Colorectal Cancer Metastatic
Conditions
Brief summary
230 patients with colorectal cancer liver metastases will be randomly assigned to resection or thermal ablation.
Detailed description
Rationale: The use of thermal ablation of liver tumors is rapidly increasing. This is despite a lack of high-level evidence of the oncologic efficacy of ablation. Ablation is most often used in cases where resection is not possible, but as the technique has improved it is increasingly used as a substitute for resection. A majority of studies on ablation are hampered by selection bias. Selection bias can only be overcome in a randomized controlled trial. Primary objective: To compare rates of local tumor progression within 12 months in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases. Secondary objectives: * To establish a pipeline for immediate three-dimensional verification of the ablated zone following thermal ablation of liver metastases. * To compare health related quality of life in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases. * To perform a cost-effectiveness analysis (Cost per quality adjusted life year) of thermal ablation and resection of colorectal liver metastases. * To compare disease-free and overall survival in in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases. * To evaluate the hemodynamic response to thermal ablation and laparoscopic resection of liver tumors. Study design: A randomized, controlled, multicenter, double-blinded non-inferiority trial. Study population: Two groups of 115 patients (230 in total) with colorectal liver metastasis eligible for radical treatment using EITHER resection OR ablation (not a combination). Intervention: Ablation of colorectal liver metastases Control: Resection of colorectal liver metastases Main study parameters/endpoints: The primary endpoint of the study is local recurrence of cancer at 12 months. Secondary endpoints include overall survival, disease free survival, health related quality of life, postoperative pain, complications, hospital stay and cost-effectiveness.
Interventions
PROCEDURESurgical resection
Resection of metastasis
PROCEDUREThermal ablation
Ablation of metastasis
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Masking will be performed by large drapings on wounds and masking of operation notes
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically verified colorectal cancer * Colorectal liver metastases (proven or suspected) eligible for radical treatment using EITHER resection OR ablation (not a combination), as decided by the liver MDT meeting at the study center * The patient is fit to undergo both resection and ablation of all liver metastases * Size of largest lesion up to and including 30 mm * In case of solitary metastasis, resection plan includes resection of ≤ 2 anatomical segments. * In case of multiple metastases in one continuous resection, resection plan can include ≤ 4 anatomical segments (including hemihepatectomy) * ≤ 5 tumors to be treated in one procedure * Primary tumor either resected (primary first) or with a plan for curative treatment (liver first).
Exclusion criteria
• More than 3 lung metastases where 1 is \>10mm, or 1 lung metastasis \>15 mm (OR: unresectable lung metastases as decided by the lung MDT meeting) * Presence of extrahepatic, extrapulmonary metastases. * Surgical indication for removal of enlarged lymph nodes in the hepatic hilum. (Enlarged lymph nodes without indication of removal are not considered an exclusion criterium) * Tumor closer than 10 mm to right/left main bile duct * Suspected tumor infiltration to adjacent organs * Progression (as of RECIST \[18\]) on 2nd line chemotherapy * Previous inclusion in this trial * Not eligible for workup according to study criteria * Contraindication to contrast enhanced CT scan * Manifest liver cirrhosis * Pregnancy * ECOG performance status ≥3 * Simultaneous resection of primary tumor or any other concomitant surgical procedure * Any other reason why, in the investigator's opinion, the patient should not be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local tumor progression | 12 months | Local tumor progression at site of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 60 months | Overall survival following treatment |
| Overall survival (secondary analysis) | 60 months | A secondary analysis will be performed on a oncologically more homogenous group of patients that fulfil the following requirements: a) no previous surgical procedure on the liver, b) no extrahepatic metastases, and c) that had their primary tumor resected |
| Disease free survival | 60 months | DFS |
| Postoperative complications | 30 days | Morbidity |
| Health related quality of life | 12 months | HRQoL is measured using SF-36 |
| Cost-Effectiveness | 12 months | An analysis of cost will be performed to assess cost-effectiveness |
| Ventilation methods | 1 day | The intraoperative movement of the liver will be measured using different ventilation methods (one lung ventilation, jet ventilation, gentle double lung ventilation). The movement of the liver during the different ventilation methods will be assessed in cm. |
| Cerebral flow | 1 day | Intraoperative cerebral blood flow will be measured and related to cardiac output and other hemodynamic measures. Micro bubbles caused by the treatment will be visualized using ultrasonography. |
| Hemodynamic response | 7 days | The hemodynamic response to the two interventions will be recorded and compared |
| Inflammatory response | 7 days | The inflammatory response (cytokines, complement, catecholamines) will be compared. |
Countries
Norway
Contacts
STUDY_DIRECTORBjørn Edwin, Professor
Head of clinical research, The Intervention Centre, Oslo University Hospital
Outcome results
None listed