Irinotecan and Cediranib in Treating Patients With Metastatic Colorectal Cancer That Did Not Respond to Previous Oxaliplatin, Fluoropyrimidine, and Bevacizumab

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00588900
First received: December 20, 2007
Last updated: February 24, 2011
Last verified: February 2011
  Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving irinotecan together with cediranib may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying how well giving irinotecan together with cediranib works in treating patients with metastatic colorectal cancer that did not respond to previous oxaliplatin, fluoropyrimidine, and bevacizumab.


Condition Intervention Phase
Colorectal Cancer
Drug: cediranib maleate
Drug: irinotecan hydrochloride
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Irinotecan and AZD2171 in Patients With Metastatic Colorectal Cancer After Progression on First-Line Oxaliplatin, Fluoropyrimidine, and Bevacizumab

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • The proportion of patients who are progression-free at 12 weeks from the start of second-line therapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic response rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]

Estimated Enrollment: 48
Study Start Date: March 2008
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the proportion of patients who are free from progression at 12 weeks from the start of second-line therapy.

Secondary

  • To determine objective response rate.
  • To determine overall survival.
  • To further define the dosing and safety profile of irinotecan hydrochloride and cediranib.

OUTLINE: This is a multicenter study.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588900

Locations
United States, Illinois
Evanston Hospital
Evanston, Illinois, United States, 60201-1781
United States, Indiana
Elkhart Clinic, LLC
Elkhart, Indiana, United States, 46514-2098
Elkhart General Hospital
Elkhart, Indiana, United States, 46515
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46845
Howard Community Hospital
Kokomo, Indiana, United States, 46904
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, United States, 46350
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
Michiana Hematology-Oncology, PC - South Bend
South Bend, Indiana, United States, 46601
Saint Joseph Regional Medical Center
South Bend, Indiana, United States, 46617
South Bend Clinic
South Bend, Indiana, United States, 46617
United States, Iowa
Hematology Oncology Associates of the Quad Cities
Bettendorf, Iowa, United States, 52722
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Michigan
Lakeside Cancer Specialists, PLLC
Saint Joseph, Michigan, United States, 49085
Lakeland Regional Cancer Care Center - St. Joseph
St. Joseph, Michigan, United States, 49085
United States, Missouri
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
United States, Nebraska
Cancer Resource Center - Lincoln
Lincoln, Nebraska, United States, 68510
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, United States, 68124
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
Creighton University Medical Center
Omaha, Nebraska, United States, 68131-2197
Immanuel Medical Center
Omaha, Nebraska, United States, 68122
United States, New Hampshire
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
Concord, New Hampshire, United States, 03301
New Hampshire Oncology - Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
Lakes Region General Hospital
Laconia, New Hampshire, United States, 03246
United States, New York
CCOP - Hematology-Oncology Associates of Central New York
East Syracuse, New York, United States, 13057
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
Rex Cancer Center at Rex Hospital
Raleigh, North Carolina, United States, 27607
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Bert H. O'Neil, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00588900     History of Changes
Other Study ID Numbers: CDR0000580967, CALGB-80502
Study First Received: December 20, 2007
Last Updated: February 24, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Maleic acid
Irinotecan
Camptothecin
Cediranib
Oxaliplatin
Bevacizumab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014