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Gene Therapy of Pancreatic Ductal Adenocarcinoma (TherGAP)

Primary Purpose

Pancreatic Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Gene Therapy product CYL-02 = plasmid DNA pre-complexed to linear polyethylenimine encoding sst2 + dck::umk genes
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Adenocarcinoma focused on measuring Gene therapy, pancreatic carcinoma, gemcitabine, endoscopic ultrasound

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient with a pancreatic adenocarcinoma histologically proven and/or a solid pancreatic mass associated with on or multiple metastatis from pancreatic origin (histologically proven)
  • Patient with a non resectable pancreatic adenocarcinoma (on preoperative CT-scan and/or endoscopic ultrasound evaluation)
  • Pancreatic tumor that could be evaluated by endoscopic ultrasound (no digestive stenosis, no gastrectomy)
  • Patient with no contraindication to général anaesthesia.
  • Karnofsky index >= 70%
  • Written informed consent given

Exclusion Criteria:

  • - Exclusion period for another clinical trial or research protocol.
  • Patient unable to read or understand information/consent formula or unable to decide alone for his participation to the trial
  • Patient under tutelage
  • Pregnant woman or able to procreate without contraception.
  • Patient with pancreatic cystic tumor or pancreatic pseudocyst.
  • Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastasis).

  • Patient contraindication to Gemzar® :

    • Hypersensitivity to Gemcitabine.
    • Decision of radiotherapy
    • Granulocytes < 1000/mm3
    • Thrombocytes < 100 000/mm3
  • Patient not efficiently treated for jaundice (biliary stent or bypass) if present at time of diagnosis
  • Contraindication for fine needle aspiration biopsy under endoscopic ultrasound (hemostasis trouble).

Sites / Locations

  • Toulouse Universitary Hospital (Rangueil), Department of Gastroenterology At Rangueil Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapy

Arm Description

Outcomes

Primary Outcome Measures

Feasability and security : Number of Participants with Adverse Events
Feasibility, security (pancreas and general) of intratumor injections of the gene therapy product (CYL-02 plasmid DNA pre-complexed to PEI encoding sst2 dck::umk) administered under endoscopic ultrasound guidance and followed by gemcitabine treatment at standard doses.

Secondary Outcome Measures

Antitumoral effect: secondary resecability, transgenes diffusion
antitumoral effect, secondary resecability, transgenes diffusion (urine and blood) and expression (tumor).

Full Information

First Posted
December 10, 2010
Last Updated
March 11, 2016
Sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France, Clinical Research Center, Toulouse, CAYLA-INVIVOGEN
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1. Study Identification

Unique Protocol Identification Number
NCT01274455
Brief Title
Gene Therapy of Pancreatic Ductal Adenocarcinoma
Acronym
TherGAP
Official Title
PILOT STUDY OF GENE THERAPY FOR LOCALLY ADVANCED PANCREATIC ADENOCARCINOMA WITH INTRATUMOURAL INJECTION OF JetPEI/DNA COMPLEXES WITH ANTITUMOURAL EFFECT AND CHEMOSENSITIZING ACTIVITY FOR GEMCITABINE
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France, Clinical Research Center, Toulouse, CAYLA-INVIVOGEN

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Near 85% of patients with pancreatic adenocarcinoma are diagnosed with a locally advanced and/or metastatic unresectable tumor. In these patients chemotherapy (such as gemcitabine) is given as a palliative therapy. Aim of the present study is to evaluate the feasibility, tolerance and antitumor effect of repeated intratumoral injection of a gene therapy product (with antitumor and chemo sensitizing effects) combined with gemcitabine in patients with unresectable pancreatic carcinoma.
Detailed Description
This is a gene therapy open non randomized phase I trial for advanced and/or metastatic pancreatic cancer patients. The protocol is based on the administration of increasing doses of a plasmid DNA pre-complexed to PEI (polyethylenimine - non-viral vector) that encodes two genes (somatostatin receptor subtype 2 named sst2 and deoxycitidine kinase :: uridylmonophosphate kinase named dck::umk) which exhibit complementary therapeutic effects. Both transgenes induce an antitumor bystander effect and render gemcitabine treatment more efficient. Intratumor injections of the gene therapy product (CYL-02) will be performed by transgastric or transduodenal route under endoscopic ultrasound guidance. Each injection will be followed standard gemcitabine IV administration every week (1000 mg/m2). Two intratumor injections of a same dose of CYL-02 will be administered at one month interval. Four increasing doses (125 µg, 250 µg, 500 µg and 1 mg) will be tested by group of 6 patients. The primary objectives are: evaluation of local pancreatic and general tolerance; the secondary objectives are: possible tumor volume regression, secondary respectability, evaluation of transgene biodistribution.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma
Keywords
Gene therapy, pancreatic carcinoma, gemcitabine, endoscopic ultrasound

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Therapy
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
Gene Therapy product CYL-02 = plasmid DNA pre-complexed to linear polyethylenimine encoding sst2 + dck::umk genes
Intervention Description
Intratumoral injection of the gene therapy product CYL-02 (2,5 ml within the primary tumor under endoscopic ultrasound guidance an under propofol anaesthesia). The intratumor injection of CYL-02 is followed by three IV infusions of Gemcitabine (1000 mg/m2) at 48 hours and then every two weeks. A second Intratumoral injection of the gene therapy product CYL-02 is performed at a same dosage and volume 30 days after the first administration followed by Three infusions of gemcitabine (1000 mg/m2) according the same rhythm (48 hours and every week) and dose.
Primary Outcome Measure Information:
Title
Feasability and security : Number of Participants with Adverse Events
Description
Feasibility, security (pancreas and general) of intratumor injections of the gene therapy product (CYL-02 plasmid DNA pre-complexed to PEI encoding sst2 dck::umk) administered under endoscopic ultrasound guidance and followed by gemcitabine treatment at standard doses.
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Antitumoral effect: secondary resecability, transgenes diffusion
Description
antitumoral effect, secondary resecability, transgenes diffusion (urine and blood) and expression (tumor).
Time Frame
60 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with a pancreatic adenocarcinoma histologically proven and/or a solid pancreatic mass associated with on or multiple metastatis from pancreatic origin (histologically proven) Patient with a non resectable pancreatic adenocarcinoma (on preoperative CT-scan and/or endoscopic ultrasound evaluation) Pancreatic tumor that could be evaluated by endoscopic ultrasound (no digestive stenosis, no gastrectomy) Patient with no contraindication to général anaesthesia. Karnofsky index >= 70% Written informed consent given Exclusion Criteria: - Exclusion period for another clinical trial or research protocol. Patient unable to read or understand information/consent formula or unable to decide alone for his participation to the trial Patient under tutelage Pregnant woman or able to procreate without contraception. Patient with pancreatic cystic tumor or pancreatic pseudocyst. Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastasis). Patient contraindication to Gemzar® : Hypersensitivity to Gemcitabine. Decision of radiotherapy Granulocytes < 1000/mm3 Thrombocytes < 100 000/mm3 Patient not efficiently treated for jaundice (biliary stent or bypass) if present at time of diagnosis Contraindication for fine needle aspiration biopsy under endoscopic ultrasound (hemostasis trouble).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louis BUSCAIL, MD,PhD
Organizational Affiliation
University Hospital of Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toulouse Universitary Hospital (Rangueil), Department of Gastroenterology At Rangueil Hospital
City
Toulouse
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Gene Therapy of Pancreatic Ductal Adenocarcinoma

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