Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Patients With Potentially Operable, Locally Advanced or Metastatic Pancreatic Adenocarcinoma
Pancreatic cancer is a hypoperfused tumor, characterized by a high stroma density precluding
cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for
combining chemotherapy and antistromal drugs like nab-paclitaxel (Abraxane), a solvent
(Cremophor® EL)-free, albumin-bound form of paclitaxel that has been initially developed to
reduce the toxicities associated with Taxol injection while maintaining or improving its
chemotherapeutic effect. This unique protein formulation provides a novel approach of
increasing intra-tumoral concentrations of the drug by a receptor-mediated transport process
allowing transcytosis across the endothelial cell.
Abraxane has been approved for commercialization in 38 countries, including the US, Canada,
the EU, Australia, China, India and Korea for the treatment of women with metastatic breast
cancer. Abraxane alone and in combination is being evaluated in a number of cancers,
including metastatic melanoma, non-small cell lung cancer, pancreatic cancer and other solid
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dynamic tumor response rate as defined by a 40% 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 Coefficient Diffusion as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved before each chemotherapy treatment (and also before surgery for resectable patients). Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.
4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients)
Jean-Luc Van Laethem, MD, PhD
Erasme University Hospital
Belgium: Federal Agency for Medicinal Products and Health Products