Assessment of the effect of a chemotherapy combining two molecules administred before surgery in patients with pancreas cancer

Phase 1

• Conditions: Potentially resectable pancreatic ductal adenocarcinoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003516-31-BE
• Lead Sponsor: CUB Erasme Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-18
• Last Update Posted: 21 July 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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;Secondary Objective: - 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);<br>- To compare the obtained data with those from the evaluation with gemcitabine alone.<br>;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.;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

Secondary Outcome Measures

Name	Time	Method
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;<br>- 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;<br>- Safety and feasibility of the whole therapeutic sequence (gemcitabine + Hh inhibitor + surgery<br>- Identification of predictive factors of response to anti-Hedgehog and gemcitabine;<br>- Disease-free survival (DFS) and overall survival (OS).<br>;Timepoint(s) of evaluation of this end point: Post surgery