E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Potentially resectable pancreatic ductal adenocarcinoma |
Adénocarcinome ductal pancréatique potentiellement résécable |
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E.1.1.1 | Medical condition in easily understood language |
Operable pancreatic cancer |
Cancer du pancréas opérable |
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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 |
To evaluate the “dynamic” tumor response by DCE-MRI and tumor modifications after the administration of a short course (4 weeks) neoadjuvant combination of gemcitabine and Vismodegib before surgery |
Evaluer la réponse tumorale "dynamique" par DCE-MRI et les modifications tumorales après l'administration d'une courte thérapie néoadjuvante (4 semaines) combinant gemcitabine et Vismodegib avant chirurgie |
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E.2.2 | Secondary objectives of the trial |
- To identify new targets involved in the Hedgehog signaling pathway and new biomarkers predicting response to anti Hh therapy (and the relative contribution of both anti-Hh therapy and gemcitabine therapy);
- To compare the obtained data with those from the evaluation with gemcitabine alone.
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- Identifier de nouvelles cibles impliquées dans la voie de signalisation hedgehog, et de nouveaux biomarqueurs prédictifs de la réponse aux anti-hedgehog (et la contribution relative de la thérapie anti-hedgehog et de la thérapie à base de gemcitabine);
- comparer les données obtenues avec celles obtenues avec de la gemcitabine en monothérapie |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histo(cyto)logically proven ductal pancreatic adenocarcinoma;
• Resectable or potentially resectable tumor; resectability assessed during a multidisciplinary meeting with expert surgeon and radiologist;
• First line chemotherapy;
• Age > 18 years;
• WHO performance status (PS) grade 0 or 1;
• Absolute neutrophil count > 1.5 x 10 9 / L, platelets > 100 x 10 9/ L, creatinine clearance (Cockroft and Gault formula) > 60 ml/min, haemoglobin level > 10 g/dl (transfusions authorized), bilirubin<1.5 g/dl;
• Optimal biliary drainage;
• Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation of who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum or urine pregnancy test prior to treatment. All WCBP, all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study;
• Written informed consent.
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E.4 | Principal exclusion criteria |
• Locally advanced non resectable or metastatic pancreatic adenocarcinoma;
• Previous anticancer therapy for the pancreatic adenocarcinoma;
• Biliary obstruction without endoscopic biliary drainage;
• Any contre-indication for surgery;
• Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the uterine cervix treated with a curative intent and any other tumor in CR with a disease-free interval > 3 years);
• Uncontrolled congestive heart failure or angina pectoris, myocardial infarction within 1 year prior to study entry, uncontrolled hypertension (systolic pressure > 160 mm or diastolic pressure > 100 mm under well conducted antihypertensive treatment), QT prolongation;
• Major uncontrolled infection;
• Severe hepatic impairment;
• Any medical, psychological, or social condition, which, in the opinion of the investigator, could hamper patient’s compliance to the study protocol and/or assessment/interpretation of the data;
• Pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods;
• Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study;Subject previously enrolled into this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
“Dynamic” tumor response rate after preoperative treatment exposure, which is defined by a 20% modification of tumoral perfusion status determined by quantitative DCE/DW-MRI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, Week 1 (pre-gemcitabine chemotherapy infusion n°1), Week 2 (pre-gemcitabine chemotherapy infusion n°2), , Week 3 (pre-gemcitabine chemotherapy infusion n°3), Week 4 (pre-gemcitabine chemotherapy infusion n°4), Day before surgery |
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E.5.2 | Secondary end point(s) |
- Correlation between tumoral changes (stromal, microvascular, epithelial components) on pathologic samples (pre and post therapeutic) and quantitative parameters relative to perfusion tissue and apparent diffusion coefficient (ADC) determined by DCE/DW-MRI;
- Evaluation of other efficacy markers in stromal and vascular microenvironment of tumor cells: decrease of the desmoplastic reaction, improvement of the microvascular density, downregulation of Hedgehog signalling pathway, modulation of stellate /cancer stem cells;
- Safety and feasibility of the whole therapeutic sequence (gemcitabine + Hh inhibitor + surgery
- Identification of predictive factors of response to anti-Hedgehog and gemcitabine;
- Disease-free survival (DFS) and overall survival (OS).
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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 | 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 | 2 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |