Clinical trial NCT01274455: Gene Therapy of Pancreatic Ductal Adenocarcinoma
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Adenocarcinoma
Keywords: Gene therapy
pancreatic carcinoma
gemcitabine
endoscopic ultrasound
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Clinical Research Center, Toulouse
name: CAYLA-INVIVOGEN
First posted: 2011-01-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Feasability and security : Number of Participants with Adverse Events
timeFrame: 60 days
Secondary outcomes:
measure: Antitumoral effect: secondary resecability, transgenes diffusion
timeFrame: 60 days
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Toulouse Universitary Hospital (Rangueil), Department of Gastroenterology At Rangueil Hospital
Study officials:
affiliation: University Hospital of Toulouse
name: Louis BUSCAIL, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: