Cetuximab and Irinotecan in Treating Patients With Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00005076
First received: April 6, 2000
Last updated: April 10, 2013
Last verified: April 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as cetuximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of cetuximab and irinotecan in treating patients who have advanced colorectal cancer that has not responded to previous treatment.


Condition Intervention Phase
Colorectal Cancer
Biological: cetuximab
Drug: irinotecan hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Anti-Epidermal Growth Factor Receptor (EGFr) Antibody Cetuximab in Combination With Chemotherapy in Patients With Advanced Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Determine the complete and partial response rates and time to progression in patients with refractory advanced colorectal carcinoma treated with cetuximab and irinotecan. [ Time Frame: baseline to 40 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the safety and toxicity profile of this regimen in these patients. [ Time Frame: baseline to 40 weeks ] [ Designated as safety issue: Yes ]
  • Assess the quality of life of patients treated with this regimen. [ Time Frame: baseline to 40 weeks ] [ Designated as safety issue: No ]
  • Determine the tumor epidermal growth factor receptor levels in patients treated with this regimen [ Time Frame: baseline to 40 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: October 1999
Study Completion Date: July 2005
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EgFR antibody Biological: cetuximab Drug: irinotecan hydrochloride

Detailed Description:

OBJECTIVES: I. Determine the complete and partial response rates and time to progression in patients with refractory advanced colorectal carcinoma treated with cetuximab and irinotecan. II. Determine the safety and toxicity profile of this regimen in these patients. III. Assess the quality of life of patients treated with this regimen. IV. Determine the tumor epidermal growth factor receptor levels in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified by response to irinotecan based chemotherapy regimen (stable disease vs disease progression). Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive maintenance cetuximab IV over 1 hour on days 8, 15, 22, 29, and 36. Patients receive irinotecan IV over 90 minutes (beginning 1 hour after completion of cetuximab infusion) at the same regimen (dosage and frequency) on which the patient became refractory to irinotecan therapy. Irinotecan is administered at a higher dose on days 1 and 22 OR at a lower dose on days 1, 8, 15, and 22. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with unacceptable toxicity to irinotecan may continue on cetuximab maintenance therapy alone at the discretion of the protocol investigator and sponsor. Quality of life is assessed before initiation of study therapy, at the completion of each course, and then at 4 weeks after completion of study. Patients are followed at 4 weeks.

PROJECTED ACCRUAL: Approximately 110 patients (55 per strata) will be accrued for this study within 7 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically proven refractory advanced colorectal carcinoma Must have 1 of the following: Stable disease after receiving a minimum of 12 weeks of irinotecan Disease progression at any time after receiving an irinotecan containing regimen No prior chemotherapy for colorectal carcinoma during the interval between the irinotecan containing regimen and study entry Bidimensionally measurable disease Index lesions must be outside prior radiation ports Epidermal growth factor receptor (EGFr) expression (1+ or greater) must be confirmed prior to study entry Patients who have no tumor tissue available for immunohistochemical assay of EGFr testing undergo biopsy of accessible tumor No meningeal or CNS involvement by tumor

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN ALT and AST no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No clinically significant cardiac disease No serious arrhythmias No significant conduction abnormalities Neurologic: No uncontrolled seizure disorder No active neurologic disease No grade 2 or worse neuropathy Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 3 years except basal cell skin cancer or preinvasive carcinoma of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior murine monoclonal antibody therapy or cetuximab Chemotherapy: See Disease Characteristics Recovered from any toxicities No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 2 months since prior radiotherapy and recovered No concurrent radiotherapy Surgery: See Disease Characteristics At least 1 month since prior surgery except diagnostic biopsy Other: At least 1 month since prior investigational agents

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005076

Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Study Chair: Albert F. LoBuglio, MD University of Alabama at Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00005076     History of Changes
Other Study ID Numbers: CDR0000067683, UAB-9926, IMCL-CP02-9923, MSKCC-99089, UAB-F990927004, UCLA-9908082, NCI-G00-1723
Study First Received: April 6, 2000
Last Updated: April 10, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Alabama at Birmingham:
stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Cetuximab
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014