Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Vismodegib Before Surgery in Pancreatic Cancer (NEOPACHI-001)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01713218
|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|