Study With Gefitinib in Combination With Olaparib (AZD2281) Versus Gefitinib Alone

Exclusion Criteria

• •1. Patients diagnosed of another neoplasm, with the exception of cervical carcinoma insitu, treated squamous cell carcinoma or superficial bladder tumor (Ta and TIS), or other malignant tumors that have received curative treatment within the last 5 years before inclusion in the study.
• •2. Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment.
• •3. Patients with HIV infection, HCV infection, coronary disease or uncontrolled arrhythmia, uncontrolled cerebrovascular disease and other clinical conditions that, in the judgment of the investigator, contraindicate the patient's participation in the study.
• •4. Past medical history of interstitial lung disease (ILD), drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease.
• •5. Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline.
• •6. Uncontrolled seizures.
• •7. Patients considered requiring radiotherapy to the lung at the time of study entry or in the near future.
• •8. 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.
• •9. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• •10. Patients who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test performed within 7 days before the onset of treatment(Appendix 8).
• •11. Patients receiving the following classes of inhibitors of CYP3A4 (see Appendix 5 for guidelines and wash out periods):
• •* Azole antifungals
• •* Macrolide antibiotics
• •* Protease inhibitors
• •12. Concomitant use of known CYP3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort.
• •13. Major surgery within 2 weeks of starting study treatment; patients must have recovered from any effects of any major surgery.
• •14. Significant weight loss (= 10% of body weight) in the 6 weeks before inclusion in the study.
• •15. Any condition that is unstable or could endanger the patient's safety and/or the patient's compliance with the study.
• •16. Substance abuse or clinical, psychological or social conditions that can undermine the validity of the informed consent or protocol compliance.
• •17. Patients who present any contraindication or suspected allergy to the products under investigation in the study. Tablets of gefitinib contain lactose: patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose and galactose malabsorption, will not be included in this trial.
• •18. Contraindication for steroid use.
• •19. Impossibility to comply with treatment due to cultural or geographic circumstances.