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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00339586
Recruitment Status : Unknown
Verified January 2006 by AZ-VUB.
Recruitment status was:  Recruiting
First Posted : June 21, 2006
Last Update Posted : June 21, 2006
Hoffmann-La Roche
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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.

Condition or disease Intervention/treatment Phase
Lung Neoplasms Non-Small Cell Lung Cancer Adenocarcinoma, Bronchiolo-Alveolar Drug: Erlotinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Tyrosine

Primary Outcome Measures :
  1. 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.

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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological or cytological diagnosis of inoperable, locally advanced, recurrent or metastatic (Stage IIIB or Stage IV) adenocarcinoma of the lung in a patient with a smoking history of < 15 years and quit smoking > 1 year before diagnosis.
  • Evidence of disease but measurable disease is not mandatory.
  • 18 years of age or older.
  • ECOG performance status of 0 – 3.
  • Patients not eligible for standard curative-intent treatment with surgery or chemo-radiotherapy.
  • Life expectancy ³ 3 months.
  • Prior therapy for NSCLC allowed for primary disease: surgery and radiotherapy and adjuvant or proto-adjuvant chemotherapy completed > 6 months before inclusion
  • Adequate bone marrow, hepatic and renal function:

Granulocyte count > 1.5 x 109/L and platelet count > 100 x 109/L Serum bilirubin must be < 1.5 upper limit of normal (ULN). If alkaline phosphatase is > 2.5 x ULN, SGOT (AST) and SGPT (ALT) must be < 1.5 x ULN.

Serum creatinine < 1.5 ULN or creatinine clearance > 60 ml/min.

  • Ability for giving informed consent for participating in the study and filling out FACT-L quality of life scales.
  • Able to comply with study and follow-up procedures.
  • Availability of tumour biopsy sample (fixed in formalin and, if possible, also snap frozen tumour sample). If frozen samples are available, these will be collected by central data management.
  • Signed Informed Consent for performing mutation analysis and subsequent biomarker analysis.
  • Separate signed Informed Consent for participation in the treatment phase of the study.
  • Ability to take oral medication.
  • For all females of childbearing potential a negative pregnancy test must be obtained within 48 hours before starting therapy.

Exclusion Criteria:

  • Patients for whom urgent chemotherapy or radiotherapy is deemed necessary (e.g. rapidly progressive disease).
  • Current symptomatic central nervous disorder, brain or leptomeningeal metastasis.
  • Pre-existing symptomatic interstitial lung disease, not related to the current malignancy.
  • Patients with a history of other malignancies, except patients with basal cell carcinoma of the skin or in situ carcinoma of the cervix with a disease free interval of ³ 5 years. Patients with a prior history of other good prognosis malignancies more than 5 years since end of treatment and in un-maintained complete remission also can be considered for inclusion
  • Prior therapy with systemic anti-tumour therapy with HER1/EGFR inhibitors (small molecule or monoclonal antibody) or chemotherapy
  • Significant malabsorption syndrome or disease affecting the gastrointestinal tract function
  • Pregnant or breast-feeding women; for women in reproductive condition, a negative pregnancy test is required.
  • Concomitant food or drug intake which potentially impairs absorption and metabolisation of RTKI's.
  • Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
  • Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease).
  • Any significant ophthalmological abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00339586

Contact: Jacques De Grève, MD PhD 0032 2 477 64 15
Contact: Nicolas Fontaine, Mr 0032 2 477 54 61

AZ VUB Recruiting
Jette, Belgium, 1090
Contact: Jacques De Grève, MD PhD    0032 2 477 64 15   
Contact: Nicolas Fontaine, Mr    0032 2 477 54 61   
Principal Investigator: Jacques De Grève, MD PhD         
Sponsors and Collaborators
Hoffmann-La Roche
Principal Investigator: Jacques De Grève, MD PhD AZ-VUB

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00339586     History of Changes
Other Study ID Numbers: FIELT
VUB 05-002
First Posted: June 21, 2006    Key Record Dates
Last Update Posted: June 21, 2006
Last Verified: January 2006

Keywords provided by AZ-VUB:
Non-small cell lung cancer
tyrosine kinase inhibition
first-line treatment
mutant EGFR-gene

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma, Bronchiolo-Alveolar
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type