Phase II Study of Anti-Epidermal Growth Factor Receptor (EGFr) Antibody Cetuximab in Combination With Chemotherapy in Patients With Advanced Colorectal Carcinoma
18 Years
N/A
Both
Colorectal Cancer
Trial Information
Phase II Study of Anti-Epidermal Growth Factor Receptor (EGFr) Antibody Cetuximab in Combination With Chemotherapy in Patients With Advanced Colorectal Carcinoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the complete and partial response rates and time to progression in patients with refractory advanced colorectal carcinoma treated with cetuximab and irinotecan.
Outcome Time Frame:
baseline to 40 weeks
Safety Issue:
No
Principal Investigator
Albert F. LoBuglio, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Alabama at Birmingham
Authority:
United States: Federal Government
Study ID:
CDR0000067683
NCT ID:
NCT00005076
Start Date:
October 1999
Completion Date:
July 2005
Related Keywords:
- Colorectal Cancer
- stage III colon cancer
- stage IV colon cancer
- stage III rectal cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|
