Non-metastasized, adenocarcinoma of the pancreatic head/uncinate process or body of pancreas that was treated with extended pancreatic head/body resection larger than 2 cm in size (=cT2) and/or in close contact with the mesenterico-portal axis and SMA (less than 3 mm). MedDRA version: 18.1 Level: LLT Classification code 10033602 Term: Pancreatic adenocarcinoma resectable System Organ Class: 100000004864
Conditions
Interventions
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Gemcitabin
Other descriptive name: GEMCITABINE (AS HYDROCHLORIDE)
Concentration unit: mg milligram(s)
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Resectable adenocarcinoma of the pancreatic head/uncinate process or body of pancreas that was treated with extended pancreatic head/body resection with a tumor size greater 2 cm (=cT2) and/or close contact to the superior mesenteric vessels (=3 mm in preoperative staging). - Histology/cytology prove OR patients with CT graphical high-grade suspected adenocarcinoma of the pancreas, CA19-9 >100 U/ml, hyperbilirubinemia, B-symptoms and interdisciplinary decision for therapy - No evidence of metastasis to distant organs (liver, peritoneum, lung, others). - For determination of resectability, a multi-detector CT (MDCT) with at least 16 rows applying both oral and intravenous contrast media is performed. MDCT-based imaging focuses on the upper abdomen with native, arterial, and parenchyma phase, where the parenchyma phase should include the pelvis. Imaging criteria derived from the recent consensus definition of the Society of Surgical Oncology, the American Society of Clinical Oncology and the American Hepato-Pancreatico-Biliary Association are applied for preoperative assessment of local resectability. - Potential Resectability: visualizable fat plane around celiac and superior mesenteric arteries, and patent superior mesenteric/portal vein (SMV/PV). - Borderline Resectability: substantial superior mesenteric/portal vein impingement, tumor abutment on the SMA 10.0 mg/dl undergo preoperative biliary decompression, preferentially by interventional endoscopy) - White blood cell count = 3.5 x 109/ml, platelet count = 100 x 109/ml - Ability to understand and willingness to consent to formal requirements for study participation - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 137 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 273
Exclusion criteria
Exclusion criteria: - Age = 18 years - Neuroendocrine, acinar cancer - Cancers of the pancreatic body or tail (lesions left to the SMV) that were treatd with distal pancreatectomy - Recurrent disease - Infiltration of extrapancreatic organs (except duodenum and transverse colon) - Persistent cholestasis/cholangitis despite adequate biliary stenting -Gastric outlet obstruction, especially in the event of endoscopically evidenced tumor invasion into the gastroduodenal mucosa. - Tumor specific pre-treatment - History of gastrointestinal perforation, e.g. perforated colonic diverticulitis, abdominal abscess or intestinal fistula within 6 months prior to potential study participation - Radiographic evidence of severe portal hypertension/cavernomatous transformation that may, at the discretion of the participating investigators, hamper surgery - Other concurrent malignancies except for basal cell cancer of the skin and in-situ cervical cancer - Premalignant hematologic disorders, e.g. myelodysplastic syndrome - Severe organ dysfunctions (e.g. Liver cirrhosis = Child B; Cardio-pulmonal diseases (NYHA =III, arrhythmia Lown III/IV, global respiratory insufficiency); Ascites; Acute pancreatitis; bleeding diathesis, coagulopathy, need for full-dose anticoagulation or INR > 1.5; other severe diseases that might prevent completion of the treatment regimen) - Chronic infectious diseases, especially immune deficiency syndromes, e.g. HIV infection, active tuberculosis within 12 months prior to potential study participation - History of severe neurologic disorders, e.g. cerebrovascular ischemia - History of prior deep venous thrombosis or pulmonary embolism - Pregnant or nursing women are ineligible and patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial and for 6 months following the trial - Serious medical, psychological, familial, sociological or geographical conditions or circumstances potentially hampering compliance with the study protocol and follow-up - Participation in other clinical trials during the last 6 months before allocation to trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy of neoadjuvant RCTx in improving 3-year survival probability from 30% in the control arm undergoing upfront surgery without neoadjuvant RCTx to 42% (relative increase of 40%) in the study arm undergoing RCTx. The underlying guess of a 30% 3-year survival probability in the control group derives from an assumed median overall survival (MOS) of 20.7 months which corresponds with a MOS of 17.9 months to 23.6 months reported in several randomized trials.;Secondary Objective: - Histology-proven R0 resection rate based on a standardized histopathological handling of the surgical specimen. - Frequency of moderate and severe toxicity events and drop-out rate due to therapy related toxicity (NCI Common Toxicity Criteria v2.0) - Resectability rate (Note: includes both R0 and R1 resection status) - Rate of unexpected intraoperative irregularities, operative time, blood transfusion requirement, postoperative morbidity rate, especially that of pancreatic fistula, and mortality rate - Rate of patients with severe postoperative complications (postop. recovery > 8 weeks) rendering adjuvant treatment worthless - Disease progression during neoadjuvant therapy - Quality of life analysis (EORTC QLQ C30 questionnaire) - Median disease-free survival (DFS, local and distant), overall survival (OS) - First site of tumor recurrence - Utility of 18F-FDG-PET/CT in refining preoperative staging accuracy and determining response to preoperative therapy;Primary end point(s): Survival time;Timepoint(s) of evaluation of this end point: From the date of randomization to death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Histology-proven R0 resection rate based on a standardized histopathological handling of the surgical specimen. - Frequency of moderate and severe toxicity events and drop-out rate due to therapy related toxicity (NCI Common Toxicity Criteria v2.0) - Resectability rate (Note: includes both R0 and R1 resection status) - Rate of unexpected intraoperative irregularities, operative time, blood transfusion requirement, postoperative morbidity rate, especially that of pancreatic fistula, and mortality rate - Rate of patients with severe postoperative complications (postop. recovery > 8 weeks) rendering adjuvant treatment worthless - Disease progression during neoadjuvant therapy - Quality of life analysis (EORTC QLQ C30 questionnaire) - Median disease-free survival (DFS, local and distant), overall survival (OS) - First site of tumor recurrence - Utility of 18F-FDG-PET/CT in refining preoperative staging accuracy and determining response to preoperative therapy;Timepoint(s) of evaluation of this end point: At end of trial | — |
Countries
Germany
Contacts
Public ContactStudy Coordination
University Medical Center Hamburg-Eppendorf, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie
Outcome results
None listed