Hoog-gedoseerde, pulsatiele erlotinib na progressie op standaard dosering erlotinib bij EGFR-gemuteerde NSCLC patienten.

Rationale:

High-dose, weekly erlotinib is a therapeutic option for EGFR-mutated NSCLC patients with leptomeningeal metastases while on EGFR-TKI therapy. In one of the patients treated with this dose schedule not only the leptomeningeal metastases showed evident response, but unexpectedly, the thoracic progression of disease showed evident response as well. This provides the rationale for this prospective trial; does erlotinib in a high-dose, weekly schedule show activity in EGFR-mutated NSCLC patients after being diagnosed with progression of disease while on standard dose EGFR-TKI therapy.



Objective:

To evaluate the effect of erlotinib 1500 mg weekly in EGFR-mutated NSCLC patients after being diagnosed with disease progression while on standard, daily dose of 150 mg erlotinib.



Study design:

Single-arm, open-label, phase II, intervention study.



Study population:

EGFR-mutated NSCLC patients, >18 years old.



Intervention:

Erlotinib 1500 mg once weekly.



Main study parameters/endpoints:

Primary objective: Disease control rate at 8 weeks.
Secondary objective: progression free survival at 6 months, overall survival at 1 year and toxicity according to CTC-AE 4.0.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Burden and risks associated with participation include outpatient visits every 4 weeks and a CT-scan every 8 weeks. Risks comprise the side effects of erlotinib, which are generally well manageable with best supportive care. Every outpatient visit physical examination will be performed, blood samples will be taken and every 8 weeks a CT-scan will be done. Risks are considered to be small, since there is much experience with erlotinib in this dose and schedule and side effects have been manageable.

High-dose, weekly erlotinib is a therapeutic option for EGFR-mutated NSCLC patients with leptomeningeal metastases while on EGFR-TKI therapy. In one of the patients treated with this dose schedule not only the leptomeningeal metastases showed evident response, but unexpectedly, the thoracic progression of disease showed evident response as well. This provides the rationale for this prospective trial; does erlotinib in a high-dose, weekly schedule show activity in EGFR-mutated NSCLC patients after being diagnosed with progression of disease while on standard dose EGFR-TKI therapy.

Every 8 weeks CT thorax.

Erlotinib 1500 mg once a week. This will be given until progression of disease.