Gene Therapy of Pancreatic Ductal Adenocarcinoma (TherGAP)

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Genetic: Gene Therapy product CYL-02 = plasmid DNA pre-complexed to linear polyethylenimine encoding sst2 + dck::umk genes

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • Toulouse Universitary Hospital (Rangueil), Department of Gastroenterology At Rangueil Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antitumoral effect: secondary resecability, transgenes diffusion	antitumoral effect, secondary resecability, transgenes diffusion (urine and blood) and expression (tumor).	60 days

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Clinical Research Center, Toulouse; CAYLA-INVIVOGEN
• Investigators: Principal Investigator: Louis BUSCAIL, MD,PhD, University Hospital of Toulouse

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 10, 2010
• First Submitted That Met QC Criteria: January 10, 2011
• First Posted (Estimate): January 11, 2011

Study Record Updates

• Last Update Posted (Estimate): March 14, 2016
• Last Update Submitted That Met QC Criteria: March 11, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: gemcitabine; endoscopic ultrasound; Gene therapy; pancreatic carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: 0401401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No