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Erbitux (Cetuximab) Given Alone to Patients With EGFR-Negative Metastatic Colon or Rectal Cancer That is Refractory to Chemotherapy
This study has been completed.
First Received: May 28, 2004   Last Updated: September 23, 2009   History of Changes
Sponsor: ImClone LLC
Collaborator: Bristol-Myers Squibb
Information provided by: ImClone LLC
ClinicalTrials.gov Identifier: NCT00083720
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Metastases
Neoplasm
Biological: cetuximab
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase II Multicenter Study of Erbitux (Cetuximab) in Patients With Refractory, EGFR-Negative Metastatic Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Percentage of Participants With an Overall Resonse [ 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. ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events and Serious Adverse Events [ 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of Participants With Disease Control (CR, PR, or SD) [ 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. ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: The duration of response was measured from the date of response to the first date of PD (range 2 to 7 months). ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: Patients with PD after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine (range: 1-3 months). ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Survival information was collected every 3 months after completion of therapy and/or follow-up up to 24 months. ] [ Designated as safety issue: No ]

Enrollment: 87
Study Start Date: October 2004
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
cetuximab: Experimental
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

  Eligibility

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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00083720

  Show 27 Study Locations
Sponsors and Collaborators
ImClone LLC
Bristol-Myers Squibb
Investigators
Study Director: Paul Windt, PharmD ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC ( Eric Rowinsky/ Chief Medical Officer )
Study ID Numbers: CP02-0451
Study First Received: May 28, 2004
Results First Received: April 16, 2009
Last Updated: September 23, 2009
ClinicalTrials.gov Identifier: NCT00083720     History of Changes
Health Authority: United States: Food and Drug Administration;   Canada: Ethics Review Committee;   Canada: Health Canada

Keywords provided by ImClone LLC:
EGFR-undetectable
Metastatic Colorectal Cancer

Additional relevant MeSH terms:
Digestive System Neoplasms
Antineoplastic Agents
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Neoplasm Metastasis
Gastrointestinal Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on November 05, 2009