Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation
Conditions
Brief summary
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
Interventions
DRUGAfatinib
Open label
DRUGPaclitaxel
Paclitaxel
Sponsors
AZ-VUB
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women and men with locally advanced or metastatic cancers harboring either an activating EGFR mutation or a HER2 mutation or a HER3 mutation * Failure of at least one line of standard systemic therapy * No eligibility for other open genomic driven phase I, II or III trial available for these tumor genotypes * ECOG performance status ≤2 * Patient with a life expectancy \>3 months * Patients able to provide written informed consent prior to enrollment into the clinical trial. * Adequate organ function
Exclusion criteria
* Non squamous non-small cell lung cancer harbouring an EGFR mutation (registered indication) * Chemotherapy, biological therapy or investigational agents within four weeks prior to the start of study treatment * Known hypersensitivity to afatinib or the excipients of any of the trial drugs * Prior treatment with afatinib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response rate | 6 weeks |
| Incidence and intensity of adverse events | 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate | 6 weeks |
| Progression free survival | 6 weeks |
| Overall survival | 6 weeks |
Countries
Belgium
Contacts
Primary ContactLore Decoster, Dr
Backup ContactNadia Cappoen
Outcome results
None listed