Clinical trial NCT04678583: Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer
Official title: Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Liver Metastasis
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: German Cancer Research Center
First posted: 2020-12-22
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, patient and observer-blinded, confirmatory trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Intrahepatic disease-free survival (iDFS)
timeFrame: 24 months
Secondary outcomes:
measure: Assessment of additional oncological and perioperative outcomes: Intraoperative blood loss [mL]
timeFrame: During surgery
measure: Assessment of additional oncological and perioperative outcomes: Operating time [min]
timeFrame: During surgery
measure: 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]
timeFrame: 48 hours after surgery
measure: Assessment of additional oncological and perioperative outcomes: Duration of postoperative hospital stay [days]
timeFrame: At day of discharge, assessed up to 90 days
measure: Assessment of additional oncological and perioperative outcomes: Duration of postoperative intermediate/intensive care unit stay [days]
timeFrame: At day of discharge, assessed up to 90 days
measure: Assessment of additional oncological and perioperative outcomes: Frequency of peri-operative morbidity after resection
timeFrame: 90 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Kind of peri-operative morbidity after resection
timeFrame: 90 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: 90-day mortality
timeFrame: 90 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Platelet count
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Alanine-aminotransferase
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: aspartate-aminotransferase
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Gamma-glutamyl transferase
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: International normalized ratio
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Total bilirubin
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Albumin
timeFrame: pre-operatively, 5 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Frequency invasive re-interventions
timeFrame: 30 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Kind of invasive re-interventions
timeFrame: 30 days after surgery
measure: Assessment of additional oncological and perioperative outcomes: Number of patients with positive resection margins
timeFrame: During surgery
measure: Assessment of additional oncological and perioperative outcomes: Frequency of Overall survival (OS)
timeFrame: 24 month
measure: Assessment of additional oncological and perioperative outcomes: Frequency of cancer-specific survival (CSS)
timeFrame: 24 months
measure: Assessment of additional oncological and perioperative outcomes: Frequency of disease-free survival (DFS)
timeFrame: 24 month
measure: Assessment of additional oncological and perioperative outcomes: Administration of adjuvant therapy [y/n]
timeFrame: 24 month
measure: Assessment of additional oncological and perioperative outcomes: Frequency of oncological Re-interventions [y/n]
timeFrame: 24 month
measure: Assessment of additional oncological and perioperative outcomes: Kind of oncological Re-interventions [y/n]
timeFrame: 24 month
measure: Assessment of additional oncological and perioperative outcomes: Assessment of "Quality of life" (QoL)
timeFrame: 12 month
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Department of Surgery at the University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University
state: Baden-Württemberg
city: Dresden
country: Germany
facility: Department of Gastrointestinal-, Thoracic and Vascular Surgery University Hospital Carl Gustav Carus Technische Universität Dresden
state: Saxony
city: Ansbach
country: Germany
facility: Intestinal Center West Middle Franconia, ANregiomed Clinic Ansbach
city: Augsburg
country: Germany
facility: Clinic for General, Vizeral and Transplant Surgery, Augsburg University Hospital
city: Berlin
country: Germany
facility: Department of General, Visceral and Vascular Surgery, Charité, University Medicine Berlin, Campus Benjamin Franklin Berlin
city: Bonn
country: Germany
facility: Clinic and Polyclinic for General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn
city: Braunschweig
country: Germany
facility: Surgical Clinic, Municipal Hospital Braunschweig gGmbH
city: Dachau
country: Germany
facility: Cancer Center, Helios Amper-Hospital Dachau
city: Dortmund
country: Germany
facility: Surgical Clinic, Dortmund Hospital
city: Dresden
country: Germany
facility: Clinic for General and Visceral Surgery, Municipal Hospital Dresden
city: Düsseldorf
country: Germany
facility: Clinic for General, Visceral and Pediatric Surgery, University Hospital Düsseldorf
city: Erlangen
country: Germany
facility: Surgical Clinic, University Hospital Erlangen
city: Frankfurt
country: Germany
facility: Clinic for General, Visceral and Transplant Surgery, University Hospital Frankfurt, Goethe University Frankfurt am Main
city: Freiburg
country: Germany
facility: Department for General and Visceral Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg
city: Gießen
country: Germany
facility: JLU Gießen, Department for General, Visceral, Thoracic and Transplant Surgery
city: Greifswald
country: Germany
facility: Clinic and Polyclinic for General Surgery, Department of Gastrointestinal, Thoracic and Vascular Surgery, University Greifswald, University Hospital Greifswald
city: Göttingen
country: Germany
facility: Clinic for General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Georg-August-University
city: Halle (Saale)
country: Germany
facility: University Hospital and Polyclinic for Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale)
city: Hamburg
country: Germany
facility: Center for Surgical Medicine - Clinic and Polyclinic for General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Department of Liver, Bile Duct and Pancreas Surgery, University Department of surgery, Asklepios Klinik Barmbek
city: Hannover
country: Germany
facility: Clinic for General, Visceral and Minimally Invasive Surgery, KRH Clinic Siloah, Hannover
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Department of General, Visceral and Transplant Surgery
city: Heidelberg
country: Germany
facility: Department of General, Visceral and Transplantation Surgery, University of Heidelberg
city: Jena
country: Germany
facility: General Visceral and Vascular Surgery, Jena University Medical Center
city: Lübeck
country: Germany
facility: Clinic for Surgery, University Hospital Schleswig-Holstein Lübeck Campus
city: Magdeburg
country: Germany
facility: University Department of General, Visceral, Vascular and Transplant Surgery, Faculty of Medicine, Otto von Guericke University Magdeburg
city: Mainz
country: Germany
facility: Clinic for General, Visceral and Transplantation Surgery, University Medical Center of the Johannes Gutenberg-University Mainz
city: Marburg
country: Germany
facility: Clinic for Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg
city: Munich
country: Germany
facility: LMU Munich Hospital, Clinic for General, Visceral and Transplant Surgery
city: München
country: Germany
facility: Department Hepato-Pancreato-Biliary Surgery, Barmherzige Brüder gGmbH of the Hospital Barmherzige Brüder Munich
city: München
country: Germany
facility: Department of Surgery, University Hospital rechts der Isar
city: Münster
country: Germany
facility: Clinic for General, Visceral and Transplant Surgery, University of Münster
city: Oldenburg
country: Germany
facility: University Hospital for General and Visceral Surgery, Oldenburg Hospital
city: Tübingen
country: Germany
facility: Department of General, Visceral and Transplant Surgery, University of Tübingen, Comprehensive Cancer Center
city: Ulm
country: Germany
facility: Clinic for General and Visceral Surgery, Ulm University Medical Center
city: Wuppertal
country: Germany
facility: General and Visceral Surgery, Helios University Medical Center Wuppertal, University Witten/Herdecke
city: Würzburg
country: Germany
facility: Department for General, Visceral, Transplant, Vascular and Pediatric Surgery, Julius-Maximilian-University Würzburg, University Hospital Würzburg
Study officials:
affiliation: Department of Gastrointestinal-, Thoracic and Vascular Surgery, University Hospital CGC
name: Jürgen Weitz, Prof Dr med
role: PRINCIPAL_INVESTIGATOR
affiliation: Allgemein- und Viszeralchirugie, University Hospital Ulm
name: Nuh Rahbari, Prof Dr med
role: PRINCIPAL_INVESTIGATOR
References: