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A Phase II Trial of Irinotecan and AZD2171 in Patients With Metastatic Colorectal Cancer After Progression on First-Line Oxaliplatin, Fluoropyrimidine, and Bevacizumab

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer

Thank you

Trial Information

A Phase II Trial of Irinotecan and AZD2171 in Patients With Metastatic Colorectal Cancer After Progression on First-Line Oxaliplatin, Fluoropyrimidine, and Bevacizumab



- 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

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.

Inclusion Criteria


- 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

- 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

- Patients who received treatment on CALGB-C80405 and whose treatment failed are
eligible for this study

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The proportion of patients who are progression-free at 12 weeks from the start of second-line therapy

Safety Issue:


Principal Investigator

Bert H. O'Neil, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

March 2008

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms



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