Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL)
Condition: Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Cetuximab; FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
Intervention description: Cetuximab intravenous infusion of 400mg/m^2 for the first infusion then weekly intravenous infusion of 250mg/m^2. Number of Cycles: until progression or unacceptable toxicity develops; Bi-weekly Irinotecan infusion of 180mg/m^2, Folinic Acid infusion of 400mg/m^2 (racemic) or 200mg/m^2 (L-form), 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-hour continuous infusion of 2400mg/m^2 Number of Cycles: until progression or unacceptable toxicity develops
Intervention MeSH terms: Leucovorin; Folic Acid; Fluorouracil; Irinotecan; Cetuximab; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1221.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic colorectal cancer; EGFR; Irinotecan; cetuximab; first-line treatment

Summary:

      Drugs used against cancer work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Monoclonal antibodies, such as
      cetuximab, can block tumor growth in different ways. Giving combination chemotherapy together
      with cetuximab as first treatment after diagnosis of a metastatic colorectal cancer
      ('1st-line' treatment) may improve the treatment efficacy. However, it is not yet known
      whether giving combination chemotherapy together with cetuximab is more effective than
      combination chemotherapy alone. This open-label trial investigates the effectiveness of
      cetuximab in combination with a standard and effective chemotherapy (5-Fluorouracil
      (5FU)/Folinic acid (FA) plus irinotecan) for metastatic colorectal cancer in first-line
      setting, compared to the same chemotherapy alone on patient expressing the epidermal growth
      factor (EGF) receptor.

      Patients expressing this EGF Receptor will be randomly assign in one of the 2 groups to
      either receive the combination chemotherapy alone or with cetuximab (open-label study) and
      will then be treated until progression of the disease or unacceptable toxicity occur. Regular
      efficacy assessments (every 8 weeks) based on imaging will be performed throughout the study
      together with regular safety assessments (e.g. safety labs). An independent Safety Board of
      experts will also monitor safety data.

      After participant discontinuation from the trial, regular updates on further treatments and
      survival status will be requested from the investigator.

      The entire study (from the first patient entering the study to the last collect of follow-up
      information) is 4-5 years long.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum

          -  Inoperable metastatic disease

          -  Immunohistochemical evidence of epidermal growth factor receptor expression in tumor
             tissue

          -  Presence of at least 1 bi-dimensionally measurable index lesion

        Exclusion Criteria:

          -  Previous irinotecan-based chemotherapy

          -  Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated
             more than 6 months before the start of study treatment

          -  Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug
             in the 30 days before the start of study treatment

          -  Brain metastasis