An Early Phase 1 interventional study of gemcitabine and Vismodegib in Pancreatic Adenocarcinoma Resectable, sponsored by Jean-Luc Van Laethem. Status unknown at 2 sites in Belgium. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-10-24.
Sponsored by Jean-Luc Van Laethem · Early Phase 1, Interventional, and Treatment
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.
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.
2,004 studies on the registry are indexed under Adenocarcinoma; 375 are open to participants now.
This study's planned enrollment of 21 is below the median of 45 across 1,553 interventional studies indexed under Adenocarcinoma.
Browse Adenocarcinoma studies →Jean-Luc Van Laethem is the lead sponsor of 2 studies on the registry; none are open to participants now.
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Neoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery
Drug: gemcitabine · Drug: Vismodegib · Procedure: Neoadjuvant chemotherapy
Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4
Also known as: GEMZAR
150 mg capsule, oral, once daily
Also known as: GDC-0449
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.
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.
Time frame: 4 weeks (duration of the neoadjuvant chemotherapy).
Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.
Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine + Hedgehog inhibitor+ surgery).
Time frame: End of study follow-up (up to 2 years).
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.
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.
Time frame: 4 weeks (duration of the neoadjuvant chemotherapy).
This study is status unknown, as verified in Oct 2012. You cannot join it, but the record below documents what was studied.
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Jean-Luc Van Laethem