Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Vismodegib Before Surgery in Pancreatic Cancer (NEOPACHI-001)
|ClinicalTrials.gov Identifier: NCT01713218|
Recruitment Status : Unknown
Verified October 2012 by Jean-Luc Van Laethem, Erasme University Hospital.
Recruitment status was: Not yet recruiting
First Posted : October 24, 2012
Last Update Posted : October 24, 2012
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all human cancers and is considered as a sanctuary, resistant to most of the drugs used. Identification of new molecular targets involved in its pathogenesis is urgently needed and required both proper and innovative efficacy assessment.
This proof-of-concept trial is studying the "dynamic" tumor response after the administration of a short course (4 weeks) neoadjuvant combination of gemcitabine and a Hedgehog inhibitor (Vismodegib) before surgery in patients with operable pancreatic cancer.
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Adenocarcinoma Resectable||Drug: gemcitabine Drug: Vismodegib Procedure: Neoadjuvant chemotherapy||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Neoadjuvant Chemotherapy Combining Gemcitabine and a Hedgehog Inhibitor (Vismodegib) in Patients With Resectable Pancreatic Adenocarcinoma|
|Study Start Date :||December 2012|
|Estimated Primary Completion Date :||June 2014|
|Estimated Study Completion Date :||December 2016|
Neoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery
Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4
Other Name: GEMZAR
150 mg capsule, oral, once daily
Other Name: GDC-0449
Procedure: Neoadjuvant chemotherapy
Combination of gemcitabine and Vismodegib during a window interval (4 weeks) before surgery
- "Dynamic" tumor response rate as defined by a 20% modification of tumoral perfusion and cellular density parameters. [ Time Frame: 4 weeks (duration of the neoadjuvant chemotherapy). ]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.
- Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0. [ Time Frame: End of study follow-up (up to 2 years). ]Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine + Hedgehog inhibitor+ surgery).
- Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. [ Time Frame: 4 weeks (duration of the neoadjuvant chemotherapy). ]
- Effect of treatment on selected biomarkers in tumor resection specimens. [ Time Frame: 4 weeks (duration of the neoadjuvant chemotherapy). ]The objective is to identify within pre-therapeutic samples and surgical specimens several specific biomarkers involved (1) in the Hedgehog signalling pathway (GLI1, Sonic Hedgehog, Patched, Smoothened immunohistochemical patterns protein expression) and predicting response to anti-Hh therapy, (2) in the metabolization of gemcitabine (human equilibrative nucleoside transporter 1, deoxycytidine kinase) and predicting response to gemcitabine therapy, and (3) in the relative contribution of both anti-Hh therapy and gemcitabine therapy.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01713218
|Contact: Jean-Luc Van Laethem, MD, PhDemail@example.com|
|Antwerp University Hospital (UZA)||Not yet recruiting|
|Edegem, Antwerpen, Belgium, 2650|
|Contact: Marc Peeters, MD,PhD firstname.lastname@example.org|
|Principal Investigator: Marc Peeters, MD, PhD|
|Erasme University Hospital (ULB)||Not yet recruiting|
|Brussels, Belgium, 1070|
|Contact: Jean-Luc Van Laethem, MD, PhD email@example.com|
|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|