COLLISION XL: Unresectable Colorectal Liver Metastases (3-5cm): Stereotactic Body Radiotherapy vs. Microwave Ablation

Study Overview
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Brief Summary
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Multiple articles report that thermal ablation is a safe and effective treatment for unresectable colorectal liver metastases (CRLM) ≤3cm. However efficacy of thermal ablation decreases with increasing lesion size. Guidelines state that thermal ablation is the preferred option for unresectable CRLM ≤3cm and stereotactic body radiotherapy (SBRT) when thermal ablation is not possible. It remains uncertain what local treatment method should be recommended for unresectable CRLM of 3-5cm.

Detailed Description
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Objective: The primary objective of this study is to compare efficacy of MWA to the efficacy of SBRT with regards to the primary endpoint (local tumour progression free survival at 1 year [1-year LTPFS]) in patients with unresectable CRLM (3 - 5 cm) that are unsuitable for surgery due to either comorbidities, a history of extensive abdominal surgery, a poor performance status or due to a certain unfavourable anatomical location of the tumour. Study design: COLLISION XL is a prospective multi-centre phase-II randomized controlled trial. Study population: 68 patients with 1-3 unresectable lesions of 3 - 5cm, unsuitable for (further) chemotherapy regimens, suitable for both MWA and SBRT and no or limited extrahepatic disease (1 extrahepatic lesion is allowed, not including positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis) are considered eligible. Supplementary resections for resectable lesions and thermal ablations for unresectable CRLM ≤3cm are allowed. A maximum number of 10 CRLM are allowed for patients with no extrahepatic disease and a maximum number of 5 lesions are allowed for patients with limited extrahepatic disease. Intervention: SBRT or MWA. The panel, consisting of at least two interventional radiologists, two hepatobiliary surgeons and two radiation oncologists, will appoint lesions of 3-5cm that are unresectable and suitable for both MWA and SBRT, as target lesions. All lesions that are not suitable for ablation should be resectable and all unresectable lesions <3cm should be suitable for thermal ablation. Main study parameters/endpoints: Primary endpoint is local tumour progression free survival (LTPFS) at 1 year from randomization. Secondary endpoints are local tumour progression free survival time, OS, disease-free survival (DFS), time to progression (TTP), procedural morbidity/toxicity and mortality, assessment of pain and quality of life (QoL) and cost-effectiveness ratio (ICER).

Official Title
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COLLISION XL: Unresectable Colorectal Liver Metastases: Stereotactic Body Radiotherapy vs. Microwave Ablation - a Phase II Prospective Randomized Controlled Trial for Intermediate-size (3 - 5 cm) Colorectal Liver Metastases

Conditions
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Colorectal Cancer Metastatic, Liver Metastasis Colon Cancer

Intervention / Treatment
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* Device: Stereotactic Body Radiotherapy
* Device: Microwave Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1-3 unresectable CRLM size 3-5 cm eligible for both MWA and SBRT (target lesions); Additional CRLM are allowed if considered either resectable or ablatable and <3cm No or limited extrahepatic disease (1 extrahepatic lesion is allowed, not including positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis); For subjects with liver only disease the maximum number of CRLM is 10; for subjects with limited extrahepatic disease the maximum number of CRLM is 5; Prior focal liver treatment is allowed Subjects without prior focal liver treatment should be either unsuitable for 1st line chemotherapy or have progressed under/after 1st-line chemotherapy; Subjects with recurrent (either local or distant-hepatic) CRLM after previous focal treatment should be unsuitable for (further) systemic therapy (further downsizing or conversion to resectable disease improbable). Exclusion Criteria: Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites); Pregnant or breast-feeding subjects; Immunotherapy ≤ 6 weeks prior to the procedure; Chemotherapy ≤ 6 weeks prior to the procedure; Severe allergy to contrast media not controlled with premedication.

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
Interventional Model Description: Stereotactic Body Radiotherapy vs. Microwave Ablation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stereotactic Body Radiotherapy<br>Patients included will undergo Stereotactic Body Radiotherapy (SBRT) of hepatic metastases. | Device: Stereotactic Body Radiotherapy<br>* Patients will undergo Stereotactic Body Radiotherapy (SBRT)<br>* Other names: SBRT;|
| Active Comparator: Microwave Ablation<br>Patients included will undergo Microwave Ablation (MWA) of hepatic metastases. | Device: Microwave Ablation<br>* Patients will undergo Microwave Ablation (MWA)<br>* Other names: MWA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One-year local tumor progression-free survival | One-year local tumor progression-free survival | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timo-to-local tumor progression | Timo-to-local tumor progression | 5 years | 
| Overall survival (OS) | Overall survival (OS) | 5 years | 
| Disease-Free Survival (DFS) | Disease-Free Survival (DFS) | 5 years | 
| Mortality | Mortality | 5 years |