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

NCT00083720 | Completed Phase 2 Results

• 1 other identifier: CP02-0451
• Study Type: interventional
• Target: 87
• Locations: 2 countries
• Sites: 27

Brief Summary

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.

Conditions

Colorectal Neoplasms; Metastases; Neoplasm

Keywords

EGFR-undetectable; Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Percentage of Participants With Disease Control (CR, PR, or SD)

  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

  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

  Patients with PD after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine (range: 1-3 months).

• Overall Survival

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

Study Arms (1)

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

Interventions

cetuximab BIOLOGICAL

Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes

Also known as: Erbitux™

cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Bristol-Myers Squibb: collaborator

Study Sites (27)

ImClone Investigational Site

Campbell, California, 95008, United States

Location

ImClone Investigational Site

Los Angeles, California, 90033, United States

Location

ImClone Investigational Site

Soquel, California, 95073, United States

Location

ImClone Investigational Site

Jacksonville, Florida, 32256, United States

Location

ImClone Investigational Site

Orlando, Florida, 32804, United States

Location

ImClone Investigational Site

Ormond Beach, Florida, 32174, United States

Location

ImClone Investigational Site

Gurnee, Illinois, 60031, United States

Location

ImClone Investigational Site

Evansville, Indiana, 47714, United States

Location

ImClone Investigational Site

Indianapolis, Indiana, 46202, United States

Location

ImClone Investigational Site

Lexington, Kentucky, 40503, United States

Location

ImClone Investigational Site

Louisville, Kentucky, 40202, United States

Location

ImClone Investigational Site

Metairie, Louisiana, 70006, United States

Location

ImClone Investigational Site

Boston, Massachusetts, 02114, United States

Location

ImClone Investigational Site

Ann Arbor, Michigan, 48106-0995, United States

Location

ImClone Investigational Site

Kalamazoo, Michigan, 49048, United States

Location

ImClone Investigational Site

St Louis, Missouri, 63110, United States

Location

ImClone Investigational Site

Armonk, New York, 10504, United States

Location

ImClone Investigational Site

East Setauket, New York, 11733, United States

Location

ImClone Investigational Site

Durham, North Carolina, 27710, United States

Location

ImClone Investigational Site

Sellingsgrove, Pennsylvania, 17870, United States

Location

ImClone Investigational Site

Arlington, Texas, 76012, United States

Location

ImClone Investigational Site

Bryan, Texas, 77802, United States

Location

ImClone Investigational Site

Temple, Texas, 76508, United States

Location

ImClone Investigational Site

Oshawa, Ontario, L1G 2B9, Canada

Location

ImClone Investigational Site

Ottawa, Ontario, K1H 1C4, Canada

Location

ImClone Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

ImClone Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: ImClone, LLC

ClinicalTrials@imclone.com

Study Officials

• E-mail: ClinicalTrials@ ImClone.com

  Eli Lilly and Company

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 28, 2004
• First Posted: June 2, 2004
• Study Start: October 1, 2004
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: May 25, 2011
• Results First Posted: October 23, 2009

Record last verified: 2011-05

Locations

US (23); CA (4)