Efficacy and Safety of TPIAT for Resectable Adenocarcinoma of the Pancreas Region at High Risk of Postoperative Fistula

NCT05116072 | Recruiting Phase 1 DMC

• 2 other identifiers: 2019_272021-A00136-35
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Curative management of locally resectable invasive adenocarcinomas located in the cephalic region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major surgery that often leads to major complications including approximately 20% of relevant clinical postoperative pancreatic fistula. Postoperative complications following pancreaticoduodenectomy can lead to early discontinuation of the complete oncologic strategy, i.e., chemotherapy for malignancy is performed in only about a third of patients who experienced a grade C fistula. A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that involves the complete and definitive resection of all pancreatic tissue, eliminating any risk of postoperative pancreatic fistula but is associated with unavoidable endocrine insufficiency and potentially severe metabolic complications, such as "brittle diabetes". Total Pancreatectomy following by intraportal Islet AutoTransplantation (TPIAT) can prevent "brittle diabetes" and improve the quality of life. The endocrine islets can be isolated from the pancreatic surgical specimen with standardized procedures and transplanted in the liver through intraportal infusion, in absence of immunosuppression and allow adequate control of glucose metabolism with a reduced need for exogenous insulin and an effective graft function in 70% of cases at 3 years Thereby, the investigators hypothesize that total pancreatectomy with intraportal Islet autotransplantation rather than classical pancreaticuduodenectomy, in patients with high-risk of postoperative fistula will increase the rate of complete access to adjuvant chemotherapy, while maintaining an adequate metabolic control.

Conditions

Adenocarcinoma of the Pancreas; Adenocarcinoma of the Duodenum; Ampullary Adenocarcinoma

Keywords

the cephalic region of the pancreas; total pancreatectomy; postoperative pancreatic fistula; islet transplantation; adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• the rate of patients who have completed the chemotherapy planned

  success is defined when patients treated with TPIAT will have completed the adjuvant systemic chemotherapy initially approved and planned by the local multidisciplinary expert team according to current international guidelines

  at postoperative month 12 following surgery.

Secondary Outcomes (12)

• Rate of postoperative complications related to total pancreatectomy.

  At 3 months following surgery.

• Rate of complications related to islet transplantation during the study

  through study completion, at 36 months following surgery.

• Mean time (in weeks) between TPIAT and adjuvant systemic chemotherapy.

  through study completion, at 36 months following surgery.

• Rate of patients with cancer recurrence

  at 3, 6, 9, 12, 24, and 36 months following surgery.

• Postoperative diabetes and pancreatic endocrine insufficiency following pancreatic surgery as recommended by the best standard care will be evaluated

  functions before surgery and at day 7 and at 3, 12, 24 and 36 months following surgery.

Study Arms (1)

Experimental group

EXPERIMENTAL

Patients benefited from total pancreatectomy for resectable adenocarcinoma of the cephalic region at high risk of postoperative pancreatic fistula, with intaportal/intramuscular islet autotransplantation

Procedure: total pancreatectomy; Biological: intraportal islet autotransplantation

Interventions

total pancreatectomy PROCEDURE

The total pancreatectomy will be performed in two steps: The pancreatectomy will begin by a standard pancreaticoduodenectomy procedure. The section margin will be sent for intraoperative histological analysis to confirm the absence of invasion of the left remnant pancreas. When absence of tumor invasion is confirmed and the high-risk of postoperative pancreatic fistula is validated intraoperatively, the extended left distal pancreatectomy will be performed, with splenic preservation when possible. Then, the left side of the pancreas will be resected and cooled (4-6°) in the preservation solution and shipped to Lille Biotherapy platform to perform islet isolation and purification. The reconstruction after total pancreatectomy will be done as usually performed by center expert surgeon.

Experimental group

intraportal islet autotransplantation BIOLOGICAL

The final islet preparation will be cultured and shipped 48 hours after total pancreatectomy from the Lille laboratory to the surgical center, and finally transplanted into the patient through a venous catheter placed in the portal trunk (91% of the total islet mass) and at the same time, a small fraction of the isolated islet (5% of the total islet mass) will be transplanted into the forearm muscle.

Experimental group

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Locale resectable invasive adenocarcinomas located in the cephalic region of the pancreas documented by endoscopic ultrasonography with fine-needle aspiration biopsy
• pancreatic adenocarcinoma;
• duodenal adenocarcinoma;
• ampullary adenocarcinoma;
• and IPMNs with adenocarcinoma degeneration;
• A potentially curative strategy with primary tumor resection approved by a multidisciplinary expert team
• A high-risk of CR-POPF
• Women of childbearing potential should only be included after a confirmed menstrual period, and a negative highly sensitive urine or serum pregnancy test and must agree to be subjected to a monthly pregnancy test (urine or blood) until the end of the relevant systemic exposure to chemotherapy agents, in accordance with current CTFG recommendations (Recommendations related to contraception and pregnancy testing in clinical trials);
• Women of child-bearing potential and male subjects must agree to use a birth control methods which may be considered as highly effective (failure rate of less than 1% per year ) as recommended by the CTFG (Cinical Trials Facilitation and Coordination Group, version 1.1). These recommandations related to contraception and pregnancy testing in clinical trials suggested such method (see below) that will be use during chemotherapy exposure for included women of child-bearing potential and woman of child-bearing potential when partner of included male : combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal) ; progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) ; intrauterine device (IUD) ; intrauterine hormone-releasing system ( IUS) ; bilateral tubal occlusion; vasectomised partner ;sexual abstinence For included male partner of a women of child-bearing potential, contraception with condom.
• Contraception will be perform during the relevant systemic exposure to chemotherapy agents and will be extended by 6 months for women of childbearing potential and by 1 month for men included as recommended by the CTFG
• Patient covered by a health insurance system
• Patient who provides a written informed consent to participate to the study

You may not qualify if:

• Patient will be screened and excluded if they present a preoperative diabetes defined by a stimulated C-peptide \< 0.5 ng/mL relative to blood glucose \> 2 g/dL, at 2 hours in post prandial
• Patients with a known or highly suspected genetic syndrome associated with a risk of pancreatic adenocarcinoma: familial pancreatic cancer, multiple familial melanoma, Peutz-Jeghers syndrome, hereditary chronic pancreatitis, cystic fibrosis, familial breast Ovarian Cancer, Lynch syndrome, adenomatous polyposis family, Li Fraumeni syndrome, Multi-endocrine disorder type I;
• Multifocal pancreatic adenocarcinomas identified during preoperative evaluation;
• Performance status and comorbidity profile inappropriate for a major abdominal surgery;
• Contraindication for autologous islet intraportal transplantation
• Current or indicated/scheduled neoadjuvant chemotherapy;
• Extra pancreatic metastasis identified during preoperative evaluation (high-definition cross-sectional imaging with thorax-abdomen-pelvis multi-detection computed tomography or abdominal MRI with T1, T2 and diffusion weighted sequences) or during intraoperative assessment (clinical examination and ultrasonography);
• Need for complex vascular reconstructions (endovascular treatment or release of the arcuate ligament will be not considered as complex vascular reconstructions), major vein reconstructions will exclude the patients because of the over-risk of portal thrombosis following islet intraportal infusion.
• evident macroscopically or biologically proved post biliary drainage pancreatitis that jeopardize islet isolation
• Known infection or positive serology performed at screening for human immunodeficiency virus (HIV) infection, Hepatitis B or C virus infection, HTLV infection or syphilis infection.
• Active infection for SARS-CoV-2 virus (positive PCR), which will require rescheduling of the intervention 30 days later.
• Pregnant or breastfeeding woman
• Dihydropyrimidine dehydrogenase total deficiency
• Ethics / regulatory criteria :
• Person unable to understand purposes, benefits and risks of the study and/or unable to provide a written informed consent.

Sponsors & Collaborators

• University Hospital, Lille: lead
• Ministry of Health, France: collaborator

Study Sites (1)

Hop Claude Huriez Chu Lille

Lille, 59037, France

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• François PATTOU, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

François PATTOU, MD,PhD

CONTACT

0320445962; fpattou@univ-lille.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: November 10, 2021
• Study Start: February 20, 2022
• Primary Completion (Estimated): February 20, 2028
• Study Completion (Estimated): February 20, 2030
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

FR (1)