E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with stage IIIB with pleural effusion or stage IV NSCLC with documented disease progression during or after completion of docetaxel-based treatment are eligible for the study. |
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E.1.1.1 | Medical condition in easily understood language |
Non Small Cell Lung Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Overall Response Rate (ORR), defined as the proportion of patients with complete or partial response according to RECIST version 1.1 [17]. Given that the objective response rate from randomized phase III trials with agents active in the second line setting ranges from about 7-10%[9,10,8,11,12], a minimum objective response rate of 8% will be required in order to consider that the drug is potentially active and requires further evaluation. |
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E.2.2 | Secondary objectives of the trial |
i) Time to response, defined as the time interval between the date of enrollment and the date of the criteria of complete or partial response are met for the first time. ii) Disease control rate (DCR), defined as the proportion of patients with complete response+ partial response + stable disease. iii) Progression free survival (PFS), defined as the time interval between the date of enrollment and the date of disease progression or death (any cause). iv) Overall survival (OS), defined as the time interval between the date of enrollment and the date of death. v) Toxicity profile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Age>18 years old -Cytologically or histologically documented NSCLC -PS 0-2 (WHO scale) -Measurable disease according to RECIST v1.1 (at least one measurable lesion) -Documented disease progression to previous treatment with docetaxel regimen in 1st or 2nd line setting assessed by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) with at least one visceral or soft-tissue metastatic lesion. -Brain metastases are allowed, given that are clinically stable and the patient does not present neurologic symptoms. -Previous radiotherapy, either in the adjuvant setting or for the treatment of bone metastases, is allowed provided that the measurable lesions are outside the radiation fields. Patients who were irradiated to ≥ 40% of bone marrow are not eligible for the study. -Patients must have a recent (within 7 days prior to treatment start) biochemical and hematogical assessment as defined by adequate bone marrow (absolute neutrophil count ≥1.5 x 109 cells/L, platelets ≥100 x 109cells/L and hemoglobin ≥9 g/dL), liver (AST&ALT ≤ 2.5x ULN, total bilirubin within normal range) and renal (serum creatinine < 1.5 x ULN). If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded) function tests.[18] -Performance status 0-2 (WHO scale) -Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. -Before patient enrollment, written informed consent must be given according to ICH/GCP and national/local regulations. |
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E.4 | Principal exclusion criteria |
-Persistence of clinically relevant treatment-related toxicities from previous chemotherapy or radiotherapy. -Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of treatment or concomitantly with this trial. -Other malignancy within the past five years other than basal cell skin cancer or carcinoma in situ of the cervix. -Patient with reproductive potential not implementing accepted and effective method of contraception -History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs or to docetaxel - Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus, hypertension, heart failure ≤ NYHA II, history of myocardial infarction within the past 6 months, angina, chronic obstructive pulmonary disease (COPD), serious infections requiring systemic antibiotic therapy (e.g. antimicrobial, antifungal, antiviral) -Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix A and B) - Prior surgery, radiation, chemotherapy, within 4 weeks prior to treatment - Active grade ≥2 peripheral neuropathy - Active grade ≥2 stomatitis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (ORR), defined as the proportion of patients with complete or partial response according to RECIST version 1.1 [17]. Given that the objective response rate from randomized phase III trials with agents active in the second line setting ranges from about 7-10%[9,10,8,11,12], a minimum objective response rate of 8% will be required in order to consider that the drug is potentially active and requires further evaluation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 months after the first visit of the last patient |
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E.5.2 | Secondary end point(s) |
i) Time to response, defined as the time interval between the date of enrollment and the date of the criteria of complete or partial response are met for the first time. ii) Disease control rate (DCR), defined as the proportion of patients with complete response+ partial response + stable disease. iii) Progression free survival (PFS), defined as the time interval between the date of enrollment and the date of disease progression or death (any cause). iv) Overall survival (OS), defined as the time interval between the date of enrollment and the date of death. v) Toxicity profile |
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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 | 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 | No |
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 | 13 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |