Trial Information

A Three-Arm Randomised Controlled Trial Comparing Either Continuous Chemotherapy Plus Cetuximab or Intermittent Chemotherapy With Standard Continuous Palliative Combination Chemotherapy With Oxaliplatin and a Fluoropyrimidine in First Line Treatment of Metastatic Colorectal Cancer (COIN)

OBJECTIVES:

Primary

- Compare the overall survival of patients with metastatic colorectal adenocarcinoma
treated with continuous combination chemotherapy comprising oxaliplatin, leucovorin
calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) with vs
without cetuximab vs intermittent combination chemotherapy with OxMdG or XELOX as
first-line therapy.

Secondary

- Compare time of disease control and progression- and failure-free survival of patients
treated with these regimens.

- Compare response in patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Compare the cost effectiveness of these regimens in these patients.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter, open label, randomized, controlled study. Patients are
randomized to 1 of 3 treatment arms.

- Arm I (continuous chemotherapy): Patients receive 1 of the following combination
chemotherapy regimens of their choice (or as per participating center):

- OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over
2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Courses repeat
every 14 days in the absence of disease progression or unacceptable toxicity.

- XELOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine
twice daily on days 1-14. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

- Arm II (continuous chemotherapy and cetuximab): Patients receive OxMdG or XELOX as in
arm I. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8 (for patients
receiving OxMdG) OR days 1, 8, and 15 (for patients receiving XELOX). Treatment with
OxMdG and cetuximab repeats every 14 days in the absence of disease progression or
unacceptable toxicity. Treatment with XELOX and cetuximab repeats every 21 days in the
absence of disease progression or unacceptable toxicity.

- Arm III (intermittent chemotherapy): Patients receive OxMdG or XELOX as in arm I.
Treatment with OxMdG repeats every 14 days for up to 6 courses (12 weeks). Treatment
with XELOX repeats every 21 days for up to 4 courses (12 weeks). Patients with disease
progression after 12 weeks of therapy are removed from study treatment. Patients with
stable or responding disease after 12 weeks of therapy stop treatment and undergo
clinical evaluation at least every 6 weeks (treatment break) until disease progression
or clinical deterioration. Upon evidence of disease progression or clinical
deterioration, patients restart treatment with OxMdG or XELOX as before and continue to
alternate 12 weeks of treatment with treatment breaks in the absence of disease
progression or unacceptable toxicity Quality of life is assessed at baseline, 6 weeks,
12 weeks, and then every 12 weeks thereafter.

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

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 2,421 patients (807 per treatment arm) will be accrued for
this study within 3.5 years.