the primary objective is to characterise the impact of gefitinib on the Response Evaluation Criteria in Solid Tumours (RECIST) based assessments; objective response rate (ORR ; confirmed complete response(CR) or partial response (PR)) and disease control rate (DCR; confirmed complete response(CR) or partial response (PR) or stable disease (SD)) in patients with EGFR M+ NSCLC

A phase II Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA�) as 3rd line treatment re-challenge in Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) and who responded to gefitinib in 1st line and progressed after 2nd line chemotherapy

Inclusion Criteria at screening (Visit 1) and at Start of Study Treatment (Visit 2):

• Provision of informed consent prior to any study specific procedures.

• Histologically or cytologically confirmed NSCLC with an activating sensitising EGFR TK mutation as it was determined before starting the first gefitinib treatment by using a well-validated and robust methodology: adenocarcinoma, including Bronchoalveolar Carcinoma (BAC), squamous cell carcinoma, large cell carcinoma, adenosquamous carcinoma or undifferentiated carcinoma or not-otherwise specified NSCLC.

  • Female or male patients aged 18 years or over with Locally advanced or metastatic stage IIIB/IV disease, not suitable for therapy of curative intent or stage IV (metastatic) disease, eligible for gefitinib re-challenge treatment for NSCLC who have already received gefitinib with a documented complete (CR) or partial response (PR) or stable disease (SD) >12 weeks as the best response to their 1st gefitinib treatment and progressing during or after a subsequent anti-cancer therapy (excluding EGFR-TKIs) treatment, including but not limited to doublet platinum based chemotherapy or docetaxel monotherapy or pemetrexed monotherapy.
  • Measurable disease defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with spiral CT or MRI and which is suitable for accurate repeated measurements.
  • WHO / ECOG / Zubrod performance status 0-2.

Exclusion Criteria:

• Known severe hypersensitivity to gefitinib or any of the excipients of the product
• Prior EGFR TKIs except gefitinib followed by subsequent anti-cancer treatment (including chemotherapy and excluding EGFR-TKIs).

Previous adjuvant chemotherapy is allowed. Prior surgery or radiotherapy must be completed more than 6 months before start of study treatment. Palliative radiotherapy must be completed at least 4 weeks before start of study treatment with no persistent radiation toxicity.

• Progression disease or stable disease (SD) <12 weeks as best response to the 1st line treatment with gefitinib
• Not progressing during or after the last anti-cancer treatment.
• Considered to require radiotherapy to the lung at the time of study entry or in the near future
• Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease
• Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline
• Insufficient lung function as determined by either clinical examination or an arterial oxygen tension (PaO2) of < 70 Torr
• Known or suspected brain metastases or spinal cord compression, unless treated with surgery and/or radiation and stable without steroid treatment for at least 4 weeks prior to the first dose of study medication
• Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy
• Concomitant use of known CYP 3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort
• Pregnancy or breast-feeding
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (eg, unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• Life expectancy of less than 12 weeks