Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Pancreatic Cancer (NEOPAX-001)
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with conventional treatments having little impact on disease course. Novel approaches are urgently needed to address inherent resistance to the current therapies and to identify new drugs or combinations that will have a high chance of success in pancreatic cancer patients. This proof-of-concept trial is studying the "dynamic" tumor response after the administration of a short course of gemcitabine and nab-paclitaxel (Abraxane) (a) during a window interval (4 weeks= 1 cycle) before surgery in resectable pancreatic cancer (cohort 1 = 21 patients) and (b) during at least 8 weeks (2 cycles) in locally advanced or metastatic pancreatic cancer (cohort 2 = 10 patients).
Pancreatic Adenocarcinoma Resectable
Pancreatic Adenocarcinoma Locally Advanced
Pancreatic Adenocarcinoma Metastatic
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Dynamic tumor response rate as defined by a 40% modification of tumoral perfusion and cellular density parameters. [ Time Frame: 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) ] [ Designated as safety issue: No ]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.
- Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine+Abraxane+surgery for resectable patients; gemcitabine+Abraxane for locally advanced/metastatic patients)
- Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 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) ] [ Designated as safety issue: No ]
- Effect of treatment on selected biomarkers in tumor resection specimens (cohort 1) and in case of obtaining tissue by Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) (cohort 2) [ Time Frame: 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) ] [ Designated as safety issue: No ]Evaluation of biomarkers involved in gemcitabine and nab-paclitaxel activity : human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), secreted protein acidic and rich in cysteine (SPARC), taxanes-related biomarkers.
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Chemotherapy combining gemcitabine and Abraxane during 4 weeks (1 cycle) before surgery (cohort 1: resectable patients) and during at least 8 weeks (2 cycles or more in case of response of stable disease) (cohort 2: locally advanced and metastatic patients)
Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)
Other Name: GEMZARDrug: Abraxane
Administrated intravenously at a dose of 125 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)
Other Name: nab-paclitaxel
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 tumors.
|Contact: Jean-Luc Van Laethem, MD, PhDfirstname.lastname@example.org|
|Antwerp University Hospital (UZA)||Not yet recruiting|
|Edegem, Antwerpen, Belgium, 2650|
|Contact: Marc Peeters, MD,PhD email@example.com|
|Principal Investigator: Marc Peeters, MD, PhD|
|Erasme University Hospital (ULB)||Not yet recruiting|
|Brussels, Belgium, 1070|
|Contact: Jean-Luc Van Laethem, MD, PhD firstname.lastname@example.org|
|Principal Investigator: Jean-Luc Van Laethem, MD, PhD|
|Sub-Investigator: Raphaël Maréchal, MD, PhD|
|Sub-Investigator: Anne Demols, MD, PhD|
|Principal Investigator:||Jean-Luc Van Laethem, MD, PhD||Erasme University Hospital|