Hepatocellular CarcinomaPROVE-HCCNCT03402607
Trial Comparing PLA to HIGRT (PROVE-HCC)
A study testing Percutaneous Local Ablation and Hypofractionated Image Guided Radiation Therapy in people with Hepatocellular Carcinoma, run by Duke University at 2 sites in United States.
Trial summary
This phase II, randomized trial compare Quality of Life for patients with Hepatocellular Carcinoma (HCC) who are not surgical candidates or decline surgery and are treated with Percutaneous Local Ablation (PLA) or Hypofractionated Image-Guided Radiation Therapy (HIGRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Percutaneous Local Ablation and Hypofractionated Image Guided Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Aug 2018to 25 Mar 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- HCC diagnosed either by histology/pathology or Liver Imaging Reporting and Data System (LIRADs 5 per the ACR's LIRADs criteria) by CT or MRI
- Patient is 18 years or older
- ECOG Performance status of 0-2
- Child Pugh score A5, A6, B7 or B8
- Lesions less than or equal to 5cm in size
- Less than or equal to 3 lesions in the liver to be treated on protocol
- Lesion amenable to treatment with both PLA and HIGRT; for PLA treatment this requires the lesion be visible via ultrasound and/or non-contrast CT or feasible per treating physician
Who cannot join
- Child Pugh score B9 or Class C
- Fluctuating ascites
- Inability to complete baseline QOL forms
- Concurrent administration of systemic therapy for HCC
- Prior liver RT is an exclusion unless subject participation is approved by the PI
- Positive serum pregnancy test
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Durham Veterans Administration Medical Center (DVAMC)
Durham, North Carolina, 27705
Duke Cancer Center
Durham, North Carolina, 27710
About this study
Official title: Phase II Randomized Trial Comparing Percutaneous Ablation to Hypofractionated Image-Guided Radiation Therapy in Veteran and Non-Veteran, Non-surgical Hepatocellular Carcinoma Patients (PROVE-HCC)
This phase II, randomized trial compare Quality of Life for patients with Hepatocellular Carcinoma (HCC) who are not surgical candidates or decline surgery and are treated with Percutaneous Local Ablation (PLA) or Hypofractionated Image-Guided Radiation Therapy (HIGRT).
Read the detailed description
Administrative clarification:
This clinical trial was terminated due to poor enrollment and was replaced by a separate non-randomized trial (NCT04933435).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Percutaneous Local Ablation, Hypofractionated Image Guided Radiation Therapy
- Keywords
- Unresectable
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Percutaneous Local AblationProcedure or surgery
Also called Microwave Ablation (MWA)
Microwave Ablation (MWA) is a form of percutaneous localized ablation using thermal ablation techniques to treat cancer via direct coagulative necrosis. Microwaves can generate high temperatures in a short period of time; MWA has the potential to improve treatment efficacy over radiofrequency ablation as it can be used to treat larger lesions and has less susceptibility to heat-sink due to vessel proximity. MWA uses electromagnetic waves (300 MHz to 300 GHz) to produce oscillation of polar molecules within tissue; this generates tissue necrosis through frictional heating. For HCC, one or more microwave antennae are inserted into the liver, usually under the guidance of ultrasonography or computed tomography (CT). Frequency and length of treatment is determined on a case by case basis depending on tumor size and proximity to vessels or other organs at risk.
Hypofractionated Image Guided Radiation TherapyRadiation
Also called HIGRT
HIGRT represents the only non-invasive curative modality in the management of HCC. HCC patients typically have a host of other medical comorbidities complicated by underlying liver dysfunction that makes the implementation of liver-directed therapy challenging. Presently HIGRT is typically offered only after alternative surgical (transplantation/hepatectomy) and non-operative approaches (PLA/embolization) have been exhausted.
| Study group | Role | What they receive |
|---|---|---|
| Percutaneous Local Ablation (PLA) | Active comparator | A PLA procedure uses high-energy radio waves to treat liver tumors. Using CT and ultrasound guidance the doctor inserts a thin, needle-like probe into the liver tumor A high-frequency current is then passed through the tip of the probe, which heats the tumor with the goal to destroy the cancer cells. This may be done as an outpatient procedure or a short (1-2 day) hospital stay. PLA is the standard treatment for patients with liver cancer who cannot undergo liver surgery. Receives: Procedure: Percutaneous Local Ablation |
| Hypofractionated Image-Guided Radiation Therapy (HIGRT) | Active comparator | HIGRT is an emerging treatment option for patients with HCC; it utilizes external radiation where multiple beams enter the body from multiple angles to treat the liver cancer over typically 5-10 treatments while minimizing radiation to normal tissues. You will receive between 5-10 fractions (treatments) of radiation. Fraction size will be either 5 or 10 Gy (pronounced Gray, a standard unit of radiation measurement) depending on your tumor size and location or underlying liver function. The total dose of radiation is 50 Gy. Receives: Radiation: Hypofractionated Image Guided Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Quality of Life (QOL) Using EORTC C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30)
To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT. The EORTC QLQ-C30 reports a Summary Score that is calculated from the mean of 13 of the 15 QLQ-C30 scales (excluding Global Quality of Life scale and the Financial Impact scale). 28 of the items have a range of 1 (not at all) to 4 (very much) and two of them have a range of 1 (very poor) to 7 (excellent). The total summary score ranges from 30 to 126, with lower scores indicating a better quality of life. Only the change in summary score is reported; no individual subscale scores are reported.
Measured: Baseline to one month
Secondary outcomes (5)
Change in Quality of Life (QOL) Using The Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Assessment
To compare change in Quality of Life (QOL), as measured by the FACT-Hep questionnaire post treatment in patients receiving PLA vs HIGRT from baseline to 1 month. The FACT-Hep Scale consists of five subscales: Physical well-being (PWB), Social/Family well-being (SWB), Emotional well-being (EWB), Functional well-being (FWB), and the Hepatobiliary Cancer Subscale (HCS). Total score ranges from 0 to 180, with higher scores indicating better quality of life. Average differences in each FACT-Hep Total Score for 3 months minus baseline are reported by treatment arm; no individual subscales are reported. An average difference > 0 indicates improvement in QOL at 3 versus baseline. An average difference < 0 indicates a worsening of QOL at 1 month versus baseline.
Measured: Baseline, 1 month, 3 months; change between baseline and 3 months reported
Change in Quality of Life (QOL) Using EORTC QLQ C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30)
To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT. The EORTC QLQ-C30 reports a Summary Score that is calculated from the mean of 13 of the 15 QLQ-C30 scales (excluding Global Quality of Life scale and the Financial Impact scale). 28 of the items have a range of 1 (not at all) to 4 (very much) and two of them have a range of 1 (very poor) to 7 (excellent). The total summary score ranges from 30 to 126, with lower scores indicating a better quality of life. Only the change in summary score is reported; no individual subscale scores are reported.
Measured: Baseline to 3 months
Change in Quality of Life (QOL) Using EORTC QLQ C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30)
To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT. To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT. The EORTC QLQ-C30 reports a Summary Score that is calculated from the mean of 13 of the 15 QLQ-C30 scales (excluding Global Quality of Life scale and the Financial Impact scale). 28 of the items have a range of 1 (not at all) to 4 (very much) and two of them have a range of 1 (very poor) to 7 (excellent). The total summary score ranges from 30 to 126, with lower scores indicating a better quality of life. Only the change in summary score is reported; no individual subscale scores are reported.
Measured: Baseline to 6 months
Number of Participants With Grade 2 or Higher Adverse Events
Grade ≥2 acute toxicity within 90 days of treatment initiation for each treatment as defined by the CTCAE v4.0
Measured: Up to 90 days post treatment
The Total Healthcare System Costs Associated With PLA vs HIGRT
Healthcare system costs estimated based on national averages for billable charges for all codes associated with PLA vs HIRGT throughout the course of treatment through 90 days post treatment.
Measured: From time of intervention to 90 days post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2018
- Study start8 Aug 2018
- Primary completion25 Jul 2019
- Study completion25 Mar 2020
Why it stopped: Lack of enrollment
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.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Durham VA Medical Center, Hunter Holmes McGuire VA Medical Center
- Responsible party
- Sponsor
- Investigators
- Manisha Palta, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03402607
- Sponsor's protocol ID
- Pro00089525
- Acronym
- PROVE-HCC
- Status last verified
- Jul 2022
- First submitted
- 11 Jan 2018
- Last updated
- 8 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Trial Comparing Percutaneous Ablation to Hypofractionated Image-Guided Radiation Therapy in Veteran and Non-Veteran, Non-surgical Hepatocellular Carcinoma Patients (PROVE-HCC)
- ClinicalTrials.gov ID
- NCT03402607
- Acronym / sponsor ID
- PROVE-HCC / Pro00089525
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Unresectable
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Durham VA Medical Center, Hunter Holmes McGuire VA Medical Center
- Study start
- 8 Aug 2018 (actual)
- Primary completion
- 25 Jul 2019 (actual)
- Study completion
- 25 Mar 2020 (actual)
- First posted
- 18 Jan 2018 (actual)
- Results
- Posted 6 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II, randomized trial compare Quality of Life for patients with Hepatocellular Carcinoma (HCC) who are not surgical candidates or decline surgery and are treated with Percutaneous Local Ablation (PLA) or Hypofractionated Image-Guided Radiation Therapy (HIGRT).
Detailed description
Administrative clarification:
This clinical trial was terminated due to poor enrollment and was replaced by a separate non-randomized trial (NCT04933435).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Percutaneous Local Ablation (PLA) | Active comparator | Procedure: Percutaneous Local AblationA PLA procedure uses high-energy radio waves to treat liver tumors. Using CT and ultrasound guidance the doctor inserts a thin, needle-like probe into the liver tumor A high-frequency current is then passed through the tip of the probe, which heats the tumor with the goal to destroy the cancer cells. This may be done as an outpatient procedure or a short (1-2 day) hospital stay. PLA is the standard treatment for patients with liver cancer who cannot undergo liver surgery. |
| Hypofractionated Image-Guided Radiation Therapy (HIGRT) | Active comparator | Radiation: Hypofractionated Image Guided Radiation TherapyHIGRT is an emerging treatment option for patients with HCC; it utilizes external radiation where multiple beams enter the body from multiple angles to treat the liver cancer over typically 5-10 treatments while minimizing radiation to normal tissues. You will receive between 5-10 fractions (treatments) of radiation. Fraction size will be either 5 or 10 Gy (pronounced Gray, a standard unit of radiation measurement) depending on your tumor size and location or underlying liver function. The total dose of radiation is 50 Gy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- HCC diagnosed either by histology/pathology or Liver Imaging Reporting and Data System (LIRADs 5 per the ACR's LIRADs criteria) by CT or MRI
- Patient is 18 years or older
- ECOG Performance status of 0-2
- Child Pugh score A5, A6, B7 or B8
- Lesions less than or equal to 5cm in size
Key exclusion criteria (6 listed)
- Child Pugh score B9 or Class C
- Fluctuating ascites
- Inability to complete baseline QOL forms
- Concurrent administration of systemic therapy for HCC
- Prior liver RT is an exclusion unless subject participation is approved by the PI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Percutaneous Local AblationAlso: Microwave Ablation (MWA)Microwave Ablation (MWA) is a form of percutaneous localized ablation using thermal ablation techniques to treat cancer via direct coagulative necrosis. Microwaves can generate high temperatures in a short period of time; MWA has the potential to improve treatment efficacy over radiofrequency ablation as it can be used to treat larger lesions and has less susceptibility to heat-sink due to vessel proximity. MWA uses electromagnetic waves (300 MHz to 300 GHz) to produce oscillation of polar molecules within tissue; this generates tissue necrosis through frictional heating. For HCC, one or more microwave antennae are inserted into the liver, usually under the guidance of ultrasonography or computed tomography (CT). Frequency and length of treatment is determined on a case by case basis depending on tumor size and proximity to vessels or other organs at risk. | Procedure or surgery | Percutaneous Local Ablation (PLA) |
| Hypofractionated Image Guided Radiation TherapyAlso: HIGRTHIGRT represents the only non-invasive curative modality in the management of HCC. HCC patients typically have a host of other medical comorbidities complicated by underlying liver dysfunction that makes the implementation of liver-directed therapy challenging. Presently HIGRT is typically offered only after alternative surgical (transplantation/hepatectomy) and non-operative approaches (PLA/embolization) have been exhausted. | Radiation | Hypofractionated Image-Guided Radiation Therapy (HIGRT) |
Primary outcome
Change in Quality of Life (QOL) Using EORTC C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30)
Time frame: Baseline to one month
To compare change in Quality of Life (QOL), as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30) post treatment in patients receiving PLA vs HIGRT. The EORTC QLQ-C30 reports a Summary Score that is calculated from the mean of 13 of the 15 QLQ-C30 scales (excluding Global Quality of Life scale and the Financial Impact scale). 28 of the items have a range of 1 (not at all) to 4 (very much) and two of them have a range of 1 (very poor) to 7 (excellent). The total summary score ranges from 30 to 126, with lower scores indicating a better quality of life. Only the change in summary score is reported; no individual subscale scores are reported.
5 secondary outcomes
Change in Quality of Life (QOL) Using The Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Assessment
Time frame: Baseline, 1 month, 3 months; change between baseline and 3 months reported
Change in Quality of Life (QOL) Using EORTC QLQ C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30)
Time frame: Baseline to 3 months
Change in Quality of Life (QOL) Using EORTC QLQ C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30)
Time frame: Baseline to 6 months
Number of Participants With Grade 2 or Higher Adverse Events
Time frame: Up to 90 days post treatment
The Total Healthcare System Costs Associated With PLA vs HIGRT
Time frame: From time of intervention to 90 days post treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manisha Palta, MD principal investigator
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Percutaneous Local Ablation and Hypofractionated Image Guided Radiation Therapy in people with Hepatocellular Carcinoma, run by Duke University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Quality of Life (QOL) Using EORTC C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30) (time frame: Baseline to one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2022.