| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
First line Locally Advanced or Metastatic Non-Small-Cell Lung Cancer patients with
squamous histological type |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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) |
|
| 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 in both arms) on the whole study period (combination and maintenance periods). |
|
| E.2.2 | Secondary objectives of the trial |
- Estimation of DCR at the end of combination period,
- Estimation of Objective Response Rate on the whole study period,
- Estimation of Objective Response Rate at the end of combination period,
- Estimation of Duration of Disease Control,
- Estimation of Duration of Response,
- Estimation of Duration of Stable Disease,
- Estimation of Progression-Free Survival,
- Estimation of Time To Treatment Failure,
- Estimation of Overall Survival.
- Estimation of Tolerance.
- Estimation of Quality of Life (LCSS questionnaire)
- Estimation of Satisfaction Questionnaire. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients must satisfy all the following inclusion criteria before they are allowed to participate in the study:
- patient must give written informed consent.
- Chemo-naive patients superior or equal to 18 years
- Performance status KPS superior or equal to 70% (ECOG/WHO PS 0-1)
- Squamous histologically or cytologically (fine needle aspiration is acceptable) proven non-small cell lung cancer.
- 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.
- Life expectancy more than 12 weeks.
- Adequate bone marrow, hepatic and renal functions:
· Neutrophils superior or equal to 2.0x109/l, platelets superior or equal to 100x109/l, Haemoglobin superior or equal to 10 g/dl or 6.2 mmol/l.
· Total bilirubin inferior or equal to 1.5xULN, Transaminases < 2.5xULN, Alkaline Phosphatases < 5xULN (upper Limit of Normal).
· Creatinine < ULN (if limit value, creatinine clearance superior or equal to 60 ml/min).
- Prior therapy:
· Surgery: patients may have had previous surgery for NSCLC.
· Chemotherapy: patients must not have had systemic chemotherapy or immunotherapy.
· Radiation therapy: patient may have received prior radiotherapy but not on the site used to assess response. A minimum of 4 weeks interval must have elapsed.
- Presence of at least one measurable lesion which has not been previously irradiated (RECIST criteria. Version 1.1). Measurable lesions (measured in at least one dimension, longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 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 or up to 6 months after the last dose of cisplatin 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 during study period and up to 3 months following the last dose of oral vinorelbine or up to 6 months following the last dose of cisplatin or gemcitabine.
- The patient must have access to social insurance according to local regulations. |
|
| E.4 | Principal exclusion criteria |
Patients with at least one of the following criteria will not be included:
- Known hypersensitivity to the study drug(s) or to drugs with similar chemical structures.
- Any important factor likely to modify drug absorption, e.g. surgery of gastro-intestinal tract, significant malabsorption syndrome or disease affecting the gastro-intestinal tract function.
- Patients with a local relapse, which is liable to be treated by radiation therapy.
- Previous radiotherapy in the only site used to assess response.
- Radiotherapy within the previous 4 weeks.
- Active central nervous system disorder, brain metastasis or leptomeningeal involvement.
- Symptomatic neuropathy (sensory) superior or equal to grade 2 according to the NCI Common Toxicity Criteria (NCI – CTC version 2).
- Concomitant/uncontrolled medical disorder (superior cava vein syndrome, 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).
- Weight loss > 10% within the previous 3 months.
- Long term oxygen therapy.
- Symptomatic ascite or pericardial effusion.
- 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 the
treatment period.
- 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 or up to 6 months after the last dose of cisplatin.;
- Sexually active fertile man not using effective birth control during the study and up to 3 months following the last dose of oral vinorelbine or up to 6 months following the last dose of cisplatin or gemcitabine if his partner is a woman of child-bearing potential. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Disease Control Rate (Tumour assessment) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At baseline and every 6 weeks. After the completion of 4 cycles, in case of maintenance treatment, assessment will be performed every 6 weeks (2 cycles) until disease progression. |
|
| E.5.2 | Secondary end point(s) |
Efficacy endpoints will be assessed by tumour assessment.
Safety will be assessed by:
- Physical examination including vitals signs, body weight and performance status.
- Complete blood cell count (WBC, Neutrophils, Haemoglobin and platelet counts).
- Biochemistry.
- Reporting adverse event using the NCI-CTC version 2.0 grading.
- Quality of life questionnaire and satisfaction questionnaire. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety assessment will be performed at baseline, at each cycle, until end of study.
Quality of life will be assessed at baseline, cycles 3 and 4, and end of study |
|
| 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 | 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 5 |
| 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 |
|
| 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 the study period is defined as the date of last progression in the study. Survival information will be collected approximately every 6 weeks until progression and then approximately every 3 months until death or decision of closure. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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