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

NCT00588900 | Terminated Phase 2 Results

• 2 other identifiers: CALGB-80502CDR0000580967
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 31

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.

Conditions

Colorectal Cancer

Keywords

stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Outcome Measures

Primary Outcomes (1)

• The Percentage of Patients Who Are Progression-free at 12 Weeks From the Start of Second-line Therapy

  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.

  at 12 weeks

Secondary Outcomes (2)

• Radiographic Response Rate

  Up to 2 years

• Overall Survival

  Up to 2 years

Study Arms (1)

irinotecan + cediranib

EXPERIMENTAL

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

Interventions

cediranib maleate DRUG

irinotecan + cediranib

irinotecan hydrochloride DRUG

irinotecan + cediranib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (31)

Evanston Hospital

Evanston, Illinois, 60201-1781, United States

Location

Elkhart Clinic, LLC

Elkhart, Indiana, 46514-2098, United States

Location

Elkhart General Hospital

Elkhart, Indiana, 46515, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46845, United States

Location

Howard Community Hospital

Kokomo, Indiana, 46904, United States

Location

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, 46350, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Michiana Hematology-Oncology, PC - South Bend

South Bend, Indiana, 46601, United States

Location

Saint Joseph Regional Medical Center

South Bend, Indiana, 46617, United States

Location

South Bend Clinic

South Bend, Indiana, 46617, United States

Location

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, 52722, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Lakeside Cancer Specialists, PLLC

Saint Joseph, Michigan, 49085, United States

Location

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, 65203, United States

Location

Cancer Resource Center - Lincoln

Lincoln, Nebraska, 68510, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Immanuel Medical Center

Omaha, Nebraska, 68122, United States

Location

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, 68124, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131-2197, United States

Location

New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care

Concord, New Hampshire, 03301, United States

Location

New Hampshire Oncology - Hematology, PA - Hooksett

Hooksett, New Hampshire, 03106, United States

Location

Lakes Region General Hospital

Laconia, New Hampshire, 03246, United States

Location

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, 13057, United States

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, 27534, United States

Location

Kinston Medical Specialists

Kinston, North Carolina, 28501, United States

Location

Rex Cancer Center at Rex Hospital

Raleigh, North Carolina, 27607, United States

Location

Iredell Memorial Hospital

Statesville, North Carolina, 28677, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

cediranib; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Bert O'Neil, M.D.
• Organization: UNC Lineberger Comprehensive Cancer Center

bert_oneil@med.unc.edu

Study Officials

• Bert H. O'Neil, MD

  UNC Lineberger Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: January 9, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: November 1, 2011
• Last Updated: April 5, 2017
• Results First Posted: March 3, 2017

Record last verified: 2017-03

Locations

US (31)