- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01713218
Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Vismodegib Before Surgery in Pancreatic Cancer (NEOPACHI-001)
Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Neoadjuvant Chemotherapy Combining Gemcitabine and a Hedgehog Inhibitor (Vismodegib) in Patients With Resectable Pancreatic Adenocarcinoma
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Brussels, Belgium, 1070
- Erasme University Hospital (ULB)
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Antwerpen
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Edegem, Antwerpen, Belgium, 2650
- Antwerp University Hospital (UZA)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histo(cyto)logically proven ductal pancreatic adenocarcinoma
- Resectable or potentially resectable tumor; resectability assessed during a multidisciplinary meeting with expert surgeon and radiologist
- First line chemotherapy
- Age > 18 years
- WHO performance status (PS) grade 0 or 1;
- Absolute neutrophil count > 1.5 x 10 9 / L, platelets > 100 x 10 9/ L, creatinine clearance (Cockcroft and Gault formula) > 60 ml/min, haemoglobin level > 10 g/dl (transfusions authorized), bilirubin<1.5 g/dl;
- Optimal biliary drainage;
- Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation of who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum or urine pregnancy test prior to treatment. All WCBP, all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study;
- Signed written informed consent.
Exclusion Criteria:
- Locally advanced non resectable or metastatic pancreatic adenocarcinoma
- Previous anticancer therapy for the pancreatic adenocarcinoma
- Biliary obstruction without endoscopic biliary drainage
- Any contre-indication for surgery
- Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the uterine cervix treated with a curative intent and any other tumor in complete remission with a disease-free interval > 3 years)
- Uncontrolled congestive heart failure or angina pectoris, myocardial infarction within 1 year prior to study entry, uncontrolled hypertension (systolic pressure > 160 mm or diastolic pressure > 100 mm under well conducted antihypertensive treatment), QT prolongation
- Major uncontrolled infection
- Severe hepatic impairment
- Any medical, psychological, or social condition, which, in the opinion of the investigator, could hamper patient's compliance to the study protocol and/or assessment/interpretation of the data
- Pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods
- Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study;Subject previously enrolled into this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Gemcitabine+Vismodegib
Neoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery
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Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4
Other Names:
150 mg capsule, oral, once daily
Other Names:
Combination of gemcitabine and Vismodegib during a window interval (4 weeks) before surgery
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
"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).
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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.
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4 weeks (duration of the neoadjuvant chemotherapy).
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
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Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine + Hedgehog inhibitor+ surgery).
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End of study follow-up (up to 2 years).
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time Frame: 4 weeks (duration of the neoadjuvant chemotherapy).
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4 weeks (duration of the neoadjuvant chemotherapy).
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Effect of treatment on selected biomarkers in tumor resection specimens.
Time Frame: 4 weeks (duration of the neoadjuvant chemotherapy).
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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.
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4 weeks (duration of the neoadjuvant chemotherapy).
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gemcitabine
Other Study ID Numbers
- 2012-003516-31
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Lawson Health Research InstituteLondon Health Sciences FoundationNot yet recruitingBorderline Resectable Pancreatic Adenocarcinoma | Resectable Pancreatic Adenocarcinoma
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingBorderline Resectable Pancreatic Adenocarcinoma | Resectable Pancreatic Ductal Adenocarcinoma | Locally Advanced Pancreatic Ductal AdenocarcinomaUnited States
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HonorHealth Research InstituteActive, not recruitingLocally Advanced Pancreatic Adenocarcinoma | Borderline Resectable Pancreatic Adenocarcinoma | Untreated Resectable Pancreatic AdenocarcinomaUnited States
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Memorial Sloan Kettering Cancer CenterRecruitingPancreatic Cancer | Pancreatic Cancer Metastatic | Pancreatic Cancer Stage IV | Metastatic Pancreatic Carcinoma | Metastatic Pancreatic Adenocarcinoma | Pancreatic Carcinoma | Metastatic Pancreatic Cancer | Pancreatic Cancer Non-resectable | Metastatic Pancreatic Ductal Adenocarcinoma | Pancreatic Carcinoma... and other conditionsUnited States
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