E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
No squamous non small cell lung |
|
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 | 18.0 |
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 |
Efficacy of the the nintedanib- docetaxel combination in second-line treatment in patients with no squamous non small cell lung cancer refractory to first line chemotherapy |
|
E.2.2 | Secondary objectives of the trial |
- To assess toxicities and feasibility
-To evaluate tolerability during treatment
- To assess overall survival, overall response rate, and quality of life
- To assess progression free survival in patients according to disease progression at 2 or 4 cycles of first line treatment
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed non-squamous NSCLC,
• Locally advanced and/or metastatic NSCLC of stage IV (according to American Joint Committee on Cancers) or recurrent NSCLC)
• Patients without activating EGFR mutation
• Patients without ALK rearrangement
• Patients must have measurable lesion by RECIST 1.1
• Refractory disease defined by documented progression during the first-line chemotherapy based on a platinum doublet and third-generation drug (four or less cycles) according to RECIST V.1.1
• Age ≥18 years and < 75 years
• Performance status (PS) 0-1 (WHO, Appendix C).
• Life expectancy of more than 12 weeks.
• No history of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
• No ongoing treatment related toxicity due to prior treatment > grade I (except alopecia).
• Adequate organ function, evidenced by the following laboratory results within 3 weeks prior to randomization: Normal hepatic function: bilirubin < 1.5 x N, ALAT and ASAT < 2.5 x N or <5 x N in case of liver metastasis
• Normal renal function (calculated creatinine clearance ≥ 45 mL/min).
• Normal Calcemia
• Normal haematological function (polynuclear neutrophils > 1.5 G/l, platelets > 100 G/l).
• Anticoagulation with a vitamin K antagonist and LMWH is authorized.
• Antiplatelet treatment (aspirin authorized if < 325 mg/d)
• Treatment with dipyridamole, ticlopidine, clopidogrel and/or cilostazol is not authorized
• Women of child bearing potential must use effective contraception.
• Men might be surgically sterile or accept to use an effective contraceptive procedure during and until 6 months after the treatment.
o Written informed consent to participate in the study.
|
|
E.4 | Principal exclusion criteria |
Known hypersensitivity to the trial drugs (nintedanib, docetaxel), to their excipients or to contrast media
• Controlled disease after first line treatment
• Contra indication to the use of the backbone treatment
• Patients who were withdrawn from first line treatment due to toxicity without documented disease progression or who received placebo (in the context of a clinical trial) as prior treatment are not eligible.
• Previous treatment with docetaxel
• Small-cell lung cancer, bronchioloalveolar cancer, neuroendocrine cancer.
• Previous therapy with VEGF inhibitors except bevacizumab
• Centrally located tumour with radiographic evidence of local invasion of local blood vessels
• Radiographic evidence of cavitary or necrotic tumours at screening
• Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug.
• Radiotherapy (except extremities) within the past 3 months prior to baseline imaging
• Persistence of clinically relevant therapy related toxicity from previous radiotherapy
• Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before inclusion).
• Uncontrolled arterial hypertension.
• Concurrent radiotherapy, except for palliative bone irradiation.
• Other concurrent severe illnesses (congestive heart failure, unstable angina, significant arrhythmia or myocardial infarction less than 12 months before study entry).
• Stroke less than 6 months before study entry.
• Psychiatric or neurological disorders preventing the patient from understanding the nature of the trial
• Grade 1 peripheral neuropathy
• Uncontrolled infection.
• Caval syndrome
• Other organic disorders preventing inclusion in the trial
• Malabsorption syndrome
• Pregnancy and breast-feeding
• Surgery less than two months before study entry.
• Follow-up not feasible.
• Incarcerated and institutionalized
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Median progression free survival at 12 weeks |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- To assess toxicities and feasibility
- To evaluate tolerability during treatment
- To assess overall survival, overall response rate, and quality of life
- To assess progression free survival in patients according to disease progression at 2 or 4 cycles of first line treatment.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
To evaluate tolerability during treatment: every 3 weeks
- To assess overall survival, overall response rate: at 12 month
-To assess and quality of life:every 6 weeks
- To assess progression free survival in patients according to disease progression at 2 or 4 cycles of first line treatment.
ach cycle |
|
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 | Yes |
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.8.3 |
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 | 30 |
E.8.5 | The trial involves multiple Member States | No |
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 | Yes |
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
|
|
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 |