Effect of Intratumoral Injection of Gene Therapy for Locally Advanced Pancreatic Cancer

• Status: Active, not recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries, and its incidence has increased over the last 40 years. Curative surgery to manage PDAC is possible in only a fraction of patients; indeed, a vast majority (85%) of patients is diagnosed with locally advanced tumors and/or metastases because they lack specific symptoms and early markers for this disease. For these patients, palliative armamentarium consists of conventional chemotherapeutic agents such as Gemcitabine and, more recently, FOLFIRINOX, which offer marginal survival benefits. Consequently, the prognosis for PDAC is still very poor and there is great need for new treatments that can change this poor outcome. In this context, the investigators have devised, in the past few years, a highly innovative approach based on therapeutic gene transfer, which does not rely on a specific genetic and/or cellular background to inhibit PDAC tumor growth. the investigators found that SSTR2 and DCK::UMK gene transfer demonstrated complementary therapeutic effects to inhibit tumor progression and dissemination, and reduced tumor burden, respectively. On the basis of these promising preclinical data, the investigators conducted past three years the first clinical study of non-viral vector-mediated therapeutic gene delivery, guided by endoscopy (EUS), and combined with standard Gemcitabine therapy in patients with locally advanced and metastatic PDAC. The phase 1 demonstrated that the gene-therapy product CYL-02 is expressed in PDAC tumors (with long-lasting expression within tumor tissues), is distributed within the bloodstream in some extent, when combined with Gemcitabine it can inhibit primary-tumor progression and dissemination. Our results tend to demonstrate therapeutic efficacy, especially in patients with locally advanced tumors. Based on these encouraging results, the investigators propose that patients with locally advanced PDAC at the time of diagnosis may clinically benefit from this approach.

This phase II study is designed to compare the efficacy of intra-tumoral gene delivery of CYL-02 plus Gemcitabine treatment or Gemcitabine alone in patient with locally advanced PDAC.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Toulouse
• Collaborators: BIOTHERAPY department of the clinical center of investigation- CIC 1436, Toulouse; InvivoGen Therapeutics
• Treatments: Gemcitabine

Criteria

Inclusion Criteria:

• Histologically or cytologically proven local advanced pancreatic adenocarcinoma patients,

• Non metastatic locally advanced non resectable CP assessed after multidisciplinary staff* and/or surgery,

• Patient without metastasis,

• No previous antitumor treatment or pancreatic resection,

• OMS status ≤ 2,

• Measurable tumor according RECIST criteria v 1.1,

• Patient that give their informed consent,

• Patient older than 18 years of age,

• Patients no contraindication of general anaesthesia,

• Patient with primary pancreatic tumour accessible to EUS (no digestive stenosis or stomach resection).

(*: at least oncologist, radiologist, digestive surgeon and gastroenterologist)

Exclusion Criteria:

• Patients with metastatic pancreatic tumors disease,

• Contraindication of Gemcitabine infusion,

• Non-measurable primary tumour (less than 2 cm in size),

• Borderline tumour according,

• Tumour eligible to a possible neo-adjuvant treatment by radio-chemotherapy or chemotherapy (after multidisciplinary staff*),

• Contraindication to EUS-guided fine needle aspiration biopsy (coagulation disorders),

• Patient in exclusion period or participating in another clinical research protocol,

• Patient that cannot understand or read the information form / consent or is not being able to take the decision to participate to the study,

• Pregnant woman, or of childbearing potential not using contraception,

• Patient under judicial protection, guardianship or curatorship,

• Patient with cystic tumor or pancreatic pseudocyst,

• Patient bearing solid tumors other than adenocarcinoma of the pancreas (endocrine tumor, metastasis),

• Granulocytopenia: granulocytes <1000/mm3,

• Thrombocytopenia: platelet count <100 000/mm3,

• Patient not effectively treated for malignant jaundice (biliary stent or bypass) if present at diagnosis.

(*: at least oncologist, radiologist, digestive surgeon and gastroenterologist)