E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced/metastatic pancreatic cancer |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033610 |
E.1.2 | Term | Pancreatic carcinoma metastatic |
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 |
The objective is to compare efficacy and safety of masitinib at 9 mg/kg/day in combination with gemcitabine, to placebo in combination with gemcitabine, in treatment of patients with advanced/metastatic pancreatic cancer.
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E.2.2 | Secondary objectives of the trial |
During this study, an ancillary pharmacogenomic study will be performed in order to define predictive criteria of efficacy (all efficacy variables: survival and tumor assessment) from genomic data.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Chemo naïve patient with advanced/metastatic disease
3. Documented decision justifying non eligibility for surgical resection. The documentation of the non eligibility for surgical resection will be reviewed by an independent committee.
4. Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST criteria
5. ECOG ≤ 1
6. Patient with a BMI > 18 kg/m² and weighing at least 40kg
7. Patient with organ function as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 10 g/dL
• Platelets ≥ 100 x 109/L
• AST/ALT ≤ 2.5x ULN (≤ 5 x ULN in case of liver metastases)
• GammaGT < 3 x ULN (< 5 x ULN in case of liver metastases)
• Bilirubin ≤ 1.5x ULN (≤ 3 x ULN in case of hepatic metastases)
• Creatinin clearance ≥ 50 mL/min (Cockcroft and Gault formula)
• Albuminemia ≥ 1 x LLN (32g/L)
• Urea ≤ 2 x ULN
• Proteinuria < 30 mg/dL on the dipstick; in case of proteinuria ≥ 30 mg/dL, 24-hour proteinuria should be < 1.5g/24 hours
8. Patient with life expectancy > 12 weeks |
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E.4 | Principal exclusion criteria |
1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ
2. Patient with, or with history, of central nervous system (CNS) metastasis
3. Patient with an abnormal cardiac function as defined as:
a. Medical history of myocardial infarction
b. Medical history of cardiac failure defined as a LVEF < 50% and/or a current treatment for cardiac failure,
c. Severe arrhythmia/conduction disorders, defined as severe ventricular arrhythmia; atrioventricular block at second or third level and/or left bundle branch block. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analyses will be conducted after all patients will have been followed for 12 months (corresponding to 252 events) |
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E.5.2 | Secondary end point(s) |
Tumor assessment:
· OS rate every 6 months
· Progression Free Survival (PFS).
· Time to Progression (TTP)
· Objective response rate (CR + PR) and control disease rate (CR + PR + SD) at week 24, 48
and 72
· Best response along study
· Level of serum CA 19-9 at week 24, 48 and 72 |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 40 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Czech Republic |
France |
Lebanon |
Poland |
Romania |
United States |
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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
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Patients will be treated untill disease progression |
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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 | 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 |