Phase II single arm study of afatinib in combination with cetuximab in EGFR exon 20 insertion positive non-small-cell lung cancer
- Conditions
- lung cancernon-small cell lung cancer10038666
- Registration Number
- NL-OMON55757
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 37
• Pathologically or cytologically confirmed stage IV NSCLC, harboring an EGFR
exon 20 insertion mutation.
• 18 years or older at time of study entry.
• Life expectancy of at least three months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see
Appendix 1).
• Measurable disease, according to RECIST 1.1.
• At baseline adequate fresh or archived tissue from a histological biopsy or a
cellblock obtained by fine needle aspiration of a tumor lesion that is not
radiated prior to biopsy, must be available. Baseline tissue samples must have
been obtained after the last line of systemic therapy prior to study entry.
• Adequate normal organ and marrow function as defined below:
• Absolute leukocyte count >= 3 x 109/L (> 3000 per mm3)
• Platelet count >= 75 x 109/L (>75,000 per mm3)
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) <= 3 x
institutional upper limit of normal unless liver metastases are present, in
which case it must be <= 5x ULN.
• Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula or by 24-hour
urine collection for determination of creatinine clearance.
• Women of child-bearing potential: these subjects must have a negative serum
pregnancy test within 7 days prior to the first dose of study treatment and
agree to use highly effective contraception, as defined in section 5.2.2, from
7 days prior to enrollment, throughout the treatment period and for seven
months after completion of the treatment with cetuximab.
• Males must agree to take appropriate precautions to avoid fathering a child
from the first dose of study treatment through 3 months after the final
administration of investigational drugs.
• Subject is willing and able to comply with the protocol for the duration of
the study including undergoing treatment and scheduled visits and examinations
including follow up.
• Ability to give written informed consent before patient registration.
• Participation in another clinical study with an investigational product
during the last 2 weeks.
• Prior treatment with EGFR targeting antibodies (prior treatment with EGFR
TKI*s is allowed).
• Other active malignancy.
• History of hypersensitivity to afatinib or cetuximab.
• Major surgery (excluding diagnostic procedures e.g. mediastinoscopy or VATS
biopsy) within 28 days of the start of study treatment.
• Radiotherapy less than two weeks prior to the start of study treatment.
• Symptomatic brain metastases.
• Breast feeding.
• Uncontrolled intercurrent illness including ongoing or active infection,
symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis,
myocardial infarction within 12 months prior to the study entry, or psychiatric
illness/social situations that would limit compliance with study requirements
or compromise the ability of the subject to give written informed consent.
• Any other concomitant serious illness or organ system dysfunction which in
the opinion of the investigator would either compromise patient safety or
interfere with the evaluation of the safety and anti-tumor activity of the test
drugs.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Disease control rate after three cycles of a 6-week treatment course (i.e. 18<br /><br>weeks)</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Objective tumor response (CR and PR), determined by RECIST v1.1.<br /><br>• Duration of response, determined by RECIST v1.1.<br /><br>• Progression-free survival, defined as the interval between initiation of<br /><br>study treatment and the date of radiological progression, determined by RECIST<br /><br>v1.1 or death.<br /><br>• Overall survival, defined as the interval between initiation of study<br /><br>treatment and the date of death.<br /><br>• Safety as indicated by intensity and incidence of adverse events, graded<br /><br>according to NCI CTCAE Version 4.03. </p><br>