EGFR-mutation, HER2-expression, NSCLC
Conditions
Keywords
NSCLC, HER2-expression, EGFR-mutation, Trastuzumab, Paclitaxel
Brief summary
This study is a pilot study in EGFR-mutated NSCLC patients who have progressed on standard-dose TKIs. Tumor biopsies will be evaluated for HER2-expression. In case of HER2 expression, patients can participate in the trial after obtaining informed consent. Patients will be treated with weekly paclitaxel-trastuzumab.
Interventions
DRUGPaclitaxel-trastzumab
Trastuzumab * Dose: * First dose: 4 mg/kg IV * Subsequent doses: 2 mg/kg every week IV. * The patient must be monitored for at least 6 hours after the start of the first infusion and for at least 2 hours after the start of subsequent infusions. Paclitaxel \- Dose: 60 mg/m2 IV in 30 minutes, every week, after trastuzumab
Sponsors
Amsterdam UMC, location VUmc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed stage IV non-squamous NSCLC patients. * Patients must have been detected with an activating EGFR mutation at baseline and must have yet progressed on erlotinib, gefitinib or afatinib monotherapy in daily dose of 150 mg, 250 mg or 40 mg respectively. (Patients with unknown mutation status that have exhibited a response to these agents or stable disease for at least 6 months while on treatment with gefitinib or erlotinib are also eligible). * Rebiopsy after having acquired resistance to TKI-treatment must have been performed and HER2-overexpression (positive immunohistochemistry staining) must have been detected. * There must be at least one measurable disease site, according to RECIST 1.1 criteria. * WHO performance status 0-2. * Willing and able to comply with the study prescriptions. * 18 years or older. * Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study. * Ability to give written informed consent before patient registration.
Exclusion criteria
* No uncontrolled infectious disease. * No other active malignancy. * No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy or VATS biopsy) in the previous 4 weeks. * No treatment with investigational drugs. * No known hypersensitivity to trastuzumab-paclitaxel * No symptomatic brain metastases. * History of coronary artery disease, NYHA class III or IV and Left Ventricular Ejection Fraction (LVEF) of \<45%.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate | 6 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate | 6 weeks |
| progression-free survival | 2 years |
| Toxicity | 2 years |
Countries
Netherlands
Contacts
Primary ContactJustine Kuiper, MD
Outcome results
None listed