Periampullary Cancer, Postoperative Pancreatic Fistula
Conditions
Brief summary
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.
Interventions
BIOLOGICALIntraportal transplantation of isolated autologous pancreatic islets after total pancreatectomy
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.
PROCEDUREPancreaticoduodenectomy (classic Whipple or pylorus-preserving)
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.
Sponsors
Technische Universität Dresden
German Cancer Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH \> 40 U/ml) 2. Post-operative (6 weeks after bilateral ovariectomy with or without hysterectomy) 3. Regular and correct use of a contraceptive method with an failure rate \< 1% per year 4. Sexual abstinence 5. Vasectomy of the partner * evidence that the patient is unlikely to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration between surgery and time "fit for adjuvant treatment" (postoperative day X) | From day of discharge until confirmed fitness for adjuvant treatment or 24 months, whichever came first | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of actual start of adjuvant therapy in both arms | From POD 90 until actual start of therapy or 24 months whichever came first | Postoperative day on which adjuvant therapy was started |
| Rate of peri-operative morbidity/mortality acc. to Clavien-Dindo classification | After enrolment of the patient until 24 months after intervention | Rate of peri-operative morbidity/mortality will be assessed acc. to Clavien-Dindo classification |
| Rate of (serious) adverse events | After randomization of the patient until 24 months after intervention | Rate of (serious) adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0, 2017) |
| Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire | From date of screening until 24 months after intervention | 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 |
| Patient reported outcomes: Quality of life EORTC PAN26 questionnaire | From date of screening until 24 months after intervention | 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). |
| Comparison of metabolic outcome in both arms: continuous glucose monitoring (CGM) | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: glucagon | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: glycohemoglobin HbA1c | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: C-peptide | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: fructosamine | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: insulin requirement | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: number of hypoglycemic events | From date of screening until 24 months after intervention | 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 |
| Comparison of metabolic outcome in both arms: severity of hypoglycemia | From date of screening until 24 months after intervention | 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 |
| Comparison of long-term oncological course (24 months) in both arms: tumor markers | 24 months after intervention | Within 24 months after intervention, oncological outcome is evaluated, as measured by tumor markers CA 19-9, CEA |
| Comparison of long-term oncological course (24 months) in both arms: recurrence | 24 months after intervention | Within 24 months after intervention, oncological outcome is evaluated, as measured by recurrences of tumor shown in CT imaging |
| Comparison of long-term oncological course (24 months) in both arms: occurence of metastases | 24 months after intervention | Within 24 months after intervention, oncological outcome is evaluated, as measured by metastases shown in CT imaging |
Countries
Germany
Contacts
CONTACTBarbara Ludwig, Prof. Dr.
PRINCIPAL_INVESTIGATORBarbara Ludwig, Prof. Dr.
Department of internal Medicine III
PRINCIPAL_INVESTIGATORMarius Distler, Prof. Dr.
Department of Visceral, Thoracic and Vascular Surgery
Outcome results
None listed