Colorectal Liver Metastasis
Conditions
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.
Interventions
PROCEDUREResection of colorectal liver metastases
Comparison of two liver surgery methods
Sponsors
German Cancer Research Center
Technische Universität Dresden
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomized, controlled, patient and observer-blinded, confirmatory trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: Operating time [min] | During surgery | Time from skin incision until placement of last skin staple/suture. |
| 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: 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: 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: 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: 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: 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: 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: 90-day mortality | 90 days after surgery | Death due to any cause within 90 days after surgery |
| 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: 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: 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: 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 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: 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 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: 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: 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 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: 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. |
| 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 |
Countries
Germany
Contacts
Primary ContactJürgen Weitz, Prof Dr med
Outcome results
None listed