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

Official title

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)

Overview

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

• Biological Intraportal 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.
• Procedure Pancreaticoduodenectomy (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.

Primary outcome measures

• Duration between surgery and time "fit for adjuvant treatment" (postoperative day X) [Time frame: From day of discharge until confirmed fitness for adjuvant treatment or 24 months, whichever came first]

Secondary outcome measures (12)

• Comparison of actual start of adjuvant therapy in both arms [Time frame: 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 [Time frame: After enrolment of the patient until 24 months after intervention]
• Rate of (serious) adverse events [Time frame: After randomization of the patient until 24 months after intervention]
• Patient reported outcomes: Quality of life EORTC QLQ C30 questionnaire [Time frame: From date of screening until 24 months after intervention]
• Patient reported outcomes: Quality of life EORTC PAN26 questionnaire [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: continuous glucose monitoring (CGM) [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: glucagon [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: glycohemoglobin HbA1c [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: C-peptide [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: fructosamine [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: insulin requirement [Time frame: From date of screening until 24 months after intervention]
• Comparison of metabolic outcome in both arms: number of hypoglycemic events [Time frame: From date of screening until 24 months after intervention]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 1 center

• University Hospital Carl Gustav Carus Technische Universität Dresden — Dresden

Publications

• Hempel S, Kolbinger FR, Oehme F, Radulova-Mauersberger O, Schmid J, Schubert U, Schepp F, Bornstein S, Korn S, Trips E, Weitz J, Distler M, Ludwig B. Pancreatoduodenectomy versus total pancreatectomy and simultaneous intraportal islet autotransplantation for periampullary cancer at high-risk of postoperative pancreatic fistula (XANDTX-trial): Protocol of a randomized controlled pilot trial. PLoS O PMID 40720532

Identifiers

NCT: NCT05843877 · TUD-XandTX-079 · 2023-507773-17-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗