| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced Non Small Lung Cancer unfit for a platinium-based chemotherapy |
| Fortgeschrittenes Nichtkleinzelliges-Bronchialkarzinom, ungeeignet für platinbasierte Chemotherapie |
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| E.1.1.1 | Medical condition in easily understood language |
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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 | 21.1 |
| 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) |
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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 Progression Free Survival (PFS) without Grade 4 toxicity (G4PFS) in both arms. This composite endpoint considers the first occurrence of either of the following:
- Grade 4 toxicity (lower grade AEs are not considered),
- Disease Progression or Death.
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| E.2.2 | Secondary objectives of the trial |
In both arms:
-To evaluate the Disease Control Rate without grade 4 toxicity,
-To evaluate the Disease Control Rate,
-To evaluate the Duration of Disease Control without grade 4 toxicity
-To evaluate the Duration of Disease Control,
-To evaluate the Objective Response Rate without grade 4 toxicity
-To evaluate the Objective Response Rate,
-To evaluate the Duration of Response,
-To evaluate Time to first response,
-To evaluate the Duration of Stable Disease,
-To evaluate the Progression-Free Survival without Grade 2-3-4 toxicity,
-To evaluate the Progression-Free Survival,
-To evaluate the Time To Treatment Failure,
-To evaluate the Overall Survival,
-To evaluate the Tolerance,
-To evaluate the Quality of Life.
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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 equal to 18 years.
-Histologically or cytologically confirmed NSCLC.
-ECOG Performance Status of 0-1 or 2,
-Advanced disease: stage IIIB (with supra-clavicular nodal metastases), stage IV or relapsing (locally or distant) after a local treatment. Patients not suitable for loco-regional treatment.
-Patients unfit for receiving a platinum-based chemotherapy based on at least one or more of the following criteria:
•Previous adjuvant platinum-based chemotherapy for resected NSCLC;
•Creatinine Clearance < 60 ml/min;
•Heart Failure NYHA class II-III;
•Hearing Loss > Grade 2;
•Medical condition impairing platinum-based chemotherapy according to physician’s opinion.
-Life expectancy more than 12 weeks.
-Adequate bone marrow, hepatic and renal functions:
•Neutrophils > or equal 2.0 x 109/l, Platelets > or equal 100 x 109/l, Haemoglobin > or equal 10.0 g/dL;
•Total bilirubin < or equal 1.5 x ULN (Upper Limit of Normal), Transaminases (ALT, AST) < 2.5 x ULN, Alkaline Phosphatases < 5 x ULN;
•Calculated creatinine clearance > or equal 30 ml/min (Cockcroft and Gault formula),
-Previous Therapy:
•Chemotherapy: no previous chemotherapy for advanced NSCLC. Patients may have been treated with adjuvant chemotherapy for completely resected NSCLC;
•Surgery: patients may have had previous surgery for NSCLC;
•Radiation therapy: patient may have received prior radiotherapy but not on the site used to assess response. A minimum of 2 weeks interval must have elapsed;
•Targeted therapy: patient with EGFR or ALK mutation may have had previous targeted therapy or immunotherapy.
-Presence of at least one measurable lesion which has not been previously irradiated (RECIST Version 1.1). Measurable lesions (measured in at least one dimension, longest diameter to be recorded) as > or equal 20 mm with conventional techniques or as > or equal 10 mm with CT scan. 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 randomisation 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 oral vinorelbine 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.
-Any important factor likely to modify drug absorption (e.g. surgery of the gastro-intestinal tract, significant malabsorption syndrome or disease affecting the gastro-intestinal 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 brain metastases except for the followings:
• Asymptomatic brain metastases which do not require local treatment in the opinion of the investigator;
• Brain metastases for which local treatment has been given: at least 4 weeks off corticosteroids and/or anti-convulsants treatment before study randomisation.
-Meningeal carcinomatosis.
-Symptomatic neuropathy (sensory) > or equal grade 2 according to the NCI Common Toxicity Criteria (NCI – CTC version 4.0).
-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, heart failure NYHA class III-IV, uncontrolled hypertension or arrhythmia, uncontrolled hypercalcaemia, active infection requiring i.v. antibiotics within 2 weeks before the beginning of treatment).
-Symptomatic ascite or pericardial effusion.
-Women if pregnant or lactating or with positive pregnancy test at inclusion; woman of child-bearing potential who did not use or is unwilling or unable to use an acceptable method of contraception to avoid pregnancy during the 2 months preceding the start of study treatment, for the entire study period and for up to 3 months after the last dose of oral vinorelbine.
-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.
-History of another malignancy within the past five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix.
-Concomitant treatment with another anticancer or any experimental drug within 30 days prior to treatment period.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) without Grade 4 toxicity (G4PFS) |
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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.
Safety will be assessed by:
-Physical examination including vitals signs, body weight and performance status.
-Complete blood cell count and serum biochemistry.
-Reporting adverse event using the NCI-CTC version 4.0 grading.
-Quality of Life Questionnaire (EORTC QLQ C30).
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| E.5.2 | Secondary end point(s) |
-To evaluate the Disease Control Rate without grade 4 toxicity,
-To evaluate the Disease Control Rate,
-To evaluate the Duration of Disease Control without grade 4 toxicity
-To evaluate the Duration of Disease Control,
-To evaluate the Objective Response Rate without grade 4 toxicity
-To evaluate the Objective Response Rate,
-To evaluate the Duration of Response,
-To evaluate Time to first response,
-To evaluate the Duration of Stable Disease,
-To evaluate the Progression-Free Survival without Grade 2-3-4 toxicity,
-To evaluate the Progression-Free Survival,
-To evaluate the Time To Treatment Failure,
-To evaluate the Overall Survival,
-To evaluate the Tolerance,
-To evaluate the Quality of Life.
|
|
| E.5.2.1 | 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.
Safety will be assessed by:
-Physical examination including vitals signs, body weight and performance status.
-Complete blood cell count and serum biochemistry.
-Reporting adverse event using the NCI-CTC version 4.0 grading.
-Quality of Life Questionnaire (EORTC QLQ C30).
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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 | Yes |
| E.6.13.1 | Other scope of the trial description |
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| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Navelbine with curently approved scheme |
|
| 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 | 50 |
| 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 |
| Austria |
| Czech Republic |
| Estonia |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Poland |
| Portugal |
| Romania |
| Singapore |
| Spain |
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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
|
| The end of study is defined as: 30 days following the last study drug administration of the last patient. No additional information will be collected from 30 days following the last study drug administration. |
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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 | 6 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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