Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer

• Failure-free survival at 10 months [ Designated as safety issue: No ]
  

• Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions [ Designated as safety issue: Yes ]
  
• Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Progression-free survival [ Designated as safety issue: No ]
  
• Response rates at 12, 24, and 36 weeks [ Designated as safety issue: No ]
  
• Toxicity of each treatment regimen by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• To compare the activity, in terms of failure-free survival, of patients with K-ras-normal (wild type) advanced and/or metastatic colorectal cancer treated with intermittent combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) and intermittent vs continuous cetuximab as first-line therapy.
• To compare the safety and feasibility of these regimens in these patients.

Secondary

• To compare the safety of cetuximab reintroduction, in terms of frequency of grade 3-4 allergic reactions in these patients.
• To compare improvement in disease control (i.e., complete response plus partial response plus stable disease) at 24 weeks in patients treated with these regimens.
• To compare overall and progression-free survival of patients treated with these regimens.
• To compare response rates at 12, 24, and 36 weeks in patients treated with these regimens.
• To compare toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are randomised to 1 of 2 treatment arms.

• Arm I (intermittent chemotherapy and intermittent cetuximab): Patients receive 1 of the following combination chemotherapy and cetuximab regimens:

  • OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment repeats every 14 days for up to 6 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
  • XELOX (for patients with line-related problems): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 (28 doses). Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of 12 weeks of study therapy, patients with disease progression are removed from study. Patients with stable or responding disease stop treatment with OxMdG or XELOX and cetuximab and undergo clinical evaluation at least every 6 weeks until disease progression or clinical deterioration. Upon evidence of disease progression or clinical deterioration, patients restart treatment with OxMdG or XELOX and cetuximab as before and continue to alternate 12 weeks of treatment with treatment breaks in the absence of disease progression or unacceptable toxicity. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy or best supportive care.

• Arm II (intermittent chemotherapy and continuous cetuximab): Patients receive OxMdG or XELOX and cetuximab for 12 weeks as in arm I. Patients with disease progression after 12 weeks of study therapy are removed from study. Patients with stable or responding disease* after 12 weeks of study therapy stop treatment with OxMdG or XELOX and continue treatment with cetuximab weekly as monotherapy in the absence of disease progression or unacceptable toxicity. Patients undergo clinical evaluation as in arm I. Upon progression, patients restart treatment with OxMdG or XELOX and continue cetuximab, as before, alternating 12 weeks of combined OxMdG or XELOX and cetuximab therapy with cetuximab monotherapy. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy as in arm I.

Previously collected tumor tissue samples are obtained at baseline and analyzed by IHC for EGFR status of tumor.

After completion of study treatment, patients are followed every 12 weeks.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.