Erbitux (Cetuximab) Given Alone to Patients With EGFR-Negative Metastatic Colon or Rectal Cancer That is Refractory to Chemotherapy

A Phase II Multicenter Study of Erbitux (Cetuximab) in Patients With Refractory, EGFR-Negative Metastatic Colorectal Carcinoma

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 Overview

• Status: Completed
• Conditions: Colorectal Neoplasms; Neoplasm; Metastases
• Intervention / Treatment: Biological: cetuximab

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • ImClone Investigational Site
    • Ottawa, Ontario, Canada, K1H 1C4
      • ImClone Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • ImClone Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • ImClone Investigational Site
• United States
  • California
    • Campbell, California, United States, 95008
      • ImClone Investigational Site
    • Los Angeles, California, United States, 90033
      • ImClone Investigational Site
    • Soquel, California, United States, 95073
      • ImClone Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • ImClone Investigational Site
    • Orlando, Florida, United States, 32804
      • ImClone Investigational Site
    • Ormond Beach, Florida, United States, 32174
      • ImClone Investigational Site
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • ImClone Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • ImClone Investigational Site
    • Indianapolis, Indiana, United States, 46202
      • ImClone Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • ImClone Investigational Site
    • Louisville, Kentucky, United States, 40202
      • ImClone Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • ImClone Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • ImClone Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • ImClone Investigational Site
    • Kalamazoo, Michigan, United States, 49048
      • ImClone Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • ImClone Investigational Site
  • New York
    • Armonk, New York, United States, 10504
      • ImClone Investigational Site
    • East Setauket, New York, United States, 11733
      • ImClone Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • ImClone Investigational Site
  • Pennsylvania
    • Sellingsgrove, Pennsylvania, United States, 17870
      • ImClone Investigational Site
  • Texas
    • Arlington, Texas, United States, 76012
      • ImClone Investigational Site
    • Bryan, Texas, United States, 77802
      • ImClone Investigational Site
    • Temple, Texas, United States, 76508
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provided signed written informed consent.
• Histologically- or pathologically- confirmed metastatic colorectal carcinoma;
• Documented PD after treatment with at least one standard chemotherapy regimen for metastatic colorectal carcinoma;
• The chemotherapy regimen on which the patient progressed, must have included a fluoropyrimidine;
• Bidimensionally measurable disease;
• Immunohistochemical evidence of an absence of EGFR expression, (ie, EGFR-negative). Patients who do not have tumor tissue available for EGFR testing will undergo biopsy of accessible tumor. A reference laboratory designated by ImClone will perform the EGFR assay.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at study entry;
• Adequate recovery from recent surgery, chemotherapy, and radiation therapy. At least 30 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or medical device, or prior radiation therapy;
• Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.
• Men and women, 18 years of age and older

Exclusion Criteria:

• Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to cetuximab administration.
• Sexually active fertile men not using effective birth control.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
• A serious uncontrolled medical disorder that would impair the ability of the patient to receive protocol therapy;
• A history of uncontrolled angina, arrhythmias or congestive heart failure;
• Symptomatic or uncontrolled metastases to the central nervous system. Patients receiving a glucocorticoid for central nervous system (CNS) metastases will be excluded, but those receiving anticonvulsants will be eligible.
• Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for greater than or equal to 5 years will be allowed to enter the trial;
• Inadequate hematologic function defined by an absolute neutrophil count (ANC) less than 1,500/mm3 , a platelet count less than 100,000/mm3 , or a hemoglobin level less than 9 g/dL.
• Inadequate hepatic function, defined by a total bilirubin level greater than or equal to 1.5 times the upper limit of normal (ULN) and aspartate transaminase (AST) or alanine transaminase (ALT) levels greater than or equal to 5.0 times the ULN.
• Inadequate renal function defined by a serum creatinine level greater than 1.5 times the ULN.
• Prior cetuximab or other therapy, which specifically and directly targets the EGF pathway.
• Prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy.
• Any chemotherapy not indicated in the study protocol, radiation therapy, hormonal therapy (except for physiological replacement), or any other investigational agent.
• Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness.
• Employees of the investigator or study center with direct involvement in this study or other studies under the direction of the investigator or study center, as well as family members of the employees.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cetuximab; Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes	Biological: cetuximab; Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes; Other Names: Erbitux™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Survival information was collected every 3 months after completion of therapy and/or follow-up up to 24 months.

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 28, 2004
• First Submitted That Met QC Criteria: June 1, 2004
• First Posted (Estimate): June 2, 2004

Study Record Updates

• Last Update Posted (Estimate): May 25, 2011
• Last Update Submitted That Met QC Criteria: May 19, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Cancer; EGFR-undetectable
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: CP02-0451