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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00588900
Recruitment Status : Terminated
First Posted : January 9, 2008
Results First Posted : March 3, 2017
Last Update Posted : April 5, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief Summary:

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 or disease Intervention/treatment Phase
Colorectal Cancer Drug: cediranib maleate Drug: irinotecan hydrochloride Phase 2

Detailed Description:



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


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : March 2008
Actual Primary Completion Date : May 2010
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Drug: cediranib maleate
Drug: irinotecan hydrochloride

Primary Outcome Measures :
  1. The Percentage of Patients Who Are Progression-free at 12 Weeks From the Start of Second-line Therapy [ Time Frame: at 12 weeks ]
    The 12 week progression-free rate was defined as the percentage of patients that were alive and progression-free 12 weeks after start of second-line therapy. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions.

Secondary Outcome Measures :
  1. Radiographic Response Rate [ Time Frame: Up to 2 years ]

    The proportion of patients who respond (completely or partially) to each combination regimen will be estimated.

    Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.

  2. Overall Survival [ Time Frame: Up to 2 years ]
    Overall Survival (OS) is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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.


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00588900

Show Show 31 study locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
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Study Chair: Bert H. O'Neil, MD UNC Lineberger Comprehensive Cancer Center
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Responsible Party: Alliance for Clinical Trials in Oncology Identifier: NCT00588900    
Other Study ID Numbers: CALGB-80502
CDR0000580967 ( Registry Identifier: NCI Physician Data Query )
First Posted: January 9, 2008    Key Record Dates
Results First Posted: March 3, 2017
Last Update Posted: April 5, 2017
Last Verified: March 2017
Keywords provided by Alliance for Clinical Trials in Oncology:
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors