E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Resectable (cohort 1) and locally advanced or metastatic (cohort 2) pancreatic ductal adenocarcinoma |
Adénocarcinome ductal pancréatique résécable (cohorte 1) et localement avancé ou métastatique (cohorte 2) |
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E.1.1.1 | Medical condition in easily understood language |
Operable (cohort 1) and locally advanced/metastatic (cohort 2) pancreas cancer |
Cancer du pancréas opérable (cohorte 1) et localement avancé ou métastatique (cohorte 2) |
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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 prospectively evaluate the performance of DCE/DW-MRI (Dynamic Contrast-Enhanced/Diffusion Weighted-Magnetic Resonance Imaging) in assessing the “dynamic” tumor response rate after the administration of a short course combination of gemcitabine and nab-paclitaxel (Abraxane) during (a) a window interval of 3 weeks (=1 cycle) before the planned surgery in resectable pancreatic cancer (cohort 1) and (b) at least two cycles in metastatic or locally advanced pancreatic cancer (cohort 2). |
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E.2.2 | Secondary objectives of the trial |
- to correlate the observed dynamic imaging parameters to the histopathological tumoral changes in order to further categorize patients subpopulations;
- to identify within pre-therapeutic samples and surgical specimens specific biomarkers involved (1) in the nab-paclitaxel activity (SPARC, taxanes-related biomarkers immunohistochemical patterns expression) and predicting response to Abraxane therapy, (2) in the intracellular uptake (hENT1) and activation (dCK) of gemcitabine and predicting response to gemcitabine therapy, and (3) in the relative contribution of both Abraxane and gemcitabine therapy;
- to compare the obtained data with those collected from the evaluation with gemcitabine alone in a similar protocol;
- to use the biomarkers and dynamic imaging-driven clinical platform parameters to properly define a “dynamic and biomolecular” response or non response to preoperative therapy, which would be able to predict the benefiters of such strategy (patient outcome). |
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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 (cohort 1), or locally advanced and/or metastatic tumor (cohort 2);
- 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 |
- 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 complete remission 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; patients 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 (a) gemcitabine and Abraxane preoperative treatment exposure (3 weeks= 1 cycle) for resectable pancreatic cancer (cohort 1) and (b) gemcitabine and Abraxane treatment exposure (at least 2 cycles) for metastatic or locally advanced pancreatic cancer (cohort 2). The dynamic tumor response rate will be defined by a 40% modification of tumoral perfusion status and/or ADC status determined by quantitative DCE/DW-MRI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cohort 1: Screening, Week 1 (before chemotherapy Week 1), Week 2 (before chemotherapy Week 2), Week 3 (before chemotherapy Week 3) and day before surgery.
Cohort 2: Screening and before each administration of chemotherapy |
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E.5.2 | Secondary end point(s) |
For cohort 1 (resectable primary tumor):
- Correlation between tumoral mean vessel density (MVD) counts evaluated by immunostaining with CD31 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 plasma Stromal Cell-Derived Factor-1 (SDF-1 level);
- Pathological evaluation of tumor changes (stroma, vascular density, stellate cells, stem cells, tumor regression);
- Evaluation of both markers of gemcitabine and nab-paclitaxel activity : nucleoside transporters hENT1, dCK, CDA, SPARC, taxanes-related biomarkers;
- Feasibility and toxicity of the whole therapeutic sequence (Abraxane + gemcitabine + surgery
For cohort 2 (locally advanced and/or metastatic lesions):
- Correlation with the RECIST response by CT or MRI obtained at 8 weeks;
- Stromal ( fibrosis) pattern evaluation between the primary and secondary lesions ( DCE/DW-MRI and pathological pattern if available);
- Idem cohort 1 in case of obtaining tissue.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cohort 1: post surgery
Cohort 2: after at least 2 cycles of therapy |
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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.8.3 |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |