Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer
- Conditions
- Colorectal Liver Metastasis
- Interventions
- Procedure: Resection of colorectal liver metastases
- Registration Number
- NCT04678583
- Lead Sponsor
- Technische Universität Dresden
- Brief Summary
the ARMANI trial will test the hypothesis, if an anatomic resection (AR) improves long-term outcome vs. a non-anatomical resection (NAR) in patients undergoing surgery for RAS-mutated colorectal liver metastasis (CRLM).
- Detailed Description
Despite increasing application and success of personalized treatment in medical oncology, little progress has been made in personalized surgical cancer therapy. The ARMANI trial presents the first prospective, randomized trial to evaluate effectiveness and safety of molecular-guided resection in patients with colorectal liver metastasis (CRLM). While CRLM might be removed independently of the liver's segmental borders, retrospective data favor anatomic resections in the subgroup of patients with a mutation in the RAS oncogene. Therefore, the ARMANI trial will test the hypothesis, if an anatomic resection (AR) improves long-term outcome vs. a non-anatomical resection (NAR) in patients undergoing surgery for RAS-mutated CRLM. The trial will be carried out among 11 high-volume centers of hepato-biliary surgery in Germany. A total of 220 patients will be enrolled and randomized in a 1:1 ratio to undergo an AR vs. NAR. The primary endpoint is intrahepatic disease-free survival (iDFS). In addition, the study will provide important data on perioperative outcomes and quality of life for both surgical techniques. Given the trend among liver surgeons to aim for parenchymal-sparing operations to preserve liver parenchyma, a positive trial will be practice changing and present the first piece of high-level evidence on benefits of personalized surgical therapy guided by the tumor's mutational profile in patients with CRLM.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
- Colorectal cancer with RAS mutation (KRAS or NRAS)
- Colorectal liver metastases (single or multiple)
- Planned R0 resection of liver metastases (and primary tumor, if present)
- Anatomical and non-anatomical liver resection technically feasible
- Male and female patients, age ≥ 18 years
- Written informed consent
- Extrahepatic metastases
- Planned staged liver resection (e.g. two-stage hepatectomy)
- Diagnosis of another cancer < 5 years prior to randomization Exceptions: curatively treated in situ cervical cancer, curatively resected non-melanoma skin cancer
- Expected lack of compliance
- Addiction or other illnesses which do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A - Anatomical resection Resection of colorectal liver metastases removal of the entire, tumor-bearing liver segment(s) B - Non-anatomical resection Resection of colorectal liver metastases metastasectomy with a margin of healthy liver tissue irrespective of segmental borders
- Primary Outcome Measures
Name Time Method Intrahepatic disease-free survival (iDFS) 24 months Time from operation date to date of disease recurrence in the liver, followed up at intervals of three months for a maximum duration of 24 months or until death. Any new, solid lesion in the liver after resection of all CRLM that fulfils imaging criteria (CT, MRI) of a metastasis is counted as an iDFS event.
- Secondary Outcome Measures
Name Time Method Assessment of additional oncological and perioperative outcomes: Transfusion of blood, transfused packed red blood cells (PRBC), fresh frozen plasma (FFP) and / or platelet concentrate (PC) [units] 48 hours after surgery Administration of blood transfusions is documented for the intra- and postoperative period within 48 hours postoperatively.
Assessment of additional oncological and perioperative outcomes: Duration of postoperative hospital stay [days] At day of discharge, assessed up to 90 days Postoperative day 1 until day of discharge
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Platelet count pre-operatively, 5 days after surgery Platelet count will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Albumin pre-operatively, 5 days after surgery Levels of albumin will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Duration of postoperative intermediate/intensive care unit stay [days] At day of discharge, assessed up to 90 days Days on the intermediate care unit (IMC) or intensive care unit (ICU) after surgery. Patient's stay in the recovery room exceeding 24 hours is counted as ICU stay
Assessment of additional oncological and perioperative outcomes: 90-day mortality 90 days after surgery Death due to any cause within 90 days after surgery
Assessment of additional oncological and perioperative outcomes: Kind of peri-operative morbidity after resection 90 days after surgery Kind of peri-operative complications after resection of the primary tumor
Assessment of additional oncological and perioperative outcomes: Intraoperative blood loss [mL] During surgery Intraoperative blood loss presents the amount of blood lost from skin incision until skin closure. Spilling water and ascites will be subtracted. Swabs will be squeezed and their content will also be sucked and added to the fluid collected in the suction containers.
Assessment of additional oncological and perioperative outcomes: Operating time [min] During surgery Time from skin incision until placement of last skin staple/suture.
Assessment of additional oncological and perioperative outcomes: Frequency of peri-operative morbidity after resection 90 days after surgery Frequency of peri-operative complications after resection of the primary tumor
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: aspartate-aminotransferase pre-operatively, 5 days after surgery Levels of aspartate-aminotransferase (AST) will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Frequency invasive re-interventions 30 days after surgery Invasive re-interventions such as placement of interventional drains, Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement, chest tube placement, and re-laparotomy within 30 days after the index operation or during patients' initial hospital stay
Assessment of additional oncological and perioperative outcomes: Frequency of Overall survival (OS) 24 month The overall survival of all patients is assessed between operation date to date of death of any cause
Assessment of additional oncological and perioperative outcomes: Kind of oncological Re-interventions [y/n] 24 month Kind of interventions for treatment of intra- and/or extrahepatic disease recurrence will be documented. These interventions include: Chemotherapy, Surgical resection, Local ablation (e.g. radiofrequency or microwave ablation, stereotactic irradiation), Selective internal radiotherapy (SIRT), other
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Alanine-aminotransferase pre-operatively, 5 days after surgery Levels of alanine-aminotransferase (ALT) will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Gamma-glutamyl transferase pre-operatively, 5 days after surgery Levels of Gamma-glutamyl transferase (GGT) will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: International normalized ratio pre-operatively, 5 days after surgery Levels of international normalized ratio (INR) will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Total bilirubin pre-operatively, 5 days after surgery Levels of total bilirubin will be measured preoperatively and on postoperative day 5
Assessment of additional oncological and perioperative outcomes: Frequency of cancer-specific survival (CSS) 24 months The cancer-specific survival of all patients is assessed between operation date to date of death of colorectal cancer
Assessment of additional oncological and perioperative outcomes: Frequency of oncological Re-interventions [y/n] 24 month Frequency of interventions for treatment of intra- and/or extrahepatic disease recurrence will be documented. These interventions include: Chemotherapy, Surgical resection, Local ablation (e.g. radiofrequency or microwave ablation, stereotactic irradiation), Selective internal radiotherapy (SIRT), other
Assessment of additional oncological and perioperative outcomes: Kind of invasive re-interventions 30 days after surgery Invasive re-interventions such as placement of interventional drains, Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement, chest tube placement, and re-laparotomy within 30 days after the index operation or during patients' initial hospital stay
Assessment of additional oncological and perioperative outcomes: Administration of adjuvant therapy [y/n] 24 month Adjuvant therapy is not recommended. However, the decision for adjuvant therapy is left at discretion of the local oncologist. The administration of adjuvant therapy and kind of chemotherapy protocols used will be documented for both groups.
Assessment of additional oncological and perioperative outcomes: Number of patients with positive resection margins During surgery Detection of tumor at the resection margin will be counted as positive resection margin
Assessment of additional oncological and perioperative outcomes: Frequency of disease-free survival (DFS) 24 month The disease-free survival of all patients is assessed from operation date to the date of either progressive or recurrent disease, or death of any cause
Assessment of additional oncological and perioperative outcomes: Assessment of "Quality of life" (QoL) 12 month Quality of life is measured preoperatively and at 90 days (± 7 days) and 12 months (± 7 days) postoperatively using the EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer; Questionnaire for the assessment of Quality of Life of Cancer patients with the module dedicated to colorectal liver metastases (EORTC QLQ-LMC21); the questionnaire assesses multi-item scales, each item scoring from 1 to 4, a high score represents a high level of symptomatology or problems.
Trial Locations
- Locations (37)
Clinic for General, Vizeral and Transplant Surgery, Augsburg University Hospital
🇩🇪Augsburg, Germany
Surgical Clinic, Municipal Hospital Braunschweig gGmbH
🇩🇪Braunschweig, Germany
Surgical Clinic, Dortmund Hospital
🇩🇪Dortmund, Germany
Clinic for General and Visceral Surgery, Ulm University Medical Center
🇩🇪Ulm, Germany
LMU Munich Hospital, Clinic for General, Visceral and Transplant Surgery
🇩🇪Munich, Germany
Clinic for General, Visceral and Transplant Surgery, University Hospital Frankfurt, Goethe University Frankfurt am Main
🇩🇪Frankfurt, Germany
University Department of General, Visceral, Vascular and Transplant Surgery, Faculty of Medicine, Otto von Guericke University Magdeburg
🇩🇪Magdeburg, Germany
Clinic for General, Visceral and Pediatric Surgery, University Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Surgical Clinic, University Hospital Erlangen
🇩🇪Erlangen, Germany
Department of General, Visceral and Vascular Surgery, Charité, University Medicine Berlin, Campus Benjamin Franklin Berlin
🇩🇪Berlin, Germany
Department of General, Visceral and Transplantation Surgery, University of Heidelberg
🇩🇪Heidelberg, Germany
Department Hepato-Pancreato-Biliary Surgery, Barmherzige Brüder gGmbH of the Hospital Barmherzige Brüder Munich
🇩🇪München, Germany
General Visceral and Vascular Surgery, Jena University Medical Center
🇩🇪Jena, Germany
Clinic for Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg
🇩🇪Marburg, Germany
Clinic for Surgery, University Hospital Schleswig-Holstein Lübeck Campus
🇩🇪Lübeck, Germany
Clinic for General, Visceral and Transplantation Surgery, University Medical Center of the Johannes Gutenberg-University Mainz
🇩🇪Mainz, Germany
Department of Surgery, University Hospital rechts der Isar
🇩🇪München, Germany
Clinic for General, Visceral and Transplant Surgery, University of Münster
🇩🇪Münster, Germany
University Hospital for General and Visceral Surgery, Oldenburg Hospital
🇩🇪Oldenburg, Germany
Department of General, Visceral and Transplant Surgery, University of Tübingen, Comprehensive Cancer Center
🇩🇪Tübingen, Germany
General and Visceral Surgery, Helios University Medical Center Wuppertal, University Witten/Herdecke
🇩🇪Wuppertal, Germany
Department for General, Visceral, Transplant, Vascular and Pediatric Surgery, Julius-Maximilian-University Würzburg, University Hospital Würzburg
🇩🇪Würzburg, Germany
Clinic and Polyclinic for General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn
🇩🇪Bonn, Germany
Intestinal Center West Middle Franconia, ANregiomed Clinic Ansbach
🇩🇪Ansbach, Germany
Department of Gastrointestinal-, Thoracic and Vascular Surgery University Hospital Carl Gustav Carus Technische Universität Dresden
🇩🇪Dresden, Saxony, Germany
Cancer Center, Helios Amper-Hospital Dachau
🇩🇪Dachau, Germany
Clinic and Polyclinic for General Surgery, Department of Gastrointestinal, Thoracic and Vascular Surgery, University Greifswald, University Hospital Greifswald
🇩🇪Greifswald, Germany
Clinic for General and Visceral Surgery, Municipal Hospital Dresden
🇩🇪Dresden, Germany
Department for General and Visceral Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg
🇩🇪Freiburg, Germany
Clinic for General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Georg-August-University
🇩🇪Göttingen, Germany
JLU Gießen, Department for General, Visceral, Thoracic and Transplant Surgery
🇩🇪Gießen, Germany
University Hospital and Polyclinic for Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale)
🇩🇪Halle (Saale), Germany
Clinic for General, Visceral and Minimally Invasive Surgery, KRH Clinic Siloah, Hannover
🇩🇪Hannover, Germany
Center for Surgical Medicine - Clinic and Polyclinic for General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Department of Liver, Bile Duct and Pancreas Surgery, University Department of surgery, Asklepios Klinik Barmbek
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover, Department of General, Visceral and Transplant Surgery
🇩🇪Hannover, Germany
Department of Surgery at the University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University
🇩🇪Mannheim, Baden-Württemberg, Germany