Erbitux (Cetuximab) Given Alone to Patients With EGFR-Negative Metastatic Colon or Rectal Cancer That is Refractory to Chemotherapy
Condition: Colorectal Neoplasms; Metastases; Neoplasm
MeSH terms: Neoplasms; Colorectal Neoplasms
Intervention: cetuximab
Intervention description: Initial dose of 400 mg/m2 intravenously (i.v.) over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: EGFR-undetectable; Metastatic Colorectal Cancer

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.
    

Eligibility 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.