This is a phase II, multicenter, open-label study of cetuximab in patients with epidermal growth factor receptor (EGFR) negative, metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine. Target enrollment is 80 evaluable patients. Patients with EGFR-negative metastatic colorectal carcinoma who have progressed after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine, will receive an initial dose of cetuximab, 400 mg/m2 , intravenously (i.v.) over 120 minutes, followed by weekly treatment with cetuximab, 250 mg/m2 i.v. over 60 minutes. Patients who experience unacceptable toxicity or who have progressive disease (PD) will not receive further cetuximab therapy. Patients will be evaluated for a tumor response at a minimum of every 6 weeks while on cetuximab therapy. Patients with stable disease (SD), partial response (PR), or a complete response (CR) may continue to receive weekly cetuximab therapy, unless they are dose-delayed or discontinued because of toxicity. Patients who have a PR or CR must have a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response. To evaluate the objective response rate, a single-stage design will be used in this study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
ImClone Investigational Site
Campbell, California, United States
ImClone Investigational Site
Los Angeles, California, United States
ImClone Investigational Site
Soquel, California, United States
ImClone Investigational Site
Jacksonville, Florida, United States
ImClone Investigational Site
Orlando, Florida, United States
ImClone Investigational Site
Ormond Beach, Florida, United States
ImClone Investigational Site
Gurnee, Illinois, United States
ImClone Investigational Site
Evansville, Indiana, United States
ImClone Investigational Site
Indianapolis, Indiana, United States
ImClone Investigational Site
Lexington, Kentucky, United States
...and 17 more locations
Percentage of Participants With an Overall Resonse
Determine the response rate (complete response \[CR\] and partial response \[PR\]) in patients with epidermal growth factor receptor (EGFR)-negative metastatic colorectal carcinoma treated with cetuximab, as classified by the investigator according to the World Health Organization (WHO) criteria. The calculation was the total number of patients with CR or PR divided by the total number of patients treated.
Time frame: Tumor evaluations were performed at a minimum every 6 weeks while on cetuximab therapy until progressive disease (PD) or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.
Number of Participants With Adverse Events
Reported adverse events (AEs) per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities dictionary. The National Cancer Insititute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 was used to grade all AEs. The collection of AEs began at the time the patient received the first cetuximab dose and continued during the study until 30 days after the last dose of cetuximab. All patients who were enrolled and treated with cetuximab were assessed for safety (mITT population, as treated).
Time frame: An adverse event (AE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.
Number of Participants With Serious Adverse Events
Reported SAEs per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities. The NCI-CTCAE Version 3.0 was used to grade all SAEs. An SAE was any untoward medical occurrence that resulted in death, persistent/significant disability/incapacity, was life threatening, required inpatient hospitalization or caused prolongation of existing hospitalization,congenital anomaly/birth defect, or any important medical event.
Time frame: A serious adverse event (SAE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.
Percentage of Participants With Disease Control (CR, PR, or SD)
This is the total number of patients with a best overall response of CR, PR, and stable disease (SD) divided by the total number of patients treated.
Time frame: Tumor evaluations were performed at a minimum of every 6 weeks while on cetuximab therapy. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response.
Duration of Response
In patients with a best overall response of CR or PR, the duration of response is measured from the date criteria are first met for CR or PR, until the first date that Progressive Disease (PD) is objectively documented or death occurs. Duration of response of living patients with no evidence of PD was censored on the date of their last tumor assessment.
Time frame: The duration of response was measured from the date of response to the first date of PD (range 2 to 7 months).
Time to Progression
This measure was defined as the time from the first day of treatment until the date of PD. Deaths without objective progression were censored. Patients who did not progress were censored at their last day of tumor assessment.
Time frame: Patients with PD after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine (range: 1-3 months).
Overall Survival
This measure is defined as the time from the first day of therapy to the date of death. Survival of living patients or those lost to follow-up were censored on the last date the patients were known to be alive.
Time frame: Survival information was collected every 3 months after completion of therapy and/or follow-up up to 24 months.
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