Software-Aided Imaging (Morfeus) for Confirming Tumor Coverage With Ablation in Patients With Liver Tumors, the COVER-ALL Study

Study Overview
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Brief Summary
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This phase II trial studies how well software-aided imaging works in confirming tumor coverage with ablation (the removal or destruction of a body part or tissue or its function) on patients with liver tumors. The current standard for targeting tumor cells and evaluating the outcome of a liver ablation procedure is a visual inspection of the pre- and post-procedure computed tomography (CT) scans. Software-aided imaging systems, such as Morfeus, may help to improve the accuracy and effectiveness of liver ablation.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate if the intra-procedure feedback of a biomechanical deformable registration volumetric image method during percutaneous ablation will increase the minimal ablation margins on a three-dimensional computed tomography-generated analysis. SECONDARY OBJECTIVES: I. To assess whether applying the proposed method during percutaneous ablation improves local tumor progression-free survival (LTPFS) rates. II. Evaluate impact of software use on procedure workflow. III. Impact of software use on complication rates, quality of life, liver function. IV. Evaluate oncological outcomes (intra-hepatic and overall progression-free survivals, and overall survival). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo standard of care ablation. ARM II: Patients undergo standard of care ablation with software-aided imaging (Morfeus). After completion of study, patients are followed up at 1, 3, and 6 months, and then at 1 and 2 years.

Official Title
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Clinical Impact of a Volumetric Image Method for Confirming Tumor Coverage With Ablation on Patients With Malignant Liver Lesions (COVER-ALL)

Conditions
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Malignant Liver Neoplasm

Intervention / Treatment
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* Procedure: Ablation Therapy
* Procedure: Image-Guided Therapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with ≤ 3 liver tumors (biopsy-proven or documented by imaging) measuring 1 to 5 cm planned to undergo percutaneous thermal ablation with either microwave or radiofrequency ablation. Patients with more than 3 tumors might also be eligible in case other tumors can be treated with another curative-intended loco-regional therapy (i.e. surgical resection, radiation therapy). Ability to completely cover the target tumor with at least a 5 mm ablation margin. Written informed consent to voluntarily participate in the study and follow-up CT scan schedule Age > 18 years-old Performance status 0-2 (Eastern Cooperative Oncology Group Classification [ECOG]) Target tumor should be visualized on contrast-enhanced CT Adequate glomerular filtration rate Exclusion Criteria Active bacterial infection or fungal infection on the day of the ablation that, in the opinion of the investigator, would interfere with safe delivery of the study procedure or with the interpretation of study results. Platelet < 50,000/mm3. INR > 1.5 Patients with uncorrectable coagulopathy. Currently breastfeeding or pregnant (latter confirmed by serum pregnancy test). Physical or psychological condition which would impair study participation. ASA (American Society of Anesthesiologists) score of > 4. Any other loco-regional therapies at the target lesion(s) within 30 days of the ablation procedure.

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: Arm I (standard of care ablation)<br>Patients undergo standard of care ablation. | Procedure: Ablation Therapy<br>* Undergo standard of care ablation<br>* Other names: Local Ablative Therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (standard of care ablation, software-aided imaging)<br>Patients undergo standard of care ablation with software-aided imaging (Morfeus). | Procedure: Ablation Therapy<br>* Undergo standard of care ablation<br>* Other names: Local Ablative Therapy;Procedure: Image-Guided Therapy<br>* Undergo software-aided imaging (Morfeus)<br>* Other names: Imaging Guided Therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of software use on the minimal margins of ablated lesions properly covered by ablation on a three-dimensional analysis | Will assess whether applying biomechanical models increase the minimal margins of ablated lesions properly covered by ablation on a three-dimensional analysis. The average minimum ablation margins will be compared between two arms using a 2-sample t-test (or Wilcoxon rank-sum test). The means and corresponding 95% confidence intervals will be reported for both arms of the study. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tumor progression-free survival (LTPFS) | Kaplan-Meier method will be used to estimate LTPFS and 95% confidence intervals for the quantiles of the LTPFS function based on the method of Brookmeyer and Crowley will be calculated for each arm. | From date of ablation to earliest date of progression at the ablated lesion, assessed up to 2 years | 
| Intra-hepatic progression-free survival | Kaplan-Meier method will be used to estimate intra-hepatic progression-free survival and 95% confidence intervals for the quantiles of the intra-hepatic progression-free survival function based on the method of Brookmeyer and Crowley will be calculated for each arm. | From date of ablation to earliest date of progression at the ablated lesion, assessed up to 2 years | 
| Overall survival | Kaplan-Meier method will be used to estimate overall survival and 95% confidence intervals for the quantiles of the overall survival function based on the method of Brookmeyer and Crowley will be calculated for each arm. | From date of ablation to death, assessed up to 2 years | 
| Complication rates | Standard summary statistics will be computed for complication rates and compared between arms. | Up to 2 years | 
| Quality of life | Standard summary statistics will be computed for quality of life and compared between arms. | Up to 2 years | 
| Liver function | Standard summary statistics will be computed for liver function and compared between arms. | Up to 2 years |