Pancreatic Head Resection or Total Pancreatectomy With Islet Autotransplantation in Patients With Periampullary Cancer and High Risk Profile for the Development of Postoperative Pancreatic Fistula

Study Overview
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Brief Summary
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The primary objective of this clinical trial is to evaluate whether primary total pancreatectomy with simultaneous islet autotransplantation compared with pancreatic head resection (alone) can reduce perioperative morbidity and time to initiation of adjuvant therapy in patients with a high-risk constellation for pancreatic fistulas.

Official Title
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Pancreatic Head Resection or Total Pancreatectomy With Islet Autotransplantation (IAtx) in Patients With Periampullary Cancer and High Risk Profile for the Development of Postoperative Pancreatic Fistula (POPF)

Conditions
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Periampullary Cancer, Postoperative Pancreatic Fistula

Intervention / Treatment
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* Biological: Intraportal transplantation of isolated autologous pancreatic islets after total pancreatectomy
* Procedure: Pancreaticoduodenectomy (classic Whipple or pylorus-preserving)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: suspected or confirmed periampullary carcinoma (tumor) and indication for PPPD (pylorus-preserving pancreaticoduodenectomy) or Whipple surgery high-risk profile for the development of a postoperative pancreatic fistula (POPF) after pancreatic head resection: soft pancreas and Pancreatic duct diameter < 3 mm (preoperative and intraoperative confirmation) written informed consent of the participant after successful Informed consent Exclusion Criteria: patients on whom another procedure is to be performed simultaneously in addition to PPPD or Whipple surgery confirmed other primary tumor previous transplantation of an organ or tissue known infection with HIV (HIV antibodies) positive hepatitis C antibodies, positive hepatitis B surface antigens and hepatitis Bc antibodies insulin-treated diabetes mellitus history of hypersensitivity to any of the drugs used or their ingredients or to drugs with a similar chemical structure concurrent participation in another clinical trial (incl. within the last 4 weeks prior to inclusion). addiction or other medical conditions that do not allow the subject to understand the nature and not be able to appreciate the nature, scope and possible consequences of the trial pregnant or breastfeeding women women of childbearing age, except for women who meet the following criteria: Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml) Post-operative (6 weeks after bilateral ovariectomy with or without hysterectomy) Regular and correct use of a contraceptive method with an failure rate < 1% per year Sexual abstinence Vasectomy of the partner evidence that the patient is unlikely to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Therapy<br>Total pancreatectomy with autologous islet cell transplantation | Biological: Intraportal transplantation of isolated autologous pancreatic islets after total pancreatectomy<br>* Islet cells are isolated from patients healthy pancreatic tissue. Following total pancreatectomy, these autologous cells are injected into the portal vein, to implant in the liver and produce insulin.<br>|
| Other: Standard Therapy<br>Pancreaticoduodenectomy (classic Whipple or pylorus-preserving) | Procedure: Pancreaticoduodenectomy (classic Whipple or pylorus-preserving)<br>* As a standard procedure, the tumor-affected region of the pancreatic head with surrounding tissue and lymph nodes is removed during surgery. Reconstruction is performed by pancreaticojejunostomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration between surgery and time fit for adjuvant treatment (postoperative day X) | Time (days) between surgery and the date of certified fitness to begin adjuvant therapy, confirmed by an oncology consult, starting at day of discharge, than assessed at POD 90, POD 180, POD 365, 24 months | From day of discharge until confirmed fitness for adjuvant treatment or 24 months, whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of actual start of adjuvant therapy in both arms | Postoperative day on which adjuvant therapy was started | From POD 90 until actual start of therapy or 24 months whichever came first | 
| Rate of peri-operative morbidity/mortality acc. to Clavien-Dindo classification | Rate of peri-operative morbidity/mortality will be assessed acc. to Clavien-Dindo classification | After enrolment of the patient until 24 months after intervention | 
| Rate of (serious) adverse events | Rate of (serious) adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0, 2017) | After randomization of the patient until 24 months after intervention | 
| Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire | The QoL analyses will include QoL mean values, QoL response. EORTC QLQ C30 contains 30 questions28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much). 2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent).; assessed at POD 90, POD 180, POD 365, and 24 months after surgery | From date of screening until 24 months after intervention | 
| Patient reported outcomes: Quality of life EORTC PAN26 questionnaire | The QoL analyses will include QoL mean values, QoL response. EORTC QLQ PAN26 contains 30 questions regarding pain, nutrition, body fitness, sexuality, from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much). 28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much); , assessed at POD 90, POD 180, POD 365, and 24 months after surgery 2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent). | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: continuous glucose monitoring (CGM) | Metabolic outcome will be determined on continuous monitoring of glucose (CGM) in plasma (mmol/L) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: glucagon | Metabolic outcome will be determined on the hormone glucagon in plasma at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: glycohemoglobin HbA1c | Metabolic outcome will be determined on glycohemoglobin (HbA1c in %) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: C-peptide | Metabolic outcome will be determined on serum C-peptide (nmol/L) as measure for functionality of pancreas at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: fructosamine | Metabolic outcome will be determined on serum fructosamine (µmol/L) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: insulin requirement | Metabolic outcome will be determined on requirement of insulin (yes/no) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: number of hypoglycemic events | Metabolic outcome will be determined on number of hypoglycemic events (defined as value of blood glucose below 3.5 mmol/l) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of metabolic outcome in both arms: severity of hypoglycemia | Metabolic outcome will be determined on severity of hypoglycemic events (decrease of blood glucose level) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention | From date of screening until 24 months after intervention | 
| Comparison of long-term oncological course (24 months) in both arms: tumor markers | Within 24 months after intervention, oncological outcome is evaluated, as measured by tumor markers CA 19-9, CEA | 24 months after intervention | 
| Comparison of long-term oncological course (24 months) in both arms: recurrence | Within 24 months after intervention, oncological outcome is evaluated, as measured by recurrences of tumor shown in CT imaging | 24 months after intervention | 
| Comparison of long-term oncological course (24 months) in both arms: occurence of metastases | Within 24 months after intervention, oncological outcome is evaluated, as measured by metastases shown in CT imaging | 24 months after intervention |