| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Stage IIIB, IV non-small-cell lung cancer (NSCLC) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029521 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025054 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of erlotinib (Tarceva; 150 mg) on 12-month progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) in locally advanced or metastatic stages (stage IIIB and stage IV) who have not received previous chemotherapy for their disease and who present activating mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) |
|
| E.2.2 | Secondary objectives of the trial |
| •To evaluate the investigator assessed objective response •To assess the safety profile of erlotinib •To evaluate the overall survival (OS) in the study observational period •To evaluate the percentage of correlation between EGFR testing results obtained from basal tumor biopsies, from circulating tumor cells and from plasma DNA •To evaluate the percentage and type of primary and secondary resistances and correlation to response |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Patients able and willing to give written informed consent. Consent must be obtained prior to any study-specific procedure. 2. Histologically or cytologically documented inoperable, locally advanced (stage IIIB) or metastatic (stage IV) NSCLC disease who present activating mutations (exon 19 deletions or exon 21 substitution L858R) in the tyrosine kinase domain of EGFR. 3. Measurable disease must be characterized according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 4. Male or female patients aged ≥ 18 years. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 6. Life expectancy ≥ 12 weeks. 7. Adequate hematological function: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, and Platelet count ≥ 100 x 109/L, and Hemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level). 8. Adequate liver function: Total bilirubin < 1.5 x upper limit of normal (ULN), and aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) < 2.5 x ULN in patients without liver metastases; < 5 x ULN in patients with liver metastases. 9. Adequate renal function: Serum creatinine ≤ 1.25 x ULN, Creatinine clearance ≥ 60 ml/min. 10. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications. 11. Female patients must be postmenopausal (24 months of amenorrhea), surgically sterile or they must agree to use a physical method of contraception. Male patients must be surgically sterile or agree to use a barrier method of contraception. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative pregnancy test (urine or serum) within 3 days prior to enrolment into the study. Male and female patients must use effective contraception during the study and for a period of 60 days following the last administration of erlotinib. Acceptable methods of contraception include an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms) with spermicide. 12. Patients with asymptomatic and stable cerebral metastases receiving medical treatment will be eligible for the study. Those patients may have received radiation therapy for their cerebral metastases before the initiation of systemic treatment for non-small-cell lung cancer also will be eligible. |
|
| E.4 | Principal exclusion criteria |
| 1. Previous treatment with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor) for metastatic disease. The administration of neoadjuvant or adjuvant therapy is allowed as long as it has finalized >= 6 months before entering the study. Patients can have received radiotherapy as long as the irradiated lesion is not the only target lesion for evaluating response and as long as radiotherapy has been completed before initiating the study treatment (a 2-week period is recommended). 2. Treatment with an investigational drug agent during the 3 weeks before enrollment in the study. 3. History of another neoplasm other than carcinoma in situ of the uterine cervix, basal cell skin carcinoma treated adequately, or prostate carcinoma with a good prognosis (Gleason <= 6) treated radically. History of another neoplasm treated curatively and without evidence of disease in the last 5 years. 4. Patients with symptomatic cerebral metastases. 5. Known hypersensitivity to erlotinib or any of its excipients. 6. Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sj�grens syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions. The use of contact lenses is not recommended during the study. The decision to continue to wear contact lenses should be discussed with the patient’s treating oncologist and the ophthalmologist. 7. Coumarins (Coumadin, warfarin) use. If the patient requires anti-coagulation therapy, the use of low molecular weight heparin instead of coumarins is recommended where clinically possible. 8. Unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease). 9. Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications. 10. Positive urine or serum pregnancy test in women of childbearing potential. Patients (male or female) with reproductive potential not willing to use effective method of contraception. Female patients should not be pregnant or breast-feeding. Oral or injectable contraceptive agents cannot be the sole method of contraception. 11. Patients with pre-existing parenchymal lung disease such as pulmonary fibrosis, lymphangiosis carcinomatosis. 12. Patients with known infection with HIV, HBV, HCV. Testing is not required in the absence of clinical signs and symptoms suggestive of these conditions. 13. Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol. 14. Incapacity to take oral medication or previous surgical procedures that affect absorption and imply the need for intravenous or parenteral feeding. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • 12- mounths progression-free survival |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Lo studio terminera` 12 mesi dopo che l`ultimo paziente sara` stato arruolato. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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