A Trial on SBRT Versus MWA for Inoperable Colorectal Liver Metastases (CLM)

Study Overview
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Brief Summary
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The trial is designed to perform a rigorous evaluation of efficacy and tolerability of SBRT by means of a randomised, controlled trial in patients affected by inoperable colorectal liver metastases. The chosen comparator is MWA. The two modality treatments (SBRT versus MWA) will be evaluated for short- and longer-term outcomes.

Detailed Description
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The trial is a monocentric prospective, randomised controlled, unblinded, parallel-group superiority trial of Stereotactic Body Radiation Therapy (SBRT) versus Microwave Ablation (MWA) for the curative treatment of inoperable colorectal liver metastases. Patients will be randomised on an equal basis to either SBRT or MWA. The two modality treatments (SBRT versus MWA) will be evaluated for short- and longer-term outcomes. The key short-term outcomes will include assessment of local response rate and acute toxicity. Longer-term outcomes will concentrate on oncological aspects of the disease with analysis of disease-free and overall survival and local recurrence rates at 3-year follow-up.

Official Title
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A Randomized Phase III Trial on Stereotactic Body Radiation Therapy (SBRT) Versus Microwave Ablation (MWA) for Inoperable Colorectal Liver Metastases (CLM)

Conditions
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Secondary Malignant Neoplasm of Liver

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy
* Procedure: Microwave Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Karnofsky index >70% Histological proven adenocarcinoma of the colon or rectum with radiological (by CT- or MRI) or histological-/cytological verified liver metastases. Metastases must be visible on diagnostic- and dose planning CT scans and on ultrasonography. The patient should not be suitable for surgical resection due to technical or patient-related conditions. Resectability must be judged by a trained hepatobiliary surgeon and discussed in a multidisciplinary team meeting. Presence of 1-3 lesions . Diameter ≤ 40 mm. All tumors should be feasible for treatment with each of the two modalities, SBRT and MWA Adequate liver function: bilirubin <1.5 mg/dl, alb> 3.5g/dl, normal PT/PTT except if the patient uses anticoagulants, liver enzymes<3 times upper limit of normal. No ascites. Renal function must be adequate for infusion of iv. contrast for CT-scan. Adequate bone marrow function: Hbg³8 g/dl, platelets³100.000 and leucocytes ³2.000/ml. Informed consent. Extrahepatic disease stable or in response after CT No previous abdominal radiation therapy (RT) Exclusion Criteria: Uncontrolled primary tumor or extrahepatic disease Previous abdominal radiation therapy (RT) or other local conservative treatment on lesion target. Pregnant or breastfeeding patients. Prior malignancy within the last five years (except adequately treated basal cell carcinoma of the skin or in situ carcinoma of the skin or in situ carcinoma of the cervix, surgically cured, or localized prostate cancer without evidence of biochemical progression). Previous inclusion in this study. Underlying liver cirrhosis (Child-Pugh grade B or C). Ascites and/or relevant intra-hepatic biliary tract dilatation. Mental conditions rendering the patient incapable to understand the nature, scope, and consequences of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stereotactic body radiation therapy<br>Patients are treated with Stereotactic Body Radiation Therapy, a methodology for delivering a conformal high dose of radiation to the tumor and a minimal dose to surrounding critical tissues, with a hypofractionation schedule. | Radiation: Stereotactic Body Radiation Therapy<br>* Stereotactic body radiation is a therapy for delivering a conformal high dose of radiation to the tumor and a minimal dose to surrounding critical tissues, with a hypofractionation schedule<br>|
| Active Comparator: Microwave Ablation<br>Patients are treated with Microwave Ablation,a newer technology that utilizes high-frequency electromagnetic radiation to create thermal damage and coagulation necrosis. | Procedure: Microwave Ablation<br>* Microwave ablation (MWA) is a newer technology that utilizes high-frequency electromagnetic radiation to create thermal damage and coagulation necrosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Control of local disease | Evaluation of proportion of patients free from progression from starting radiotherapy | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free-survival of treated patients | Evaluation of proportion of patients alive and free from progression | 18 months | 
| Overall survival of treated patients | Evaluation of proportion of patients alive | 18 months | 
| Incidence of acute and late complications | Evaluation of early and late post treatment complications | 18 months |