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

June 12, 2024 updated by: Technische Universität Dresden
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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
240

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Germany
      • Ansbach, Germany
        • Recruiting
        • Intestinal Center West Middle Franconia, ANregiomed Clinic Ansbach
      • Augsburg, Germany
        • Recruiting
        • Clinic for General, Vizeral and Transplant Surgery, Augsburg University Hospital
      • Berlin, Germany
        • Recruiting
        • Department of General, Visceral and Vascular Surgery, Charité, University Medicine Berlin, Campus Benjamin Franklin Berlin
      • Bonn, Germany
        • Recruiting
        • Clinic and Polyclinic for General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn
      • Braunschweig, Germany
        • Recruiting
        • Surgical Clinic, Municipal Hospital Braunschweig gGmbH
      • Dachau, Germany
        • Recruiting
        • Cancer Center, Helios Amper-Hospital Dachau
      • Dortmund, Germany
        • Recruiting
        • Surgical Clinic, Dortmund Hospital
      • Dresden, Germany
        • Recruiting
        • Clinic for General and Visceral Surgery, Municipal Hospital Dresden
      • Düsseldorf, Germany
        • Recruiting
        • Clinic for General, Visceral and Pediatric Surgery, University Hospital Düsseldorf
      • Erlangen, Germany
        • Recruiting
        • Surgical Clinic, University Hospital Erlangen
      • Frankfurt, Germany
        • Recruiting
        • Clinic for General, Visceral and Transplant Surgery, University Hospital Frankfurt, Goethe University Frankfurt am Main
      • Freiburg, Germany
        • Recruiting
        • Department for General and Visceral Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg
      • Gießen, Germany
        • Recruiting
        • JLU Gießen, Department for General, Visceral, Thoracic and Transplant Surgery
      • Greifswald, Germany
        • Recruiting
        • Clinic and Polyclinic for General Surgery, Department of Gastrointestinal, Thoracic and Vascular Surgery, University Greifswald, University Hospital Greifswald
      • Göttingen, Germany
        • Recruiting
        • Clinic for General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Georg-August-University
      • Halle (Saale), Germany
        • Recruiting
        • University Hospital and Polyclinic for Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale)
      • Hamburg, Germany
        • Recruiting
        • Department of Liver, Bile Duct and Pancreas Surgery, University Department of surgery, Asklepios Klinik Barmbek
      • Hamburg, Germany
        • Recruiting
        • Center for Surgical Medicine - Clinic and Polyclinic for General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf
      • Hannover, Germany
        • Recruiting
        • Medizinische Hochschule Hannover, Department of General, Visceral and Transplant Surgery
      • Hannover, Germany
        • Recruiting
        • Clinic for General, Visceral and Minimally Invasive Surgery, KRH Clinic Siloah, Hannover
      • Heidelberg, Germany
        • Recruiting
        • Department of General, Visceral and Transplantation Surgery, University of Heidelberg
      • Jena, Germany
        • Recruiting
        • General Visceral and Vascular Surgery, Jena University Medical Center
      • Lübeck, Germany
        • Recruiting
        • Clinic for Surgery, University Hospital Schleswig-Holstein Lübeck Campus
      • Magdeburg, Germany
        • Recruiting
        • University Department of General, Visceral, Vascular and Transplant Surgery, Faculty of Medicine, Otto von Guericke University Magdeburg
      • Mainz, Germany
        • Recruiting
        • Clinic for General, Visceral and Transplantation Surgery, University Medical Center of the Johannes Gutenberg-University Mainz
      • Marburg, Germany
        • Recruiting
        • Clinic for Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg
      • Munich, Germany
        • Recruiting
        • LMU Munich Hospital, Clinic for General, Visceral and Transplant Surgery
      • München, Germany
        • Recruiting
        • Department of Surgery, University Hospital rechts der Isar
      • München, Germany
        • Recruiting
        • Department Hepato-Pancreato-Biliary Surgery, Barmherzige Brüder gGmbH of the Hospital Barmherzige Brüder Munich
      • Münster, Germany
        • Recruiting
        • Clinic for General, Visceral and Transplant Surgery, University of Münster
      • Oldenburg, Germany
        • Withdrawn
        • University Hospital for General and Visceral Surgery, Oldenburg Hospital
      • Tübingen, Germany
        • Recruiting
        • Department of General, Visceral and Transplant Surgery, University of Tübingen, Comprehensive Cancer Center
      • Ulm, Germany
        • Recruiting
        • Clinic for General and Visceral Surgery, Ulm University Medical Center
      • Wuppertal, Germany
        • Recruiting
        • General and Visceral Surgery, Helios University Medical Center Wuppertal, University Witten/Herdecke
      • Würzburg, Germany
        • Recruiting
        • Department for General, Visceral, Transplant, Vascular and Pediatric Surgery, Julius-Maximilian-University Würzburg, University Hospital Würzburg
    • Baden-Württemberg
      • Mannheim, Baden-Württemberg, Germany, 68167
        • Recruiting
        • Department of Surgery at the University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University
        • Contact:
          • Nuh Rahbari, PD Dr. med.
          • Phone Number: +49-(0)621 383 3591
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Recruiting
        • Department of Gastrointestinal-, Thoracic and Vascular Surgery University Hospital Carl Gustav Carus Technische Universität Dresden
        • Contact:
          • Jürgen Weitz, Prof Dr med
        • Contact:
          • Secretary
          • Phone Number: +49-(0)351 458 4850

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A - Anatomical resection
removal of the entire, tumor-bearing liver segment(s)
Procedure: Resection of colorectal liver metastases
Comparison of two liver surgery methods
Active Comparator: B - Non-anatomical resection
metastasectomy with a margin of healthy liver tissue irrespective of segmental borders
Procedure: Resection of colorectal liver metastases
Comparison of two liver surgery methods

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Intrahepatic disease-free survival (iDFS)
Time Frame: 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.
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assessment of additional oncological and perioperative outcomes: Intraoperative blood loss [mL]
Time Frame: 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.
During surgery
Assessment of additional oncological and perioperative outcomes: Operating time [min]
Time Frame: During surgery
Time from skin incision until placement of last skin staple/suture.
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]
Time Frame: 48 hours after surgery
Administration of blood transfusions is documented for the intra- and postoperative period within 48 hours postoperatively.
48 hours after surgery
Assessment of additional oncological and perioperative outcomes: Duration of postoperative hospital stay [days]
Time Frame: At day of discharge, assessed up to 90 days
Postoperative day 1 until day of discharge
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]
Time Frame: 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
At day of discharge, assessed up to 90 days
Assessment of additional oncological and perioperative outcomes: Frequency of peri-operative morbidity after resection
Time Frame: 90 days after surgery
Frequency of peri-operative complications after resection of the primary tumor
90 days after surgery
Assessment of additional oncological and perioperative outcomes: Kind of peri-operative morbidity after resection
Time Frame: 90 days after surgery
Kind of peri-operative complications after resection of the primary tumor
90 days after surgery
Assessment of additional oncological and perioperative outcomes: 90-day mortality
Time Frame: 90 days after surgery
Death due to any cause within 90 days after surgery
90 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Alanine-aminotransferase
Time Frame: pre-operatively, 5 days after surgery
Levels of alanine-aminotransferase (ALT) will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: aspartate-aminotransferase
Time Frame: pre-operatively, 5 days after surgery
Levels of aspartate-aminotransferase (AST) will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Gamma-glutamyl transferase
Time Frame: pre-operatively, 5 days after surgery
Levels of Gamma-glutamyl transferase (GGT) will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: International normalized ratio
Time Frame: pre-operatively, 5 days after surgery
Levels of international normalized ratio (INR) will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Total bilirubin
Time Frame: pre-operatively, 5 days after surgery
Levels of total bilirubin will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Albumin
Time Frame: pre-operatively, 5 days after surgery
Levels of albumin will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery
Assessment of additional oncological and perioperative outcomes: Frequency invasive re-interventions
Time Frame: 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
30 days after surgery
Assessment of additional oncological and perioperative outcomes: Kind of invasive re-interventions
Time Frame: 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
30 days after surgery
Assessment of additional oncological and perioperative outcomes: Number of patients with positive resection margins
Time Frame: During surgery
Detection of tumor at the resection margin will be counted as positive resection margin
During surgery
Assessment of additional oncological and perioperative outcomes: Frequency of Overall survival (OS)
Time Frame: 24 month
The overall survival of all patients is assessed between operation date to date of death of any cause
24 month
Assessment of additional oncological and perioperative outcomes: Frequency of cancer-specific survival (CSS)
Time Frame: 24 months
The cancer-specific survival of all patients is assessed between operation date to date of death of colorectal cancer
24 months
Assessment of additional oncological and perioperative outcomes: Frequency of disease-free survival (DFS)
Time Frame: 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
24 month
Assessment of additional oncological and perioperative outcomes: Administration of adjuvant therapy [y/n]
Time Frame: 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.
24 month
Assessment of additional oncological and perioperative outcomes: Frequency of oncological Re-interventions [y/n]
Time Frame: 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
24 month
Assessment of additional oncological and perioperative outcomes: Kind of oncological Re-interventions [y/n]
Time Frame: 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
24 month
Assessment of additional oncological and perioperative outcomes: Assessment of "Quality of life" (QoL)
Time Frame: 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.
12 month
Assessment of additional oncological and perioperative outcomes: Liver biochemical tests: Platelet count
Time Frame: pre-operatively, 5 days after surgery
Platelet count will be measured preoperatively and on postoperative day 5
pre-operatively, 5 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Technische Universität Dresden

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
German Cancer Research Center
KKS Dresden

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jürgen Weitz, Prof Dr med, Department of Gastrointestinal-, Thoracic and Vascular Surgery, University Hospital CGC
  • Principal Investigator: Nuh Rahbari, Prof Dr med, Allgemein- und Viszeralchirugie, University Hospital Ulm

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 30, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 22, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 12, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VTG-08

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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