| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Advanced (stage IIIB or IV) NSCLC previously treated with 4 cycles of a platinum-based chemotherapy. | | NSCLC avanzato (stadio III o IV) precedentemente trattato con 4 cicli di chemioterapia a base di platino. | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10061873 | | E.1.2 | Term | Non-small cell lung cancer | | E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) | |
| 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 determine if the administration of Tarceva after standard platinum based chemotherapy in the treatment of NSCLC results in improved Progression Free Survival (PFS) when compared to placebo. 1. In all patients. 2. In patients who are EGFR protein expression (IHC)positive. | | Determinare se la somministrazione di Tarceva dopo la chemioterapia standard a base di platino nel trattamento del NSCLC porta ad un aumento della sopravvivenza senza progressione (PFS) rispetto al placebo. 1. In tutti i pazienti. 2. Nei pazienti che sono positivi per l'espressione della proteina EGFR | |
| E.2.2 | Secondary objectives of the trial | | 1.To compare overall survival between the treatment armsfor all patients and for patients who are EGFR protein expression (IHC) positive. 2.To compare PFS between the treatment arms in patients who are EGFR protein expression (IHC) negative 3.To compare overall survival between the two treatment arms for patients who are EGFR protein expression (IHC) negative. 4.To perform exploratory evaluations of tumour-tissue for biological or genomic determinants of outcome, including EGFR and K-ras mutational status and EGFR and HER2 expression status and other downstream targets. 5.To compare time to symptom progression between the two treatment arms. 6.To evaluate the safety profile of administering Tarceva after a standard platinum based chemotherapy in the treatment of NSCLC. 7.To investigate by a population analysis approach the pharmacokinetics of Tarceva in the target population, including the influence of covariates and to provide posthoc estimates of exposure. | | 1.Confr.la sopravv generale tra i 2 gruppi di tratt per tutti i paz e per i paz che sono espressione proteina EGFR(IHC)positivi.2.Confr.il PFS tra i due gruppi di tratt nei paz che sono positivi per l'espressione della proteina EGFR.3.Confr.la sopravv generale tra i 2 gruppi di tratt per i paz che sono l'espressione proteina EGFR negativi.4.Eseguire valut esplorative del tessuto tumorale per det.i fattori biologici o genomici che possono influenzare l'esito,incluso lo stato mutazionale di EGFR e K-ras e lo stato di espressione di EGFR e HER2 e altri target a valle.5.Confr.il tempo diprogr dei sintomi tra i due gruppi di tratt.6.Valut il profilo di sicur.della sommin di Tarceva dopo la chemioterapia standard a base di platino nel tratt del NSCLC.7.Valut con un approccio di analisi della pop la PK di Tarceva nella pop target,inclusa l'influenza delle covariate e fornire stime posthoc di esposizione.Verrà valutata la relazione tra esposizione a erlotinib e parametri di sicur.e eff. | |
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives | PHARMACOGENETIC:
Vers:A - RG
Date:2005/07/04
Title:
Objectives:
| FARMACOGENETICA:
Vers:A - RG
Data:2005/07/04
Titolo:Roche Sample Repository Research Project in association with protocol BO18192.
Obiettivi:To obtain a single blood sample from consenting patients enrolled in associated study BO18192 for pharmacogenetic and genetic research analysis.
| |
| E.3 | Principal inclusion criteria | | Before Chemotherapy 1.Patients with histologically documented, locally advanced or recurrent (Stage IIIB and not amenable for combined modality treatment) or metastatic (Stage IV) non-small cell lung cancer and who meet the study selection criteria of Section ``After Chemiotherapy``. 2.Formalin-fixed, paraffin-embedded tumour tissue samples representative of the tumour will be provided to sponsor within 3 weeks of the patient starting chemotherapy. This Is A Mandatory Requirement For Study Entry. 3. Patients must have measurable disease according to the RECIST criteria (in addition to investigator review, all CT/MRI data will in addition be reviewed by a central reader as confirmatory process). NOTE: Patients who experience CR, PR or SD during chemotherapy are eligible for the Tarceva/placebo study. 4. Previous adjuvant or neo-adjuvant treatment is permitted if completed ≥ 6 months before start of the chemotherapy phase. 5. ECOG performance status of 0 ¿ 1. 6. Written (signed) Informed Consent for use of tumour samples. After Chemotherapy 1.Completion, of 4 cycles of an acceptable, standard, platinum based chemotherapy doublet without progression (i.e. CR, PR or SD), (see Section 4.5). This Is A Mandatory Requirement For Study Entry. A maximum interval of 21 days between end of the last chemotherapy cycle and randomisation will be allowed. 2. ECOG performance status of 0 - 1. 3.Life expectancy of at least 12 weeks. 4.Patients must be able to take oral medication. 5.At least 4 weeks since any prior surgery or radiotherapy. Patients who, in the opinion of the investigator, have fully recovered from surgery in less than 4 weeks may also be considered for the study. 6.Granulocyte count ≥ 1,500/mm3 and platelet count > 100,000/mm3. Haemoglobin ≥ 9.0g/dL. 7. SGOT (AST) and SGPT (ALT) < 2,5 x ULN in the absence of liver metastases or up to 5 x ULN in case of liver metastases. 8.Alkaline phosphatase (ALP) < 2,5 x ULN. If alkaline phosphatase is ≥ 2.5 x ULN, SGOT (AST) and SGPT (ALT) must be < 1.5 x ULN. If alkaline phosphatase is ≥ 2.5 x ULN in the presence of liver metastases, SGOT and SGPT must be < 5 x ULN. 9. Normal serum calcium. 10. For all females of childbearing potential a negative pregnancy test must be obtained within 48 hours before starting Tarceva/placebo treatment. 11.Male and Female patients with reproductive potential must use 2 effective methods of contraception. 12. Age 18 (or legal age of consent if greater than 18) or greater. 13. Able to comply with study and follow-up procedures. 14. Written (signed) Informed Consent to participate in the randomised part of the study. 15.Patients must be able to effectively read, and understand the local language(s) for which the FACT-L questionnaires are available. | | - | |
| E.4 | Principal exclusion criteria | | 1.Prior exposure to agents directed at the HER axis (e.g. gefitinib, cetuximab, trastuzumab). 2.Prior chemotherapy or therapy with systemic anti-neoplastic therapy (e.g., monoclonal antibody therapy) for advanced disease. Prior surgery and/or localised irradiation is permitted. 3.Serum creatinine > 1.5 ULN and/or creatinine clearance < 60 mL/min. 4.Patients who have undergone complete tumour resection after responding to platinum based chemotherapy. 5.Any unstable systemic disease (including active infections, significant cardiovascular disease, [including myocardial infarction within the previous year], any significant hepatic, renal or metabolic disease) metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medication(s) or that might affect the interpretation of the results or render the patient at high risk from treatment complications. 6.Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer). 7.Patients are excluded if they have brain metastasis or spinal cord compression that has not yet been definitively treated with surgery and/or radiation; previously diagnosed and treated CNS metastases or spinal cord compression without evidence of stable disease (clinically stable imaging) for at least 2 months will also cause patients to be excluded. 8.Patients who are at risk (in the investigator¿s opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids are excluded. 9.Any inflammatory changes of the surface of the eye. 10.Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease. 11.Nursing and/or pregnant women. 12.Hypersensitivity to erlotinib (Tarceva) or to any of the excipients. | | - | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Progression Free Survival (RECIST) | | Sopravvivenza senza Progressione RECIST) | |
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 | No |
| 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 | | La fine dello studio coincide con l`ultima visita dell`ultimo paziente. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 39 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 39 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
