ToPanc Trial: Survival After Total Versus Partial Pancreaticoduodenectomy for Adenocarcinoma of the Pancreatic Head, Distal Cholangiocarcinoma, and Ampullary Cancer

Not Applicable

Not yet recruiting

• Conditions: Pancreatic Cancer

• Registration Number: NCT06801899
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

The goal of this clinical trial is to learn if total removal of the pancreas is a preferable alternative to partial removal in patients with cancer of the pancreatic head who are at high risk of pancreatic leakage. The main question it aims to answer is:

Does total pancreas removal improve survival without reducing quality of life compared to partial removal?

The only study specific procedures are the collection of 2 blood samples (7.5ml for each time point, preoperatively and during the hospitalisation) and the completion of the questionnaires.

Detailed Description

The pancreas is located in the upper abdomen and has 2 main functions: Production of digestive juices and of insulin, the latter being most important for blood sugar regulation and energy conservation. Certain types of cancer in the pancreatic head are very aggressive, but with complete surgical removal of the tumor and additional chemotherapy cure is possible. For tumor resection, the head of the pancreas as well as duodenum and part of the bile duct are removed. 3 new connections are built: the remaining pancreas, bile duct and stomach are connected to a loop of small intestine.

This operation takes around 6 hours and leads to complications in 20-30% of cases. A serious complication and unfortunately the most frequent is the leaking of the pancreas remnant, with outflow of the aggressive digestive juice into the surrounding tissue. Consequences may be severe bleeding and/or infections. Many studies show that affected patients have an increased risk of tumor recurrence and a reduced survival.

To avoid pancreatic leak, the entire pancreas can be removed. So far, removal of the whole pancreas has only been chosen in cases of very advanced cancer. After both, partial or total pancreas removal, patients need to substitute digestive enzymes. This can be done by capsules, which need to be taken with every meal. But while some patients after partial removal maintain sufficient function to produce insulin, all patients after total removal are diabetic and need insulin injections. In the past, blood sugar control in the absence of insulin production was difficult and accompanied by low quality of life (QoL). This has changed tremendously by the introduction of continuous glucose monitoring (sensors, which are attached to the arm) and automated insulin delivery systems (also known as "artificial pancreas"). This development renders total pancreas removal a reasonable alternative, with the advantage, that only 2 new connections are made: One between the bile duct and small intestine and one between the stomach and the small intestine.

Study question: Is removal of the whole pancreas in patients at high risk of a pancreatic leakage a preferable alternative to partial removal?

For this study, patients with cancer of the pancreatic head who are planned for surgery can be included. These patients will be randomly assigned to two groups:

1. Standard group: partial removal of the pancreas

2. Study group: total removal of the pancreas

Both techniques are safe and are established techniques to treat cancer in the pancreatic head. After the operation, many clinical data will be recorded. The two most important factors will be survival and quality of life, which will be assessed by questionnaires on a regular base. Additionally, postoperative complications, chemotherapy rates, tumor recurrence and many more data will be monitored.

Study Timeline

• Study First Submitted: 2025-01-24
• Study First Submitted QC: 2025-01-29
• Study First Posted: 2025-01-30
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-23
• Study Start: 2025-05
• Primary Completion: 2029-07
• Study Completion: 2029-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

• Adult patients (age ≥ 18 years) scheduled to undergo PD for highly suspected or histologically proven, resectable pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (DCC), and/or ampullary cancer (pancreaticobiliary type)
• Suspected pancreas anastomosis at high-risk for development of a postoperative pancreatic fistula (POPF) (grade "D" according to Schuh et al. (29): Estimation by CT scan, MRI, and/or Endoscopic Ultrasound
• Written informed consent

Exclusion Criteria

• Duodenal carcinoma, ampullary cancer (intestinal type), neuroendocrine tumors, benign tumors, chronic pancreatitis
• Medical conditions that do not allow appreciation of the nature, scope, and possible consequences of the trial as judged by the investigator
• Pregnancy. A beta-Human Chorionic Gonadotropin (bHCG) pregnancy test must to be performed for women of child-bearing potential (defined as premenopausal women who have not undergone surgical sterilization)
• Inability to follow the study procedures, e.g., due to psychological disorders, dementia, etc.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	At 2 years	Number of participants who survived for 2 years after surgery.

Secondary Outcome Measures

Name	Time	Method
Quality of Life (QoL) Diabetes	At 0.5 year, at 1 year, at 2 years	Recorded as participant-reported outcome. Measured by Diabetes Distress Scale (DDS) 17 Questionnaire (only for patients with insulin-dependent diabetes). Scale from 17 to 102, with higher scores indicating a greater level of distress.
Quality of Life (QoL) Pancreatic Cancer	At 0.5 year, at 1 year, at 2 years	Recorded as participant-reported outcome. Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for pancreatic cancer (EORCT QLQPAN26). Scale from 0 to 104, with higher scores indicating a greater level of symptoms or problems.
Postoperative complications (discriminating minor and major complications)	Within 30 day of surgery	Number of participants with postoperative complications. Classified according to the Clavien-Dindo-classification (major complication defined as Clavien-Dindo Grade ≥ III).
Mortality	Within 30 days of surgery	Number of participants who died.
Length of hospital stay in days	Within 30 days of surgery
Re-admission	Within 30 days of surgery	Number of participants who were re-admitted to the hospital.
Re-operation	Within 30 days of surgery	Number of participants who required a re-operation.
Adjuvant Chemotherapy (ACT) completion	At 1 year	Number of days from surgery to ACT completion.
Adjuvant Chemotherapy (ACT) initiation	At 1 year	Number of days from surgery to ACT initiation.
Disease-Free Survival (DFS)	At follow-up, up to 4.5 years	Number of participants who remained free of disease. Defined as no new metastasis or local recurrence on CT or MRI imaging, and, if applicable, laboratory tests (new Ca19-9 increase).
Functional status	At 0.5 year, at 1 year, at 2 years	Recorded as participant-reported outcome. Measured by Eastern Cooperative Oncology Group (ECOG) Performance Status Scale. Scale from 1 to 5, with higher scores indicating a greater level of disability.
Body Mass Index (BMI)	At 0.5 year, at 1 year, at 2 years

Trial Locations

Locations (1)

Inselspital, Bern University Hospital; 🇨🇭 Bern, Switzerland