Protocol

CEEOG 0106/ML20033

Study title

An open label phase II study evaluating the effectiveness of first line EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer patients selected by positive FISH EGFR test (FLIKER)

Study start date

December 12, 2007

Study status

Open

Study design

A multicenter, open-label, single-arm phase II clinical trial. NSCLC patients who are chemo-naive are registered for screening (EGFR gene copy number by FISH). Upon positive test, patients are included in the study and treated with erlotinib until disease progression, unacceptable toxicity or withdrawn consent. Continuous oral erlotinib is given once daily at a dose of 150 mg. Dose reductions are permitted and based on tolerability to drug therapy. Patients with negative test are offered the best available treatment (most often chemotherapy or palliative radiotherapy) or best supportive care according to the decision of their primary physician.

Sample size

72 patients

Study objectives

The primary objective of this study:

The primary objective of the trial is to determine the efficacy (as measured by the proportion of patients alive and free of progression at 12 months after study entry) of EGFR TKI inhibitor erlotinib in first line treatment of advanced NSCLC patients selected by positive FISH EGFR.

The secondary objective of this study:

To assess the response rate, overall survival, and clinical benefit proportion.

To perform exploratory molecular studies of other markers predicting response and survival benefit from erlotinib.

Patient population

Patients must meet all of the following inclusion criteria to be eligible for participation in this program.

Inclusion Criteria:

• histologically confirmed NSCLC

• stage IIIB with pleural effusion or stage IV at study entry

• paraffin-embedded tumor sample available for sensitivity analysis (microscopic diagnosis only by cytology renders the patient ineligible for this trial

• measurable tumor according to RECIST criteria

• Age > 18 years

• WHO Performance Status 0 - 2

• Adequate liver and renal function (ALT < 2,5 UNL or ALT < 5 ULN in patients with liver metastases, bilirubin within normal limits, creatinine < 1.5 ULN) and adequate haematology (haemoglobin >11 g/dL, WBC>2.000/µL, PLT>100.000/µL)

• Patients of reproductive potential must use adequate contraception

• No previous systemic anticancer treatment. Previous radiotherapy is allowed provided marker lesions are outside the irradiated volume

• No histological diagnosis of SCLC or mixed NSCLC/SCLC type

• Stable medical conditions (e.g. no psychotic disorders, drug abuse, active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within 12 months, hepatic or renal insufficiency)

• No history of malignancy diagnosed within last 5 years prior to enrollment other than basal-cell skin cancer or in situ cervical cancer

• No participation in any investigational study within 30 days prior to enrollment

• No pregnancy or lactation

• No known hypersensitivity to erlotinib or to any of the excipients

• Written informed consent

• Positive EGFR FISH test defined as: high level of polysomy (≥4 copies of the gene in ≥40% of cells) or gene amplification, defined by presence of tight gene clusters and a ratio gene/chromosome per cell ≥2, or ≥15 copies of the genes per cell in ≥10% of analyzed cells.

Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be undimensionally measurable as follows: Spiral CT scan > 10 mm, Non-spiral CT scan > 20 mm.

List of Sites participating in the study

No	Center and addresss	Date of Site Initiation Visit
1	Dr Ewa Szutowicz- Zielińska Klinika Onkologii I Radioterapii ul. Debinki 7 80-211 Gdańsk	12/12/2007
2	Dr Sergiusz Nawrocki Zakład Radioterapii ZOZ MSW Warmińsko- Mazurskie Centrum Onkologii ul. Wojska Polskiego 37 10-228 Olsztyn	30/01/2008
3	Dr Marcin Murmyło Dolnośląskie Centrum Chorób Płuc ul. Grabiszyńska 105 53-439 Wrocław	20/11/2008
4	Dr Kazimierz Drosik Oddział Onkologii KlinicznejOpolskie Centrum Onkologiiul. Katowicka 66a45-060 Opole	15/01/2008
5	Dr Aleksandra Szczęsna Oddział III Chorób Płucul .Reymonta 83/9105-400 Otwock	09/05/2008
6	Prof. Cezary Szczylik Klinika Onkologiiul Szaserów 12804-141 Warszawa	24/02/2009
7	Dr Andrzej Każarnowicz Oddział V Chemioterapii Nowotworów Płuc Samodzielny Publiczny Zespół Gruźlicy i Chorób Płucul. Jagielońska 7810-357 Olsztyn	08/09/2009

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