An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation

Overview

Objective(s):To investigate the efficacy and safety of afatinib in EGFR, HER 2 and HER3 mutated cancers, regardless of cancer type, excluding EGFR mutated non-small cell lung cancer. Methodology:Open label, genomic driven trial (basket trial) No. of patients total entered:Optimal Simon two stage design for the three genetic driven cohorts: 10 patients will be enrolled per cancer type in the first stage and an additional 19 in the second stage (maximum total 87 patients) Indication : cancers harbouring an EGFR mutation(excluding non-squamous non- small cell lung cancer, a registered indication), a HER2 mutation or a HER3 mutation Test product(s) : Afatinib At progression paclitaxel will be added for those patients that have no contra-indications dose: Starting dose of afatinib at 40 mg/day. Dose increase to 50 mg in the absence of adverse events. Stepwise dose reduction to 30,20, 10 mg/day according to drug-related adverse events. At progression, addition of paclitaxel 80 mg/m2 weekly 3w/4 to afatinib 40 mg/day . mode of admin. : Oral for afatinib Intravenous for paclitaxel Duration of treatment: Continuous treatment until progression or unacceptable adverse events or withdrawal of consent. At disease progression, add paclitaxel until progression or unacceptable adverse event or withdrawal of consent if no contra-indications. Criteria for efficacy: Primary Endpoint: • Response rate (CR+ PR) via RECIST v1.1 Secondary Endpoints: * Disease control rate (CR+PR+SD) * Progression free survival * Overall survival * To correlate tumor response with findings on tumor biopsies * To investigate resistance mechanisms * response rate (CR+ PR) determined by RECIST and progression free survival on the combination therapy of afatinib and paclitaxel Criteria for safety: Incidence and intensity of adverse events according CTCAE v4.0