E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with: -Histologically or cytologically confirmed NSCLC (stage IIIB or IV) and -epidermal growth factor receptor (EGFR) positive mutation and -previously treated with tyrosine kinase inhibitor (gefitinib or erlotinib)
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E.1.1.1 | Medical condition in easily understood language |
Patients with lung cancer and epidermal growth factor receptor (EGFR) positive mutation, previously treated with tyrosine kinase inhibitor |
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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 | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10029515 |
E.1.2 | Term | Non-small cell lung cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 disease control rate (CR, PR, SD) of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy and safety parameters : The Duration of Disease Control, The Objective Response Rate and Duration of Response, The Time to First Response, Duration of Stable Disease, The Progression-Free Survival (PFS), Time To Treatment Failure (TTF), The Overall Survival (OS), The tolerance in the setting of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The patient must give written (personally signed and dated) informed consent before completing any study-related procedure. - Patients > or = 18 years. - Histologically or cytologically confirmed NSCLC. - Patients with epidermal growth factor receptor (EGFR) positive mutation. - Patients progressing or relapsing after treatment with EGFR tyrosine kinase inhibitors but a minimum of 2 weeks must have elapsed prior to start of study treatment. - Performance status KPS > or = 70% (ECOG/WHO PS 0-1). - Stage IIIB (with supra-clavicular nodal metastases), stage IV. - Life expectancy more than 12 weeks. - Adequate bone marrow, hepatic and renal functions: Neutrophils > or = 2.0 x 10^9/l, Platelets > or = 100 x 10^9/l, Haemoglobin > or = 10.0 g/dL; Total bilirubin < or = 1.5 x ULN (Upper Limit of Normal), Transaminases (ALT, AST) < 2.5 x ULN, Alkaline Phosphatases < 5 x ULN; Calculated creatinine clearance > or = 40 ml/min (Cockcroft and Gault formula). - Prior therapy: Chemotherapy: patient must not have had systemic chemotherapy or immunotherapy (monoclonal antibody); Radiation therapy: patient is eligible if presence of target lesions outside the irradiated area. A minimum of 4 weeks must have elapsed prior to start of study treatment. - Presence of at least one measurable lesion (measured in at least one dimension) which has not been previously irradiated (RECIST criteria – version 1.1). Physical examination and ultrasound will not be considered as objective tumour assessments. - Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial. - Women of childbearing potential must be using a medically accepted method of contraception (i.e. oral contraceptives, intrauterine devices) to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment in such a manner that the risk of pregnancy is minimised. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study treatment. - Fertile men must be using an effective method of birth control if their partners are women of childbearing potential throughout the study period and for up to 3 months after the last dose of study treatment. - The patient must have access to social insurance according to local regulations. |
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E.4 | Principal exclusion criteria |
Patients with at least one of the following criteria will not be included: - Known hypersensitivity to the study drug or to drugs with similar chemical structures. - Participation in another clinical trial with any experimental drug within the 30 days before registration and/or during the study. - Any important factor likely to modify drug absorption (e.g. surgery of the gastrointestinal tract, significant malabsorption syndrome or disease affecting the gastrointestinal tract function). - Previous radiotherapy in the only site used to assess response. - Clinically relevant or unstable systemic disease making implementation of the protocol difficult. - Active central nervous system disorder, brain metastasis or leptomeningeal involvement. - Symptomatic neuropathy (sensory) > or = grade 2 according to the NCI Common Toxicity Criteria (NCI – CTC version 2). - Weight loss > 10% within the previous 3 months. - Long term oxygen therapy. - Concomitant/uncontrolled medical disorder (cardiac failure or myocardial infarction within the previous 3 months, uncontrolled hypertension or arrhythmia, uncontrolled hypercalcaemia, active infection requiring i.v. antibiotics within 2 weeks before the beginning of treatment). - Women if pregnant or lactating or with positive pregnancy test at inclusion; - Women of childbearing potential who did not use or is unwilling or unable to use an acceptable method to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment. - Sexually active fertile men not using effective method of birth control method throughout the study period and for up to 3 months after the last dose of study treatment if his partner is a woman of childbearing potential. - Other malignancies except adequately treated basal carcinoma of the skin, in-situ cervix carcinoma or any other tumor with a disease free interval > 5 years. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the disease control rate (CR, PR, SD) of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour assessment will be performed according to the RECIST guideline (version 1.1). Assessment of measurable disease will be carried out at baseline and every 6 weeks until disease progression. |
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E.5.2 | Secondary end point(s) |
To evaluate efficacy and safety parameters - the response rate. - the duration of the disease control, the duration of response, the Time to Treatment Failure (TTF). - the Progression Free Survival (PFS) and Overall Survival (OS). - the tolerance in this setting
of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Singapore |
Taiwan |
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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
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The end of the study period is defined as the date of last progression observed in the study. Survival information will be collected approximately every 3 months until death.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |