E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028997 |
E.1.2 | Term | Neoplasm malignant |
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 determine objective response rate (ORR). |
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E.2.2 | Secondary objectives of the trial |
To assess duration of response (DR), progression free survival (PFS) and overall survival (OS). To evaluate global safety profile. To determine pharmacokinetic profile. To assess clinical utility of fluorescence in situ hybridization (FISH) assay in selection of patients with mesenchymal-epithelial hybridization (MET) gene amplifcation. To assess lung cancer symptoms, health-related quality of life and treatment satisfaction. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Metastatic non-small-cell lung cancer patients with progressive disease during or after first or second line therapy harboring MET gene amplification and with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. |
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E.4 | Principal exclusion criteria |
Patient less than 18 years old. Eastern Cooperative Oncology Group (ECOG) performance status >2. More than 2 episodes of disease progression under anticancer therapy. Wash out period of less than 3 weeks from prior treatment with chemotherapy, radiotherapy or, surgery or any investigational treatment. Adequate hematologic, hepatic, renal, coagulation, and metabolic functions. No resolution of any specific toxicities (excluding alopecia) related to any prior anti-cancer therapy to grade ≤1 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03. Pregnant or breast-feeding women. Patient with reproductive potential without method of contraception. Symptomatic brain metastasis. Any clinically significant medical condition other than cancer which could interfere with the safe delivery of study treatment or risk of toxicity. Known hypersensitivity or any adverse event related to the study drug excipient (Captisol®). Prior treatment with any MET Tyrosine Kinase Inhibitors (TKIs) or anti-MET antibodies (excluding onartuzumab). Patients treated with potent CYP3A inhibitor unless it can be discontinued. Patients treated with potent and moderate CYP3A inducers unless it can be discontinued. Mean QTc interval prolongation >470 msec. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Determination of the objective response rate of SAR125844 as per RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 6 weeks up to disease progression |
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E.5.2 | Secondary end point(s) |
Progression-free survival rate Overall survival rate
Proportion of patients with adverse events
Assessment of pharmacokinetic parameters: maximum plasma concentration (Cmax) Assessment of pharmacokinetic parameters: area under curve (AUC) Assessment of pharmacokinetic parameters: total clearance (CL) Assessment of pharmacokinetic parameters: half-life (t1/2)
Assessment of lung cancer symptoms by Core Quality of Life questionnaire (QLQ-C30) +LC13 Assessment of health-related quality of life by QLQ-C30/LC13
Assessment of treatment satisfaction by Cancer Therapy Satisfaction Questionnaire
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 34 months Progression-free survival rate Overall survival rate
Up to 40 months Proportion of patients with adverse events
Up to 3 days Assessment of pharmacokinetic parameters: maximum plasma concentration (Cmax) Assessment of pharmacokinetic parameters: area under curve (AUC) Assessment of pharmacokinetic parameters: total clearance (CL) Assessment of pharmacokinetic parameters: half-life (t1/2)
Every 3 weeks up to 34 months Assessment of lung cancer symptoms by Core Quality of Life questionnaire (QLQ-C30) +LC13 Assessment of health-related quality of life by QLQ-C30/LC13
Every 6 weeks up to 34 months Assessment of treatment satisfaction by Cancer Therapy Satisfaction Questionnaire
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Lung Cancer symptoms, health-related quality of life, and treatment satisfaction |
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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 | 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 | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Romania |
Russian Federation |
Spain |
Turkey |
United States |
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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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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 | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |