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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
"Dynamic" tumor response rate as defined by a 20% modification of tumoral perfusion and cellular density parameters.
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.
4 weeks (duration of the neoadjuvant chemotherapy).
Jean-Luc Van Laethem, MD, PhD
Erasme University Hospital
Belgium: Federal Agency for Medicinal Products and Health Products