Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer

Colorectal Liver Metastasis Clinical Trial

— ARMANI  

Official title:

Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04678583
• Other study ID #: VTG-08
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: Technische Universität Dresden
• Contact: Jürgen Weitz, Prof Dr med
• Phone: +49-(0)351 458 4850
• Email: juergen.weitz[@]ukdd.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Liver Metastasis
• Liver Neoplasms
• Neoplasm Metastasis

Intervention

Procedure:
• Resection of colorectal liver metastases
Comparison of two liver surgery methods

Locations

Country	Name	City	State
Germany	Intestinal Center West Middle Franconia, ANregiomed Clinic Ansbach	Ansbach
Germany	Clinic for General, Vizeral and Transplant Surgery, Augsburg University Hospital	Augsburg
Germany	Department of General, Visceral and Vascular Surgery, Charité, University Medicine Berlin, Campus Benjamin Franklin Berlin	Berlin
Germany	Clinic and Polyclinic for General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn	Bonn
Germany	Surgical Clinic, Municipal Hospital Braunschweig gGmbH	Braunschweig
Germany	Cancer Center, Helios Amper-Hospital Dachau	Dachau
Germany	Surgical Clinic, Dortmund Hospital	Dortmund
Germany	Clinic for General and Visceral Surgery, Municipal Hospital Dresden	Dresden
Germany	Department of Gastrointestinal-, Thoracic and Vascular Surgery University Hospital Carl Gustav Carus Technische Universität Dresden	Dresden	Saxony
Germany	Clinic for General, Visceral and Pediatric Surgery, University Hospital Düsseldorf	Düsseldorf
Germany	Surgical Clinic, University Hospital Erlangen	Erlangen
Germany	Clinic for General, Visceral and Transplant Surgery, University Hospital Frankfurt, Goethe University Frankfurt am Main	Frankfurt
Germany	Department for General and Visceral Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg	Freiburg
Germany	JLU Gießen, Department for General, Visceral, Thoracic and Transplant Surgery	Gießen
Germany	Clinic for General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Georg-August-University	Göttingen
Germany	Clinic and Polyclinic for General Surgery, Department of Gastrointestinal, Thoracic and Vascular Surgery, University Greifswald, University Hospital Greifswald	Greifswald
Germany	University Hospital and Polyclinic for Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale)	Halle (Saale)
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	Clinic for General, Visceral and Minimally Invasive Surgery, KRH Clinic Siloah, Hannover	Hannover
Germany	Medizinische Hochschule Hannover, Department of General, Visceral and Transplant Surgery	Hannover
Germany	Department of General, Visceral and Transplantation Surgery, University of Heidelberg	Heidelberg
Germany	General Visceral and Vascular Surgery, Jena University Medical Center	Jena
Germany	Clinic for Surgery, University Hospital Schleswig-Holstein Lübeck Campus	Lübeck
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 Transplantation Surgery, University Medical Center of the Johannes Gutenberg-University Mainz	Mainz
Germany	Department of Surgery at the University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University	Mannheim	Baden-Württemberg
Germany	Clinic for Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg	Marburg
Germany	Department Hepato-Pancreato-Biliary Surgery, Barmherzige Brüder gGmbH of the Hospital Barmherzige Brüder Munich	München
Germany	Department of Surgery, University Hospital rechts der Isar	München
Germany	LMU Munich Hospital, Clinic for General, Visceral and Transplant Surgery	Munich
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	Clinic for General and Visceral Surgery, Ulm University Medical Center	Ulm
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

Sponsors (3)

Lead Sponsor	Collaborator
Technische Universität Dresden	German Cancer Research Center, KKS Dresden

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 months
Secondary	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.	During surgery
Secondary	Assessment of additional oncological and perioperative outcomes: Operating time [min]	Time from skin incision until placement of last skin staple/suture.	During surgery
Secondary	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.	48 hours after surgery
Secondary	Assessment of additional oncological and perioperative outcomes: Duration of postoperative hospital stay [days]	Postoperative day 1 until day of discharge	At day of discharge, assessed up to 90 days
Secondary	Assessment of additional oncological and perioperative outcomes: Duration of postoperative intermediate/intensive care unit stay [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	At day of discharge, assessed up to 90 days
Secondary	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	90 days after surgery
Secondary	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	90 days after surgery
Secondary	Assessment of additional oncological and perioperative outcomes: 90-day mortality	Death due to any cause within 90 days after surgery	90 days after surgery
Secondary	Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Platelet count	Platelet count will be measured preoperatively and on postoperative day 5	pre-operatively, 5 days after surgery
Secondary	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	pre-operatively, 5 days after surgery
Secondary	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	pre-operatively, 5 days after surgery
Secondary	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	pre-operatively, 5 days after surgery
Secondary	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	pre-operatively, 5 days after surgery
Secondary	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	pre-operatively, 5 days after surgery
Secondary	Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Albumin	Levels of albumin will be measured preoperatively and on postoperative day 5	pre-operatively, 5 days after surgery
Secondary	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	30 days after surgery
Secondary	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	30 days after surgery
Secondary	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	During surgery
Secondary	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	24 month
Secondary	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	24 months
Secondary	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	24 month
Secondary	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.	24 month
Secondary	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	24 month
Secondary	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	24 month
Secondary	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.	12 month