Trial Information

A Two-arm Phase II Randomised Trial of Intermittent Chemotherapy Plus Continuous Cetuximab and of Intermittent Chemotherapy Plus Intermittent Cetuximab in First Line Treatment of Patients With K-ras-normal (Wild-type) Metastatic Colorectal Cancer

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.