Clinical Trial: First-Line EGFR-1 Tyrosine Kinase Inhibition in Patients With NSCLC With Mutant EGFR Gene

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Prospective Evaluation of Small Molecule EGFR-1 Tyrosine Kinase Inhibition as a First-Line Treatment in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Harbouring a Mutant EGFR Gene

Brief Summary:

Current chemotherapy for advanced non-small cell lung cancer, not amenable for curative local treatment (surgery or chemoradiotherapy), has a modest life-prolonging effect and can improve quality of life. There is however no potential for long-term cure for these patients.

Chemotherapy also produces variable and often significant toxicity. Current retrospective evidence suggests that significant clinical responses can be obtained when patients whose cancer cells have an EGFR TKD mutation are treated with an EGFR TKI.

The ease of administration and toxicity profile of TKI compare favourably with that of chemotherapy, even single agents such as for example gemcitabine The present study will establish the clinical benefit rate of TKI as a first line treatment in patients with EGFR mutations and thus estimate the proportion of patients who might benefit for a prolonged period from a treatment with a modest toxicity profile.


Detailed Summary:

Patients with stage IV NSCLC and some patients with advanced locoregional disease (stage III) are in general incurable and have a low probability for long-term survival.

Current systemic treatment in good PS patients (PS 0-1) consists of a cisplatin doublet (e.g. cisplatin plus a second drug: vinorelbine, gemcitabine, paclitaxel, docetaxel). The median and one year survival obtained with this treatment ranges between 8-10 months and 25 - 35 % respectively (1,2). Progression-free survival is a median of 5 month or less in randomized studies (3). Response rates obtained are less than 25% in metastatic disease and up to 75% in advanced locoregional disease.

Receptor tyrosine kinase inhibitors (RTKI's) are active drugs in patients with NSCLC pre-treated with cisplatin and/or docetaxel containing chemotherapy (2,4). Recently it has been shown that the EGFR1 kinase inhibitor erlotinib added to best supportive care (BSC) prolonged survival compared to BSC alone in patients with advanced NSCLC failing 1st or 2nd line chemotherapy (5).

A small number of preliminary reports have indicated that the objective response rate with these RTKI's as first line treatment in some patient populations with advanced NSCLC could be around 20 % (6), The objective (mainly partial) response in the phase II studies with pre-treated patients ranges from 10 - 15 % according to the level of pre-treatment but the control of the disease (stable disease) and improvement of symptoms without demonstrated objective response has been reported to be as high as 40 to 50 % (2,4). The addition of RTKI's or placebo to the current standard doublets (e.g. cisplatin, gemcitabine or taxol/carboplatin) has not been shown to impact on response rate, time to treatment failure or survival in large phase III randomised trial
Sponsor: AZ-VUB

Current Primary Outcome: Establish clinical benefit (progression free survival) of first line RTKI in patients with stage IV and stage IIIB NSCLC not eligible for curative-intent treatment (chemo-radiotherapy) carrying a mutant EGFR-1.

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Determine response rate (OR and stable disease) and duration under erlotinib treatment.
  • Determine the effect on Quality of Life (QOL) of first-line anti-EGFR-1 treatment.
  • Determine the value of positron emission tomography (PET)-scan as an early predictor of response and clinical benefit.
  • Overall survival from the time of study entry to the date of death or date of last follow-up.
  • Determine biological correlates for response/resistance in tumour tissues.


Original Secondary Outcome: Same as current

Information By: AZ-VUB

Dates:
Date Received: June 19, 2006
Date Started: January 2006
Date Completion:
Last Updated: June 19, 2006
Last Verified: January 2006