Clinical trial NCT00588900: Irinotecan and Cediranib in Treating Patients With Metastatic Colorectal Cancer That Did Not Respond to Previous Oxaliplatin, Fluoropyrimidine, and Bevacizumab
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-01-09
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: The Percentage of Patients Who Are Progression-free at 12 Weeks From the Start of Second-line Therapy
timeFrame: at 12 weeks
Secondary outcomes:
measure: Radiographic Response Rate
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic, LLC
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology-Oncology, PC - South Bend
state: Indiana
city: South Bend
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: South Bend
country: United States
facility: South Bend Clinic
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: St. Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Concord
country: United States
facility: New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology - Hematology, PA - Hooksett
state: New Hampshire
city: Laconia
country: United States
facility: Lakes Region General Hospital
state: New Hampshire
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center at Rex Hospital
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Bert H. O'Neil, MD
role: STUDY_CHAIR
References: