Resectable (cohort 1) and locally advanced or metastatic (cohort 2) pancreatic ductal adenocarcinoma
Conditions
Interventions
Trade Name: Abraxane
Product Name: Abraxane
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/m2 milligram(s)/squ
Sponsors
CUB Erasme Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
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=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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).;Secondary Objective: - 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).;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.;Timepoint(s | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. ;Timepoint(s) of evaluation of this end point: Cohort 1: post surgery Cohort 2: after at least 2 cycles of therapy | — |
Countries
Belgium
Contacts
Public ContactJean-Luc Van Laethem
CUB Erasme Hospital
Outcome results
None listed