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Irinotecan and Cediranib in Treating Patients With Metastatic Colorectal Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2009
First Received: December 20, 2007   Last Updated: November 17, 2009   History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00588900
  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 giving irinotecan together with cediranib to see how well it works in treating patients with metastatic colorectal cancer.


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

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Trial of Irinotecan and AZD2171 in Patients With Metastatic Colorectal Cancer After Progression on FOLFOX Plus Cetuximab or FOLFOX Plus Bevacizumab and Cetuximab

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 within each cohort [ 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 ]
  • Comparison of the efficacy of the combination of irinotecan hydrochloride and cediranib among patients naïve to bevacizumab versus those previously treated with bevacizumab [ Designated as safety issue: No ]

Estimated Enrollment: 88
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 for each of the two cohorts.

Secondary

  • To determine objective response rate for each treatment cohort.
  • To determine overall survival for the patients treated in each cohort.
  • To further define the dosing and safety profile of irinotecan hydrochloride and cediranib.

OUTLINE: Patients are stratified according to prior therapy (oxaliplatin-based therapy with cetuximab [cohort A] vs oxaliplatin-based therapy with cetuximab and bevacizumab [cohort B]).

Patients receive irinotecan hydrochloride IV over 90 minutes on days 1 and 8 and oral cediranib 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 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

    • 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:

      • 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
  • The site of the primary lesion must be or have been confirmed endoscopically, surgically, or radiologically to have been in the colon or rectum
  • 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

    • For Cohort A, prior therapy should consist of oxaliplatin plus a fluoropyrimidine and cetuximab without bevacizumab
    • Cohort B will consist of patients previously treated with oxaliplatin, a fluoropyrimidine, cetuximab and 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 (unless increase is felt to be secondary to tumor burden)
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00588900

Locations
United States, Illinois
Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201-1781
Contact: Clinical Trials Office - Evanston Hospital     847-570-1381        
United States, Indiana
CCOP - Northern Indiana CR Consortium Recruiting
South Bend, Indiana, United States, 46601
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
Center for Cancer Therapy at LaPorte Hospital and Health Services Recruiting
La Porte, Indiana, United States, 46350
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
Memorial Hospital of South Bend Recruiting
South Bend, Indiana, United States, 46601
Contact: Clinical Trials Office - Memorial Hospital of South Bend     800-284-7370        
Howard Community Hospital Recruiting
Kokomo, Indiana, United States, 46904
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
Elkhart General Hospital Recruiting
Elkhart, Indiana, United States, 46515
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
Saint Joseph Regional Medical Center Recruiting
South Bend, Indiana, United States, 46617
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
South Bend Clinic Recruiting
South Bend, Indiana, United States, 46617
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
United States, Iowa
Hematology Oncology Associates of the Quad Cities Recruiting
Bettendorf, Iowa, United States, 52722
Contact: Shobha R. Chitneni, MD, MBBS     563-355-7733        
United States, Michigan
Lakeland Regional Cancer Care Center - St. Joseph Recruiting
St. Joseph, Michigan, United States, 49085
Contact: Rafat H. Ansari, MD, FACP     574-234-5123        
Oncology Care Associates, PLLC Recruiting
Saint Joseph, Michigan, United States, 49085
Contact: Eric P. Lester, MD     269-985-0029        
United States, Missouri
Arch Medical Services, Incorporated at Center for Cancer Care and Research Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Alan P. Lyss, MD     314-996-5514        
Ellis Fischel Cancer Center at University of Missouri - Columbia Recruiting
Columbia, Missouri, United States, 65203
Contact: Clinical Trial Office - Ellis Fischel Cancer Center     573-882-7440        
Missouri Baptist Cancer Center Recruiting
Saint Louis, Missouri, United States, 63131
Contact: Alan P. Lyss, MD     314-996-5514        
United States, Nebraska
Alegant Health Cancer Center at Bergan Mercy Medical Center Recruiting
Omaha, Nebraska, United States, 68124
Contact: Clinical Trials Office - Alegant Health Cancer Center at Berge     402-398-6060        
Cancer Resource Center - Lincoln Recruiting
Lincoln, Nebraska, United States, 68510
Contact: Alan R. Berg, MD     402-420-7000        
Immanuel Medical Center Recruiting
Omaha, Nebraska, United States, 68122
Contact: Gamini S. Soori, MD, FACP, FRCP, MBA     402-393-3110        
Creighton University Medical Center Recruiting
Omaha, Nebraska, United States, 68131-2197
Contact: Clinical Trials Office - Creighton University Medical Center     402-280-4100        
CCOP - Missouri Valley Cancer Consortium Recruiting
Omaha, Nebraska, United States, 68106
Contact: Gamini S. Soori, MD, FACP, FRCP, MBA     402-393-3110        
United States, New York
CCOP - Hematology-Oncology Associates of Central New York Recruiting
East Syracuse, New York, United States, 13057
Contact: Jeffrey J. Kirshner, MD     315-472-7504        
United States, North Carolina
Kinston Medical Specialists Recruiting
Kinston, North Carolina, United States, 28501
Contact: Peter R. Watson, MD     252-559-2200ext.201        
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Clinical Trials Office - Lineberger Comprehensive Cancer Cente     877-668-0683; 919-966-4432        
Rex Cancer Center at Rex Hospital Recruiting
Raleigh, North Carolina, United States, 27607
Contact: Clinical Trials Office - Rex Cancer Center     919-784-7209        
Wake Forest University Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive     336-713-6771        
Wayne Memorial Hospital, Incorporated Recruiting
Goldsboro, North Carolina, United States, 27534
Contact: James N. Atkins, MD     919-580-0000        
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: Cancer and Leukemia Group B ( Richard L. Schilsky )
Study ID Numbers: CDR0000580967, CALGB-80502
Study First Received: December 20, 2007
Last Updated: November 17, 2009
ClinicalTrials.gov Identifier: NCT00588900     History of Changes
Health Authority: Unspecified

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:
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Colonic Diseases
Irinotecan
Enzyme Inhibitors
Intestinal Diseases
Rectal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Camptothecin
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Gastrointestinal Neoplasms
Antineoplastic Agents, Phytogenic
Colorectal Neoplasms

ClinicalTrials.gov processed this record on November 20, 2009