Gene Therapy of Pancreatic Ductal Adenocarcinoma (TherGAP)

Toulouse University Hospital

Status and phase

Completed

Phase 1

Conditions

Pancreatic Adenocarcinoma

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT01274455

0401401

Details and patient eligibility

About

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.

Full 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.

Enrollment

22 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).