Trial Name
New EPOC Trial - An open-label randomised trial, comparing OxMdG / IrMdG chemotherapy versus OxMdG / IrMdG chemotherapy plus Cetuximab.
Description
A prospective randomised open label trial of oxaliplatin/irinotecan plus fluorouracil versus oxaliplatin/irinotecan plus fluorouracil and cetuximab pre and post operatively in patients with resectable colorectal liver metastasis requiring chemotherapy.
Objectives
Primary Objective:
•To determine whether the addition of Cetuximab to Oxaliplatin plus modified de Gramont or Irinotecan plus modified de Gramont combination chemotherapy results in improved progression free survival when compared with combination chemotherapy alone in patients who do not possess a kRAS mutant genotype confirmed by laboratory analysis.
Secondary Objectives:
•To evaluate overall survival.
•To evaluate quality of life.
•To compare the experimental arm in terms of cost effectiveness in a UK treatment setting.
•To determine whether the addition of Cetuximab to combination chemotherapy as above results in improved progression free survival when compared with combination chemotherapy alone in patients who possess the kRAS-wt genotype confirmed by laboratory analysis.
Translational Research Objectives:
•To assess the difference in progression free survival with chemotherapy plus Cetuximab for all patients irrespective of EGFR detectability in tumour tissue on IHC; for patients with detectable EGFR and for those with undetectable EGFR.
•To determine, from DNA extracted from peripheral blood, the impact of individual variance in DNA repair capacity on tumour response, progression free survival and grade 3/4 toxicities.
•To determine, from DNA extracted from peripheral blood, whether variance in the enzymes involved in the metabolism, transport and cellular targets of the drugs used affects tumour response, progression free survival and grade 3/4 toxicities.
•To determine the effect of Cetuximab on the expression profile of hepatic metastases.
Design
Patients will be randomised at the start of chemotherapy to receive either:
Arm A: OxMdG / IrMdG chemotherapy
Arm B: OxMdG / IrMdG chemotherapy with Cetuximab
OxMdG: l-folinic acid (175 mg flat dose IV over 2 h) or d,l-folinic acid (350 mg flat dose IV over 2 h), concurrent administration of Oxaliplatin (85 mg/m2 IV over 2 h) plus 5 minute bolus of 5FU (400 mg/m2) followed by a 46 h IV infusion of 5FU 2400 mg/m2 repeated every 2 weeks as used in the FOCUS trial.
IrMdG: Irinotecan 180 mg/m2 IV over 30 minutes, l-folinic acid (175 mg flat dose IV over 2 h) or d,l-folinic acid (350 mg flat dose IV over 2 h) plus 5 minute bolus of 5FU (400 mg/m2) followed by a 46 h IV infusion of 5FU 2400 mg/m2 repeated every 2 weeks as used in the FOCUS trial in patients intolerant of Oxaliplatin.
Cetuximab will be given as a fortnightly dose of 500 mg/m2 with OxMdG and IrMdG. Patients will receive 12 weeks of chemotherapy, undergo surgery and then complete a further 12 weeks of chemotherapy.
Patients will receive 12 weeks of pre-operative and 12 weeks of post-operative chemotherapy dependent on cumulative toxicity, post-surgical performance status or because of patient choice to stop chemotherapy. Follow-up visits will be arranged every 3 months for 2 years and every 6 months for a further 3 years thereafter until disease progression and/or death.
Status
Completed
Population
288 colorectal cancer patients with liver metastases deemed resectable in whom the oncologist feels chemotherapy would be beneficial and who are fit for combination chemotherapy.
Publications
New EPOC study protocol, v14 11-Oct-2017
Contact Details
All Trial enquiries should be addressed to [email protected]
This trial was funded by Cancer Research UK (award reference no. C317/A7275)