Efficacy and Safety of TPIAT for Resectable Adenocarcinoma of the Pancreas Region at High Risk of Postoperative Fistula
- Conditions
- Ampullary AdenocarcinomaAdenocarcinoma of the PancreasAdenocarcinoma of the Duodenum
- Interventions
- Procedure: total pancreatectomyBiological: intraportal islet autotransplantation
- Registration Number
- NCT05116072
- Lead Sponsor
- University Hospital, Lille
- 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.
- Detailed Description
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. Severe postoperative pancreatic fistulas (grade C) require reoperation or lead to organ failure and/or mortality. In an extensive international registry study of pancreaticoduodenectomy procedures, chemotherapy for malignancy was performed in only about 33% (on time in 7% and delayed in 25.6 % of patients) and never delivered in about 67,4 % of patients who experienced a grade C fistula. Therefore, postoperative complications following pancreaticoduodenectomy can lead to early discontinuation of the complete oncologic strategy.
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.
Total pancreatectomy could represent a major shift in the surgical management of patients with a high-risk of postoperative fistula by eliminating the life-threatening risk associated with fistula and by increasing the opportunity to initiate and to complete adjuvant chemotherapy without delay.
However, total pancreatectomy is associated with unavoidable endocrine insufficiency and potentially severe metabolic complications, such as "brittle diabetes".
Total Pancreatectomy with intraportal Islet AutoTransplantation (TPIAT) is currently performed in patients with chronic pancreatitis under chronic pain failing endoscopic treatment and dependent on long-term opioid treatment.
Therefore, islet autotransplantation following total pancreatectomy 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental group total pancreatectomy Patients benefited from total pancreatectomy for resectable adenocarcinoma of the cephalic region at high risk of postoperative pancreatic fistula, with intaportal/intramuscular islet autotransplantation Experimental group intraportal islet autotransplantation Patients benefited from total pancreatectomy for resectable adenocarcinoma of the cephalic region at high risk of postoperative pancreatic fistula, with intaportal/intramuscular islet autotransplantation
- Primary Outcome Measures
Name Time Method the rate of patients who have completed the chemotherapy planned at postoperative month 12 following surgery. 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
- Secondary Outcome Measures
Name Time Method Rate of postoperative complications related to total pancreatectomy. At 3 months following surgery. postoperative complication will be evaluated with Dindo Clavien classification
Mean time (in weeks) between TPIAT and adjuvant systemic chemotherapy. through study completion, at 36 months following surgery. the time in weeks between TPIAT procedure and the adjuvant systemic chemotherapy will be reported
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. Postopeartive diabetes and exocrine insufficiency will be evaluated with clinical examination (symptoms, Pancreatic enzyme replacement therapy dosage, Diabetes medication : non insulin medication, insulin (daily insuline dosage UI/kg); blood samples (Fasting C-peptide and glycemia, Post-prandial C-peptide and glycemia, HbA1C (%))
Mortality rate at day 7 and at 3, 12, 24 and 36 months following surgery. patient's death will be reported
islet transplantation success rate defined by CIT criteria at 3, 12, 24 and 36 months following surgery. Islet transplantation succes status is defined by HbA1C \< 7% AND no severe hypoglycemic event
islet transplantation success rate defined by IGLS 2.0 criteria at 3, 12, 24 and 36 months following surgery. Islet transplantation succes status is defined by HbA1C \< 7% AND no severe hypoglycemic event AND C-peptide ≥ 0.2 ng/mL
Rate of patients with cancer recurrence at 3, 6, 9, 12, 24, and 36 months following surgery. The cancer recurrence will be assessed according standard of care imaging (Thorax multi-detection Computed Tomography, Abdomino-pelvis imaging : Mutli-detection Computed Tomography OR Magnetic Resonance Imaging) through the follow up using the Recist 1.1 criteria
Rate of complications related to islet transplantation during the study through study completion, at 36 months following surgery. complications related to islet transplantation will be reported according to CTCAE v5.0.
EORTC QLQ-C30 core with it specific pancreatic module QLQ -PAN26 at 3, 12, 24 and 36 months following surgery. EORTC QLQ-C30 and QLQ -PAN26 are self-completion questionnaires specific to cancer patients quality of life and pancreatic cancer patients quality of life
Rate of adverse events through study completion, at 36 months following surgery. adverse events will be reported according to CTCAE v5.0 and classified according to their suspected or confirmed reason (i.e. chemotherapy, intraportal islet transplantation, pancreatic surgery)
Primary islet Graft Function at 1 month following TPIAT. Defined by the Beta 2 score calculated at 1 month post TPIAT using blood sample with fasting C peptide and glycemic, HbA1c and exogenous insuline requirement
mean number of Serious Hypoglycemic Event (SHE) since last visit at day 7 and months 3, 12, 24 and 36 following surgery. Serious Hypoglycemic Event is defined as one requiring third-party assistance or resulting in hospitalization in an intensive care unit
Trial Locations
- Locations (1)
Hop Claude Huriez Chu Lille
🇫🇷Lille, France