A Two Arm Phase II Study of FOLFIRI in Combination With Standard or Escalating Dose of Cetuximab as First Line Treatment of K-Ras Wild Type Metastatic Colorectal Cancer: Everest 2
Colorectal carcinoma (CRC) is the third most common form of cancer worldwide and remains a
leading malignancy both in incidence and mortality.
In the light of existing knowledge, the investigators propose a phase II open label, two arm
study in patients presenting with K-Ras wild-type metastatic colorectal tumours in the first
line setting. The standard combination of irinotecan plus infusional 5-FU/LV (FOLFIRI) and
cetuximab will be given to all patients entering the study. As the investigators hypothesize
that increasing the dose of cetuximab might increase the intensity of skin reactions that
directly correlates with outcome, in patients experiencing no skin toxicity, the dose of
cetuximab will be escalated from 250 mg/m2 to 350 mg/m2 and then up to 500 mg/m2, in order
to better define the effect of dose escalation in the first-line setting in a K-Ras wild
type tumour population and in an attempt to increase efficacy.
Pharmacokinetic studies will be performed to document PK parameters of cetuximab in patients
from both arms in selected centers.
Translational research studies are planned for all patients. Some more in depth molecular
testing will be performed in a subset of patients from whom three serial tissue samples from
accessible metastases by biopsy are available.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
PFS rate at 9 months in the dose escalation arm
To provide a precise estimate (+/- 10%) of the progression-free survival rate at 9 months, in patients without skin toxicity at 3 weeks (according to NCI CTCAE v. 4.0), treated with FOLFIRI + escalating dose of cetuximab (arm A). It is expected that the PFS rate will be similar to that observed after standard cetuximab treatment + FOLFIRI in patients with grade 1-4 skin toxicity in a K-Ras wild type population (CRYSTAL study)
Eric Van Cutsem, MD
Belgium: Federal Agency for Medicinal Products and Health Products