NCT01713218

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
21

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Dec 2012

Longer than P75 for early_phase_1

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 17, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 24, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

December 1, 2012

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

October 24, 2012

Status Verified

October 1, 2012

Enrollment Period

1.5 years

First QC Date

October 17, 2012

Last Update Submit

October 22, 2012

Conditions

Pancreatic Adenocarcinoma Resectable

Keywords

PancreasCancerHedgehog inhibitorNeoadjuvant chemotherapyDynamic imaging

Outcome Measures

Primary Outcomes (1)

  • "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.

    4 weeks (duration of the neoadjuvant chemotherapy).

Secondary Outcomes (1)

  • Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.

    End of study follow-up (up to 2 years).

Other Outcomes (2)

  • Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

    4 weeks (duration of the neoadjuvant chemotherapy).

  • Effect of treatment on selected biomarkers in tumor resection specimens.

    4 weeks (duration of the neoadjuvant chemotherapy).

Study Arms (1)

Gemcitabine+Vismodegib

EXPERIMENTAL

Neoadjuvant chemotherapy combining gemcitabine and Vismodegib during 4 weeks before surgery

Drug: gemcitabineDrug: VismodegibProcedure: Neoadjuvant chemotherapy

Interventions

gemcitabineDRUG

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

Also known as: GEMZAR
Gemcitabine+Vismodegib
VismodegibDRUG

150 mg capsule, oral, once daily

Also known as: GDC-0449
Gemcitabine+Vismodegib
Neoadjuvant chemotherapyPROCEDURE

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

Gemcitabine+Vismodegib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Antwerp University Hospital (UZA)

Edegem, Antwerpen, 2650, Belgium

Location

Erasme University Hospital (ULB)

Brussels, 1070, Belgium

Location

MeSH Terms

Conditions

Neoplasms

Interventions

GemcitabineHhAntag691Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingCombined Modality TherapyTherapeutics

Study Officials

  • Jean-Luc Van Laethem, MD, PhD

    Erasme University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Luc Van Laethem, MD, PhD

CONTACT

jl.vanlaethem@erasme.ulb.ac.be

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

October 17, 2012

First Posted

October 24, 2012

Study Start

December 1, 2012

Primary Completion

June 1, 2014

Study Completion

December 1, 2016

Last Updated

October 24, 2012

Record last verified: 2012-10

Locations

BE(2)