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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
240
Comparison of two liver surgery methods
Intrahepatic disease-free survival (iDFS)
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.
Time frame: 24 months
Assessment of additional oncological and perioperative outcomes: Intraoperative blood loss [mL]
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.
Time frame: During surgery
Assessment of additional oncological and perioperative outcomes: Operating time [min]
Time from skin incision until placement of last skin staple/suture.
Time frame: During surgery
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]
Administration of blood transfusions is documented for the intra- and postoperative period within 48 hours postoperatively.
Time frame: 48 hours after surgery
Assessment of additional oncological and perioperative outcomes: Duration of postoperative hospital stay [days]
Postoperative day 1 until day of discharge
Time frame: At day of discharge, assessed up to 90 days
Assessment of additional oncological and perioperative outcomes: Duration of postoperative intermediate/intensive care unit stay [days]
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Department of Surgery at the University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University
Mannheim, Baden-Wurttemberg, Germany
RECRUITINGDepartment of Gastrointestinal-, Thoracic and Vascular Surgery University Hospital Carl Gustav Carus Technische Universität Dresden
Dresden, Saxony, Germany
RECRUITINGIntestinal Center West Middle Franconia, ANregiomed Clinic Ansbach
Ansbach, Germany
RECRUITINGClinic for General, Vizeral and Transplant Surgery, Augsburg University Hospital
Augsburg, Germany
RECRUITINGDepartment of General, Visceral and Vascular Surgery, Charité, University Medicine Berlin, Campus Benjamin Franklin Berlin
Berlin, Germany
RECRUITINGClinic and Polyclinic for General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn
Bonn, Germany
RECRUITINGSurgical Clinic, Municipal Hospital Braunschweig gGmbH
Braunschweig, Germany
RECRUITINGCancer Center, Helios Amper-Hospital Dachau
Dachau, Germany
RECRUITINGSurgical Clinic, Dortmund Hospital
Dortmund, Germany
RECRUITINGClinic for General and Visceral Surgery, Municipal Hospital Dresden
Dresden, Germany
RECRUITING...and 27 more locations
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
Time frame: At day of discharge, assessed up to 90 days
Assessment of additional oncological and perioperative outcomes: Frequency of peri-operative morbidity after resection
Frequency of peri-operative complications after resection of the primary tumor
Time frame: 90 days after surgery
Assessment of additional oncological and perioperative outcomes: Kind of peri-operative morbidity after resection
Kind of peri-operative complications after resection of the primary tumor
Time frame: 90 days after surgery
Assessment of additional oncological and perioperative outcomes: 90-day mortality
Death due to any cause within 90 days after surgery
Time frame: 90 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Platelet count
Platelet count will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Alanine-aminotransferase
Levels of alanine-aminotransferase (ALT) will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: aspartate-aminotransferase
Levels of aspartate-aminotransferase (AST) will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Gamma-glutamyl transferase
Levels of Gamma-glutamyl transferase (GGT) will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: International normalized ratio
Levels of international normalized ratio (INR) will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Total bilirubin
Levels of total bilirubin will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Albumin
Levels of albumin will be measured preoperatively and on postoperative day 5
Time frame: pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Frequency invasive re-interventions
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
Time frame: 30 days after surgery
Assessment of additional oncological and perioperative outcomes: Kind of invasive re-interventions
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
Time frame: 30 days after surgery
Assessment of additional oncological and perioperative outcomes: Number of patients with positive resection margins
Detection of tumor at the resection margin will be counted as positive resection margin
Time frame: During surgery
Assessment of additional oncological and perioperative outcomes: Frequency of Overall survival (OS)
The overall survival of all patients is assessed between operation date to date of death of any cause
Time frame: 24 month
Assessment of additional oncological and perioperative outcomes: Frequency of cancer-specific survival (CSS)
The cancer-specific survival of all patients is assessed between operation date to date of death of colorectal cancer
Time frame: 24 months
Assessment of additional oncological and perioperative outcomes: Frequency of disease-free survival (DFS)
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
Time frame: 24 month
Assessment of additional oncological and perioperative outcomes: Administration of adjuvant therapy [y/n]
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.
Time frame: 24 month
Assessment of additional oncological and perioperative outcomes: Frequency of oncological Re-interventions [y/n]
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
Time frame: 24 month
Assessment of additional oncological and perioperative outcomes: Kind of oncological Re-interventions [y/n]
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
Time frame: 24 month
Assessment of additional oncological and perioperative outcomes: Assessment of "Quality of life" (QoL)
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.
Time frame: 12 month