Advanced (stage IIIB or IV) NSCLC previously treated with 4 cycles of a platinum-based chemotherapy
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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). 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. - 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. - Previous adjuvant or neo-adjuvant treatment is permitted if completed >= 6 months before start of the chemotherapy phase. - ECOG performance status of 0 – 1. - Written (signed) Informed Consent for use of tumour samples. - Completion, of 4 cycles of an acceptable, standard, platinum based chemotherapy doublet without progression (i.e. CR, PR or SD). 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. - ECOG performance status of 0 - 1. - Life expectancy of at least 12 weeks. - Patients must be able to take oral medication. - 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. - Granulocyte count > 1,500/mm3 and platelet count > 100,000/mm3. Haemoglobin >= 9.0g/dl. - SGOT (AST) and SGPT (ALT) = 2.5 x ULN, SGOT (AST) and SGPT (ALT) must be = 2.5 x ULN in the presence of liver metastases, SGOT and SGPT must be 60 ml/min. - Normal serum calcium. - For all females of childbearing potential a negative pregnancy test must be obtained within 48 hours before starting Tarceva/placebo treatment. - Male and Female patients with reproductive potential must use 2 effective methods of contraception. - Age 18 (or legal age of consent if greater than 18) or greater. - Able to comply with study and follow-up procedures. - Written (signed) Informed Consent to participate in the randomised part of the study. - Patients must be able to effectively read, and understand the local language(s) for which the FACT-L questionnaires are available. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - No prior exposure to agents directed at the HER axis (e.g. gefitinib, cetuximab, trastuzomab). - No 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. - Patients who have undergone complete tumour resection after responding to platinum based chemotherapy. - 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. - Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer). - 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. - Patients who are at risk (in the investigator’s opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids are excluded. - Any inflammatory changes of the surface of the eye. - Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease. - Nursing and/or pregnant women. - Hypersensitivity to erlotinib (Tarceva) or to any of the excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 1. To compare overall survival between the treatment arms for 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.;Primary end point(s): The primary efficacy variable is duration of progression free survival (PFS), defined as the time from randomisation to disease progression or death whichever occurs first. | — |
Countries
Czech Republic, Denmark, Germany, Greece, Hungary, Italy, Lithuania, Portugal, Slovenia, Spain, United Kingdom
Outcome results
None listed