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

NCT02806687 | Completed Phase 2 DMC

• 2 other identifiers: RC31/13/70462016-000572-20
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Pancreatic Adenocarcinoma

Keywords

Locally advanced pancreatic adenocarcinoma; gene therapy; gemcitabine; chemosensitization

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression free-survival (PFS) is defined as the time interval between the date of the beginning of the treatment (Arm A: first injection of CYL-02; Arm B: first injection of Gemcitabine) and the date of local or regional progression or metastases progression or occurrence of distant metastases (including liver or non-liver metastases) or occurrence of 2nd pancreatic cancer or death (all causes), whichever occurs first. Patients alive and free of all these events will be censored at the last follow-up. Other events will be ignored (EJC 2014 Bonnetain et al).

  From date to randomization until the date of first documented progression or date of death, whichever came first, assessed up to 12 months.

Secondary Outcomes (7)

• Overall survival

  Up to 1 year

• Tumor response

  Difference between baseline and months 1, 2, 4, 6 and 12 months.

• Quality of life change

  Difference between baseline and month 12.

• Biological tumoral marker

  Difference between baseline and month 12

• Incidence of treatment-emergent adverse events

  Up to 12 months

Study Arms (2)

Gene Therapy product CYL-02

EXPERIMENTAL

Two EUS-guided intratumor injections of CYL-02 at one month interval plus Gemcitabine (3 weeks/month) during two months followed by four months Gemcitabine alone (3 weeks/month) or until progression.

Drug: Gene Therapy product CYL-02; Drug: Gemcitabine

Standard of care

ACTIVE COMPARATOR

Gemcitabine alone 3 weeks/month during 6 months (or until progression).

Drug: Gemcitabine

Interventions

Gene Therapy product CYL-02 DRUG

Gene Therapy product CYL 02 = = plasmid DNA encoding SST2 + DCK::UMK genes pre-complexed to linear polyethylenimine. 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 intratumoral injection of CYL-02 is followed by three IV infusions of Gemcitabine (1000 mg/m2) at 48 hours and then every week. 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. Patients have infusion of Gemcitabine 3 weeks/month during 6 months (or until progression).

Also known as: CYL-02

Gene Therapy product CYL-02

Gemcitabine DRUG

Gemcitabine alone 3 weeks/month during 6 months (or until progression).

Gene Therapy product CYL-02; Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 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)

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• BIOTHERAPY department of the clinical center of investigation- CIC 1436, Toulouse: collaborator
• InvivoGen Therapeutics: collaborator

Study Sites (7)

APHP Hôpital Beaujon

Clichy, 32110, France

Location

Hôpital privé Jean Mermoz

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

CHU de Marseille Hôpital Nord

Marseille, 13015, France

Location

Institut régional du Cancer

Montpellier, 34298, France

Location

Rangueil Hospital

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Interventions

Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Louis Buscail, MD PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2016
• First Posted: June 21, 2016
• Study Start: January 30, 2017
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)