Malignant Liver NeoplasmPhase 2NCT04083378
Software-Aided Imaging (Morfeus) for Confirming Tumor Coverage With Ablation in Patients With Liver Tumors, the COVER-ALL Study
A Phase 2 study testing Ablation Therapy, Image-Guided Therapy and Quality-of-Life Assessment in people with Malignant Liver Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Liver Neoplasm
- What is being tested?
- Ablation Therapy, Image-Guided Therapy and Quality-of-Life Assessment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2020to 31 Oct 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Impact of a Volumetric Image Method for Confirming Tumor Coverage With Ablation on Patients With Malignant Liver Lesions (COVER-ALL)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- Conditions
- Malignant Liver Neoplasm
- Being tested
- Ablation Therapy, Image-Guided Therapy, Quality-of-Life Assessment, Questionnaire Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ablation TherapyProcedure or surgery
Also called ABLATION, Catheter Ablation, Local Ablation Therapy, Local Ablative Therapy
Undergo standard of care ablation
Image-Guided TherapyProcedure or surgery
Also called Image Guided Therapy, Imaging Guided Therapy
Undergo software-aided imaging (Morfeus)
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (standard of care ablation) | Active comparator | Patients undergo standard of care ablation. Receives: Procedure: Ablation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Arm II (standard of care ablation, software-aided imaging) | Experimental | Patients undergo standard of care ablation with software-aided imaging (Morfeus). Receives: Procedure: Ablation Therapy; Procedure: Image-Guided Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal Ablative Margin Assessment on Post-ablation Intraprocedural CT.
For control group, MAM was assessed by rigid co-registration with side-by-side juxtaposition to verify applicator placement and by visual landmark-based CT measurements on CT workstation (Siemens Healthineers; Forchheim, Germany). For experimental group, CT images were processed with a software-based method on a radiation treatment planning system (Raystation, RaySearch Laboratories; Stockholm, Sweden) with biomechanical deformable imaging registration coupled with AI-based autosegmentation. For experimental group, interventional radiologist (IR) was informed of ablation applicator position relative to tumor on non-contrast CT before thermal ablation energy delivery and of MAM results (including spatial location of suboptimal margins) generated by software-based assessment, with this information not disclosed to IR in control group. Software-based assessment was used to compare MAMs results between both study groups with a two-sample t-test.
Measured: Visit 2 (baseline/ablation day)
Secondary outcomes (4)
Cumulative Incidence of 2-year Local Tumor Progression
A competing risk analysis was conducted to estimate the 2-year cumulative incidence of local tumor progression. Progression followed ablation reporting standards and RECIST v1.1 (mRECIST for HCC).
Measured: Time to local tumor progression (LTP) was measured from ablation to earliest LTP or death (competing event). Follow-up imaging continued up to 24 months.
Overall Survival
The Kaplan-Meier method was used to estimate overall survival
Measured: Overall survival was measured from the date of ablation to the date of death from any cause. Patients still alive were censored at the date of last clinic visit, with follow-up up to 24 months after ablation.
Intrahepatic Progression-free Survival (for the Randomized Group)
Competing risk analysis was conducted to estimate the 2-year intrahepatic (progression outside of ablation zone), considering the progression of the ablated tumor and treating death as a competing event.
Measured: Up to 2 years
Extrahepatic Progression-free Survival
Competing risk analysis was conducted to estimate the 2-year extrahepatic cumulative incidence of progression, considering the progression of the ablated tumor and treating death as a competing event.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start10 Jan 2020
- Primary completion31 Oct 2024
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant Liver NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- BRUNO C ODISIO, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083378
- Sponsor's protocol ID
- 2019-0213
- Other IDs
- NCI-2019-05762, 2019-0213
- Status last verified
- Sep 2026
- First submitted
- 5 Sep 2019
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Siddiqi NS, Albuquerque J, Paolucci I, Lin YM, O'Connor C, Haddad A, Jones AK, Vauthey JN, Brock KK, Odisio BC. Quantifying Functional Liver Volume Loss after CT-guided Percutaneous Thermal Ablation: A COVER-ALL Trial Post Hoc Analysis. Radiol Imaging Cancer. 2026 Mar;8(2):e250385. doi: 10.1148/rycan.250385.
PubMed 41823606Odisio BC, Albuquerque J, Lin YM, Anderson BM, O'Connor CS, Rigaud B, Briones-Dimayuga M, Jones AK, Fellman BM, Huang SY, Kuban J, Metwalli ZA, Sheth R, Habibollahi P, Patel M, Shah KY, Cox VL, Kang HC, Morris VK, Kopetz S, Javle MM, Kaseb A, Tzeng CW, Cao HT, Newhook T, Chun YS, Vauthey JN, Gupta S, Paolucci I, Brock KK. Software-based versus visual assessment of the minimal ablative margin in patients with liver tumours undergoing percutaneous thermal ablation (COVER-ALL): a randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2025 May;10(5):442-451. doi: 10.1016/S2468-1253(25)00024-X. Epub 2025 Mar 13.
PubMed 40090348Lin YM, Paolucci I, Anderson BM, O'Connor CS, Rigaud B, Briones-Dimayuga M, Jones KA, Brock KK, Fellman BM, Odisio BC. Study Protocol COVER-ALL: Clinical Impact of a Volumetric Image Method for Confirming Tumour Coverage with Ablation on Patients with Malignant Liver Lesions. Cardiovasc Intervent Radiol. 2022 Dec;45(12):1860-1867. doi: 10.1007/s00270-022-03255-3. Epub 2022 Sep 4.
PubMed 36058995