Trastuzumab-emtansine and osimertinib combination treatment to target HER2 bypass track resistance in EGFR mutation positive NSCLC
- Conditions
- lung cancernon-small cell lung cancer10038666
- Registration Number
- NL-OMON55787
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 58
-Histologically or cytologically confirmed stage IV non-squamous NSCLC,
characterized by an activating EGFR mutation., -Progressive disease according
to RECIST 1.1 on first, second or third generation EGFR TKI and still receiving
the drug., -A rebiopsy after having acquired resistance to a first, second or
third generation TKI-treatment must have been performed and be:, a. Negative
for T790M in case of treatment with a first or second generation EGFR TKI.
After progression on a third generation EGFR TKI patients may either be
positive or negative for T790M., b. Positive for HER2-overexpression (positive
membranous immunohistochemistry staining IHC >=2+ (on a scale of 0-3) in >=10% of
the cells) must have been detected., -There must be at least one measurable
disease site, according to RECIST 1.1 criteria., -Absence of symptomatic brain
metastases. All patients will be scanned at baseline with a brain MRI.,
-Patients must be willing and able to comply with the protocol for the duration
of study including undergoing treatment and scheduled visits and examinations.,
-World Health Organization (WHO) performance status 0-2., -Patients must have a
life expectancy >=12 weeks., -Ability to give written informed consent before
patient registration., -Patients must be >=18 years of age., -Men and women of
child bearing potential should be willing to take adequate contraceptive
measures during the study and until three months after study drug
discontinuation.
-Uncontrolled infectious disease., -Other active malignancy., -Major surgery
(excluding diagnostic procedures like e.g. mediastinoscopy or VATS biopsy) in
the previous 4 weeks., -Known hypersensitivity to T-DM1 or osimertinib (or
drugs with a similar chemical structure or class) or any excipients of these
agents., -Previous treatment with a HER2 monoclonal antibody., -Clinically
significant cardiac disease or a Left Ventricular Ejection Fraction (LVEF) of
<40%., -Inadequate bone marrow reserve or organ function, as demonstrated by
any of the following laboratory values: Haematology: haemoglobin <5.6mmol/L,
absolute neutrophil count <1.5 x 10^9/L, platelet count <100 x 10^9/L.
Biochemistry: alanine aminotransferase, aspartate aminotransferase and
bilirubin <= 3x ULN, except in the case of liver metastases where these values
must be <= 5x ULN. Creatinine clearance <50 ml/min (measured or calculated by
Cockroft and Gault equation)., -Patients with symptomatic central nervous
system metastases who are neurologically unstable., -Refractory nausea and
vomiting, chronic gastrointestinal diseases, inability to swallow osimertinib
or previous significant bowel resection that would preclude adequate resorption
of osimertinib., -Patients on anticoagulant treatment will not be excluded, but
should be monitored closely during T-DM1 treatment., -Males and females of
reproductive potential who are not using an effective method of birth control
and females who are pregnant or breastfeeding or have a positive (serum)
pregnancy test prior to study entry., -Judgment by the investigator that the
patient should not participate in the study if the patient is unlikely to
comply with study procedures, restrictions and requirements.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>-Objective response rate, ORR, (according to RECIST v1.1) after three months of<br /><br>treatment course with T-DM1 and osimertinib</p><br>
- Secondary Outcome Measures
Name Time Method <p>-Safety as indicated by intensity and incidence of adverse events, graded<br /><br>according to NCI CTC AE 4.03<br /><br>-Objective tumorresponse (CR and PR), according to RECIST v1.1<br /><br>-Duration of response, according to RECIST v1.1<br /><br>-Progression-free survival, defined as the interval between initiation of study<br /><br>treatment and the date of radiological progression, determined by RECIST 1.1 or<br /><br>death<br /><br>-Overall survival, defined as the interval between initiation of study<br /><br>treatment and the date of death</p><br>