Gene Therapy of Pancreatic Ductal Adenocarcinoma

NCT ID: NCT01274455

Last Updated: 2016-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2013-03-31

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.

Conditions

Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Therapy

Group Type: EXPERIMENTAL

Gene Therapy product CYL-02 = plasmid DNA pre-complexed to linear polyethylenimine encoding sst2 + dck::umk genes

Intervention Type: GENETIC

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.

Interventions

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.

Intervention Type: GENETIC

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Clinical Research Center, Toulouse

OTHER

Sponsor Role: collaborator

CAYLA-INVIVOGEN

UNKNOWN

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Louis BUSCAIL, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Toulouse

Locations

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

Toulouse, , France

Countries

France

Other Identifiers

0401401

Identifier Type: -

Identifier Source: org_study_id