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Gene Therapy of Pancreatic Ductal Adenocarcinoma (TherGAP)

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. Identifier: NCT01274455
Recruitment Status : Completed
First Posted : January 11, 2011
Last Update Posted : March 14, 2016
Institut National de la Santé Et de la Recherche Médicale, France
Clinical Research Center, Toulouse
Information provided by (Responsible Party):
University Hospital, Toulouse

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.

Condition or disease Intervention/treatment Phase
Pancreatic Adenocarcinoma Genetic: Gene Therapy product CYL-02 = plasmid DNA pre-complexed to linear polyethylenimine encoding sst2 + dck::umk genes Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : December 2010
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine

Arm Intervention/treatment
Experimental: Therapy Genetic: Gene Therapy product CYL-02 = plasmid DNA pre-complexed to linear polyethylenimine encoding sst2 + dck::umk genes
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 Measures :
  1. Feasability and security : Number of Participants with Adverse Events [ Time Frame: 60 days ]
    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 :
  1. Antitumoral effect: secondary resecability, transgenes diffusion [ Time Frame: 60 days ]
    antitumoral effect, secondary resecability, transgenes diffusion (urine and blood) and expression (tumor).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

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 identifier (NCT number): NCT01274455

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Toulouse Universitary Hospital (Rangueil), Department of Gastroenterology At Rangueil Hospital
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Institut National de la Santé Et de la Recherche Médicale, France
Clinical Research Center, Toulouse
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Principal Investigator: Louis BUSCAIL, MD,PhD University Hospital of Toulouse

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Responsible Party: University Hospital, Toulouse Identifier: NCT01274455     History of Changes
Other Study ID Numbers: 0401401
First Posted: January 11, 2011    Key Record Dates
Last Update Posted: March 14, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital, Toulouse:
Gene therapy
pancreatic carcinoma
endoscopic ultrasound

Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs