Stereotactic Body Radiation Therapy vs. Microwave Ablation for Colorectal Cancer Patients With Metastatic Disease in the Liver

Study Overview
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Brief Summary
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This study is a randomized phase II trial between microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) - two standard treatment modalities for colorectal patients with metastatic disease in the liver. Primary endpoint is freedom form local lesion progression.

Detailed Description
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Colorectal cancer patients with 1-3 liver metastases (diameter ≤4.0 cm) found unsuitable for resection are randomized 1:1 to either MWA or SBRT. Chemotherapy is allowed. Curative treatment of extrahepatic disease must be initiated in patients with lung metastases and/or primary tumors. Patients will be analyzed according to the intention-to-treat principle.

Official Title
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Stereotactic Body Radiation Therapy vs. Microwave Ablation for Colorectal Cancer Patients With Metastatic Disease in the Liver - a Randomized Phase II Trail

Conditions
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Colorectal Carcinoma, Liver Metastases

Intervention / Treatment
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* Device: MWA
* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Colorectal cancer patients with oligo metastatic disease in the liver (1 to 3 tumors), and where metastases are found unsuitable for resection because of non-resectability small metastasis localized deep in the liver, where a parenchyma sparing intervention is preferred over an extensive resection previous extensive liver surgery comorbidity The multidisciplinary team should all agree that both percutaneous or open surgical MW-ablation and SBRT are safe as first treatment choice for the individual patient. Tumor sizes ≤4.0 cm Age > 18 years Signed informed consent Exclusion Criteria: Previous radiotherapy to the liver Liver volume < 700 ml Another active cancer disease within the past 36 months Not able to understand written or oral protocol information

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: MWA<br>Percutaneous ultrasound-guided MWA or open surgery MWA. The patient is fully anesthetized during the treatment. | Device: MWA<br>* Patients are allocated to one of the two arms in a 1:1 randomization<br>|
| Active Comparator: SBRT<br>3 fractions of 15 Gy (in total 45 Gy), 3 fractions per week. The dose is prescribed to the PTV encompassing 67% isodose. The SBRT plan is normalized such that the mean dose to the GTV is 100% = 67.5 Gy. | Radiation: SBRT<br>* Patients are allocated to one of the two arms in a 1:1 randomization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from local lesion progression (analyzed on patient-level) | Defined as the time from randomization to local progression Censoring: death from any cause, last follow-up No censoring on disease progression outside of the treated lesions Local lesion progression is defined as >20% increase in the longest diameter and minimum 5 mm increase talking as reference the smallest longest diameter recorded since the treatment started in any of the treated lesions | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Defined as the time from randomization to death from any cause Censoring: last follow-up | 3 years | 
| Freedom from local lesion progression (analyzed on lesion-level) | Defined as the time from randomization to local progression Censoring: death from any cause, last follow-up No censoring on disease progression outside of the treated lesions Local lesion progression is defined as >20% increase in the longest diameter and minimum 5 mm increase talking as reference the smallest longest diameter recorded since the treatment started in any of the treated lesions | 3 years | 
| ≥ grade 3 toxicity potentially associated with the treatment | Defined as the time from randomization to first ≥ grade 3 toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Censoring: death from any cause, last follow-up | 3 years | 
| Toxicity profile as descriptive statistics | Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 3 years | 
| Quality of life as descriptive statistics: EORTC QLQ-C30 | Using EORTC QLQ-C30 | 3 years |