Gene Therapy of Pancreatic Ductal Adenocarcinoma

Phase 1

Completed

• Conditions: Pancreatic Adenocarcinoma

• Registration Number: NCT01274455
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-10
• Study First Submitted QC: 2011-01-10
• Study First Posted: 2011-01-11
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-11
• Last Update Posted: 2016-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Feasability and security : Number of Participants with Adverse Events	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

Name	Time	Method
Antitumoral effect: secondary resecability, transgenes diffusion	60 days	antitumoral effect, secondary resecability, transgenes diffusion (urine and blood) and expression (tumor).

Trial Locations

Locations (1)

Toulouse Universitary Hospital (Rangueil), Department of Gastroenterology At Rangueil Hospital; 🇫🇷 Toulouse, France