Trial Information

A Phase I/ II, Non-randomized, Feasibility/ Safety and Efficacy Study of the Combination of Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer

This phase I/II non randomized single center study will be performed as a two step design.
Part I is dose finding, whereby dose escalations will be performed for everolimus and
capecitabine. Part II is the efficacy study. At the MTD doses in part II biomarker studies
will be performed in blood and tumor tissue. Study design phase I part: The first week
patients will be treated with everolimus alone. Capecitabine will be administered for 14
days in a 3 weekly cycle, starting on day 8. Cetuximab will be administered weekly, starting
at day 8. The dose is fixed for cetuximab during study treatment, whereas the doses of
everolimus and capecitabine will differ per dose level. First dose level: Everolimus 5 mg
daily continuously, Capecitabine 600 mg/m2 bid for 2 weeks every 3 weeks, Cetuximab 400mg/m2
(120 min infusion) first dose, thereafter 250 mg/m2 (60 min infusion) weekly. Second dose
level: Everolimus 10 mg daily continuously, Capecitabine 600 mg/m2 bid for 2 weeks every 3
weeks, Cetuximab 400mg/m2 (120 min infusion) first dose, thereafter 250 mg/m2 (60 min
infusion) weekly. Third dose level: Everolimus 10 mg daily continuously, Capecitabine 800
mg/m2 bid for 2 weeks every 3 weeks, Cetuximab 400mg/m2 (120 min infusion) first dose,
thereafter 250 mg/m2 (60 min infusion) weekly. Study design phase II part At the MTD 14-25
patients with pancreatic cancer will be included. In the phase II part, everolimus will be
administered during one week before start of cetuximab. At day 8 the first dose of cetuximab
will be administered. Capecitabine will be started one week thereafter. This enables us to
perform pharmacodynamic studies to assess biomarker changes during the different phases of
treatment. Everolimus will be administered continuously in a dose of 5 or 10 mg orally once
daily (dependent on MTD from part 1). Capecitabine will be administered orally in a dose of
400 - 800 mg/m2 twice daily for 14 days followed by one week rest (dependent on MTD from
part 1). Patients will receive cetuximab infusions via an infusion pump, with an initial
dose of 400 mg/m² (over 120 min) and subsequent weekly infusions of 250 mg/m² (over 60 min),
starting day 8.