Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation Clinical Trial
Official title:
An Open Explorative Phase II, Open Label Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation
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
n/a