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

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AZ-VUB
• Collaborator: Hoffmann-La Roche
• Treatments: Erlotinib Hydrochloride

Criteria

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.