Pancreatic Adenocarcinoma
Conditions
Keywords
Gene therapy, pancreatic carcinoma, gemcitabine, endoscopic ultrasound
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.
Interventions
GENETICGene 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.
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Clinical Research Center, Toulouse
CAYLA-INVIVOGEN
University Hospital, Toulouse
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Antitumoral effect: secondary resecability, transgenes diffusion | 60 days | antitumoral effect, secondary resecability, transgenes diffusion (urine and blood) and expression (tumor). |
Countries
France
Outcome results
None listed