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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00588900
• Other study ID #: CALGB-80502
• Secondary ID: CALGB-80502CDR00
• Status: Terminated
• Phase: Phase 2
• First received: December 20, 2007
• Last updated: December 9, 2016
• Start date: March 2008
• Est. completion date: November 2011

Study information

• Verified date: December 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: November 2011
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• cediranib maleate

• irinotecan hydrochloride

Locations

Country	Name	City	State
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Elkhart Clinic, LLC	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Evanston Hospital	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lakes Region General Hospital	Laconia	New Hampshire
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology-Oncology, PC - South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients who are progression-free at 12 weeks from the start of second-line therapy		at 12 weeks	No
Secondary	Radiographic response rate		Up to 2 years	No
Secondary	Overall survival		Up to 2 years	No