Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Vismodegib Before Surgery in Pancreatic Cancer

NCT ID: NCT01713218

Last Updated: 2012-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

EARLY_PHASE1

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pancreatic Adenocarcinoma Resectable

Keywords

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Pancreas Cancer Hedgehog inhibitor Neoadjuvant chemotherapy Dynamic imaging

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gemcitabine+Vismodegib

Neoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery

Group Type EXPERIMENTAL

gemcitabine

Intervention Type DRUG

Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4

Vismodegib

Intervention Type DRUG

150 mg capsule, oral, once daily

Neoadjuvant chemotherapy

Intervention Type PROCEDURE

Combination of gemcitabine and Vismodegib during a window interval (4 weeks) before surgery

Interventions

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gemcitabine

Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, week 1 to 4

Intervention Type DRUG

Vismodegib

150 mg capsule, oral, once daily

Intervention Type DRUG

Neoadjuvant chemotherapy

Combination of gemcitabine and Vismodegib during a window interval (4 weeks) before surgery

Intervention Type PROCEDURE

Other Intervention Names

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GEMZAR GDC-0449

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

Jean-Luc Van Laethem

OTHER

Sponsor Role lead

Responsible Party

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Jean-Luc Van Laethem

MD, PhD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Jean-Luc Van Laethem, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasme University Hospital

Locations

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Antwerp University Hospital (UZA)

Edegem, Antwerpen, Belgium

Site Status

Erasme University Hospital (ULB)

Brussels, , Belgium

Site Status

Countries

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Belgium

Central Contacts

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Jean-Luc Van Laethem, MD, PhD

Role: CONTACT

Email: [email protected]

Facility Contacts

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Marc Peeters, MD,PhD

Role: primary

Jean-Luc Van Laethem, MD, PhD

Role: primary

Other Identifiers

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2012-003516-31

Identifier Type: -

Identifier Source: org_study_id