Clinical trial NCT04081168: COLLISION XL: Unresectable Colorectal Liver Metastases (3-5cm): Stereotactic Body Radiotherapy vs. Microwave Ablation
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colorectal Cancer Metastatic
Liver Metastasis Colon Cancer
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stereotactic Body Radiotherapy vs. Microwave Ablation
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: One-year local tumor progression-free survival
timeFrame: 1 year
Secondary outcomes:
measure: Timo-to-local tumor progression
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Disease-Free Survival (DFS)
timeFrame: 5 years
measure: Mortality
timeFrame: 5 years
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord Holland
Study officials:
References: