cancer Care Center - St. Joseph
- Ellis Fischel Cancer Center at University of Missouri - Columbia
- Cancer Resource Center - Lincoln
- CCOP - Missouri Valley Cancer Consortium
- Immanuel Medical Center
- Alegant Health Cancer Center at Bergan Mercy Medical Center
- Creighton University Medical Center
- New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
- New Hampshire Oncology - Hematology, PA - Hooksett
- Lakes Region General Hospital
- CCOP - Hematology-Oncology Associates of Central New York
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
- Wayne Memorial Hospital, Incorporated
- Kinston Medical Specialists
- Rex Cancer Center at Rex Hospital
- Iredell Memorial Hospital
- Wake Forest University Comprehensive Cancer Center
Arms of the Study
Arm 1
Experimental
irinotecan + cediranib
Patients receive irinotecan hydrochloride IV over 90 minutes on days 1 and 8 and oral cediranib once daily on days 1-21. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for up to 2 years from study entry.