Patient case: 49-year-old female with Pancreatic adenocarcinoma. Genetic variant: KRAS, TP53. Other conditions: None.

Clinical trial: Gene Therapy of Pancreatic Ductal Adenocarcinoma

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: 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).

Relevance to patient case: not relevant