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Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Neoadjuvant Chemotherapy Combining Gemcitabine and a Hedgehog Inhibitor (Vismodegib) in Patients With Resectable Pancreatic Adenocarcinoma

Phase 0
18 Years
Not Enrolling
Pancreatic Adenocarcinoma Resectable

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Trial Information

Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Neoadjuvant Chemotherapy Combining Gemcitabine and a Hedgehog Inhibitor (Vismodegib) in Patients With Resectable Pancreatic Adenocarcinoma

Pancreatic cancer is characterized by a high stromal density and is a hypoperfused tumor,
precluding cytotoxics delivery to the epithelial tumoral compartment. There is thus a
rationale for combining chemotherapy and antistromal drugs like Hedgehog inhibitors.
Targeting the resectable primary tumor offers an appropriate setting to (1) evaluate and
monitor early treatment effects on the tumor, (2) correlate dynamic imaging changes
(perfusion and diffusion coefficient) to pre- and post-therapeutic tissue changes, (3)
identify specific predictive biomarkers for the drugs used (i.e. gemcitabine transporters
and Hedgehog pathway genes and proteins) and (4) assess if this early "dynamic and
biomolecular response" can predict treatment benefit and patient outcome.

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 (Cockcroft 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;

- Signed written informed consent.

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 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;Subject previously
enrolled into this study.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

"Dynamic" tumor response rate as defined by a 20% modification of tumoral perfusion and cellular density parameters.

Outcome Description:

In order to detect changes in the tumor microenvironment and to monitor treatment efficacy, Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) constitute tools more and more used. The acquired data can be analyzed using a pharmacokinetic model to obtain quantitative parameters relative to tissue perfusion and vascular permeability (Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space; Apparent Diffusion Coefficient as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved weekly before each neoadjuvant chemotherapy treatment and before surgery. Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.

Outcome Time Frame:

4 weeks (duration of the neoadjuvant chemotherapy).

Safety Issue:


Principal Investigator

Jean-Luc Van Laethem, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Erasme University Hospital


Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:




Start Date:

December 2012

Completion Date:

December 2016

Related Keywords:

  • Pancreatic Adenocarcinoma Resectable
  • Pancreas
  • Cancer
  • Hedgehog inhibitor
  • Neoadjuvant chemotherapy
  • Dynamic imaging
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous