Child-Pugh Class APhase 3NCT02762266
Transarterial Chemoembolization Compared With Stereotactic Body Radiation Therapy or Stereotactic Ablative Radiation Therapy in Treating Patients With Residual or Recurrent Liver Cancer Undergone Initial Transarterial Chemoembolization
A Phase 3 study testing Stereotactic Body Radiation Therapy, Transarterial Chemoembolization and embolic agent in people with Child-Pugh Class A and Child-Pugh Class B, run by Stanford University at 2 sites in 2 countries.
Trial summary
This randomized phase III trial studies how well transarterial chemoembolization (TACE) works compared to stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR) in patients with liver cancer that remain after attempts to remove the cancer have been made (residual) or has come back… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Child-Pugh Class A, Child-Pugh Class B, Recurrent Hepatocellular Carcinoma
- What is being tested?
- Stereotactic Body Radiation Therapy, Transarterial Chemoembolization and embolic agent
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 27 Feb 2016to 31 Dec 2022
- Phase
- Phase 3
- 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
- Confirmed hepatocellular carcinoma (HCC) by one of the following:
- Histopathology
- One radiographic technique that confirms a lesion >= 1 cm with arterial hypervascularization with washout on delayed phase
- Radiographic evidence of persistent, progressive, or recurrent disease in an area previously treated with TACE and determined from 3 months after initial TACE; this evaluation should be within 6 weeks of date of study eligibility
- Unifocal liver tumors not to exceed 7.5 cm in greatest axial dimension; multifocal lesions will be restricted to lesions that can be treated within a single target volume within the same liver segment and to an aggregate of 10 cm as long as the dose constraints to normal tissue can be met
- Eastern Clinical Oncology Group (ECOG) performance status 0, 1 or 2
Show all 9Show fewer
- Patients with liver disease classified as Child Pugh class A or B, with score =< 9 ((within 4 weeks of treatment)
- Life expectancy >= 6 months
- Ability of the research subject or authorized legal representative to understand and have the willingness to sign a written informed consent document
Who cannot join
- Prior radiotherapy to the upper abdomen
- Prior radioembolization to the liver
- Prior radiofrequency ablation (RFA) to index lesion
- Liver transplant
- Active gastrointestinal bleed within 2 weeks of study enrollment
- Ascites refractory to medical therapy (mild to moderate ascites is allowed)
Show all 11Show fewer
- Women who are pregnant or breastfeeding
- Administration of chemotherapy within the last 1 month
- Extrahepatic metastases
- Participation in another concurrent treatment protocol
- Prior history of malignancy other than HCC, dermatologic basal cell or squamous cell carcinoma
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
Official title: International Randomized Study of Transarterial Chemoembolization (TACE) Versus Stereotactic Body Radiotherapy (SBRT) / Stereotactic Ablative Radiotherapy (SABR) for Residual or Recurrent Hepatocellular Carcinoma After Initial TACE
This randomized phase III trial studies how well transarterial chemoembolization (TACE) works compared to stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR) in patients with liver cancer that remain after attempts to remove the cancer have been made (residual) or has come back (recurrent). TACE is a minimally invasive, image-guided treatment procedure that uses a catheter to deliver both chemotherapy medication and embolization materials into the blood vessels that lead to the tumors. SBRT or SABR may be able to send radiation directly to the tumor and cause less damage to normal liver tissue. It is not yet known whether TACE is more effective than SBRT or SABR in treating patients with persistent or recurrent liver cancer who have undergone initial TACE.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the freedom from local progression (FFLP) of TACE versus (vs) SABR in patients with persistent hepatocellular carcinoma (HCC) after TACE.
SECONDARY OBJECTIVES:
- To determine the progression-free survival (PFS) of TACE vs SABR in patients with persistent HCC after initial TACE.
II. To determine the overall survival (OS) of TACE vs SABR for persistent HCC. III. To determine the toxicities associated with TACE or SABR for persistent HCC.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients undergo TACE.
ARM II: Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks.
After completion of study treatment, patients are followed up for 1-2 weeks, 1, 3, 6, 12, and 18 months, and every 6 months up to 3 years.
- Being tested
- Stereotactic Body Radiation Therapy, Transarterial Chemoembolization, embolic agent, lipiodol
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body Radiation TherapyRadiation
Also called SBRT
Undergo SBRT
Transarterial ChemoembolizationProcedure or surgery
Also called TACE
Undergo TACE
embolic agentDrug
. Acceptable embolic agents include:
- Gelatin sponge (gelfoam)
- Polyvinyl alcohol (PVA) particles
- Microspheres / Embolic beads
lipiodolDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm I (TACE) | Active comparator | Patients undergo TACE. Receives: Procedure: Transarterial Chemoembolization; Drug: embolic agent; Drug: lipiodol |
| Arm II (SBRT) | Experimental | Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks. Receives: Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Local Progression Event
Local progression event: occurring in the treated hepatic lesion.
Measured: Up to 12 months
Secondary outcomes (11)
Comparison of Median Freedom From Extra Hepatic Progression
The time to freedom from extra hepatic progression will be estimated by competing risk models with death as a competing risk. Risk factors such as tumor size and institution will be tested in a multivariate Cox regression model adjusting for the competing risks.
Measured: Up to 16 weeks
Median Extra Hepatic PFS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group
Extra hepatic PFS within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.
Measured: At 18 months
Median FFLP for Patients With Tumors Smaller Than 3 cm and With Tumors Greater Than 3 cm Per Treatment Group
FFLP within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.
Measured: At 18 months
Median OS
Overall survival will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula. Log rank tests will be used to compare treatment groups. Cox proportional hazard models will be used to estimate hazard ratios between treatment groups and to assess other risk factors, in particular the effect of tumor size and the impact of the different institutions.
Measured: Time from randomization until death from any cause, assessed up to 3 years
Median OS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group
Within each subgroup OS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula.
Measured: At 18 months
Number of Participants With Disease Progression or Death
Including local, regional, or distant progression events, or death. Local progression event: occurring in the treated tumor. Regional progression event: occurring in the same part of the body as the treated tumor. Distant progression event: occurring outside the region of the body where the treated tumor is located.
Measured: Randomization through 3 years
Number of Participants With Disease Progression or Death by Tumor Size (<= 3 cm and > 3 cm) Per Treatment Group
Including local, regional, or distant progression events, or death. Local progression event: occurring in the treated tumor. Regional progression event: occurring in the same part of the body as the treated tumor. Distant progression event: occurring outside the region of the body where the treated tumor is located.
Measured: Randomization through 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Freedom From Local Progression (FFLP)
The impact of elevated AFP level on time to event endpoints will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.
Measured: Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Progression-free Survival (PFS)
The impact of elevated AFP level on time to event endpoints will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.
Measured: Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Extra Hepatic PFS
The impact of elevated AFP level on time to event endpoints: FFLP, PFS, extra hepatic PFS and OS will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.
Measured: Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Overall Survival (OS)
The impact of elevated AFP level on time to event endpoints will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2016 (estimated)
- Study start27 Feb 2016
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Why it stopped: Business decision - funding
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 Child-Pugh Class AStudies of the same condition, open and under way.
- More trials run by Stanford 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Erqi Liu Pollom, Stanford University
- Investigators
- Erqi Liu Pollom, MD, Principal investigator, Stanford UniversityDaniel Chang, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02762266
- Sponsor's protocol ID
- IRB-35937
- Other IDs
- NCI-2016-00418, P30CA124435, HEP0052
- Status last verified
- Mar 2024
- First submitted
- 5 Apr 2016
- Last updated
- 12 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Randomized Study of Transarterial Chemoembolization (TACE) Versus Stereotactic Body Radiotherapy (SBRT) / Stereotactic Ablative Radiotherapy (SABR) for Residual or Recurrent Hepatocellular Carcinoma After Initial TACE
- ClinicalTrials.gov ID
- NCT02762266
- Acronym / sponsor ID
- IRB-35937
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision - funding
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 27 Feb 2016 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 4 May 2016 (estimated)
- Results
- Posted 12 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase III trial studies how well transarterial chemoembolization (TACE) works compared to stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR) in patients with liver cancer that remain after attempts to remove the cancer have been made (residual) or has come back (recurrent). TACE is a minimally invasive, image-guided treatment procedure that uses a catheter to deliver both chemotherapy medication and embolization materials into the blood vessels that lead to the tumors. SBRT or SABR may be able to send radiation directly to the tumor and cause less damage to normal liver tissue. It is not yet known whether TACE is more effective than SBRT or SABR in treating patients with persistent or recurrent liver cancer who have undergone initial TACE.
Detailed description
PRIMARY OBJECTIVES:
- To determine the freedom from local progression (FFLP) of TACE versus (vs) SABR in patients with persistent hepatocellular carcinoma (HCC) after TACE.
SECONDARY OBJECTIVES:
- To determine the progression-free survival (PFS) of TACE vs SABR in patients with persistent HCC after initial TACE.
II. To determine the overall survival (OS) of TACE vs SABR for persistent HCC. III. To determine the toxicities associated with TACE or SABR for persistent HCC.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients undergo TACE.
ARM II: Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks.
After completion of study treatment, patients are followed up for 1-2 weeks, 1, 3, 6, 12, and 18 months, and every 6 months up to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (TACE) | Active comparator | Procedure: Transarterial Chemoembolization, Drug: embolic agent, Drug: lipiodolPatients undergo TACE. |
| Arm II (SBRT) | Experimental | Radiation: Stereotactic Body Radiation TherapyBeginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Confirmed hepatocellular carcinoma (HCC) by one of the following:
- Radiographic evidence of persistent, progressive, or recurrent disease in an area previously treated with TACE and determined from 3 months after initial TACE; this evaluation should be within 6 weeks of date of study eligibility
- Unifocal liver tumors not to exceed 7.5 cm in greatest axial dimension; multifocal lesions will be restricted to lesions that can be treated within a single target volume within the same liver segment and to an aggregate of 10 cm as long as the dose constraints to normal tissue can be met
- Eastern Clinical Oncology Group (ECOG) performance status 0, 1 or 2
- Patients with liver disease classified as Child Pugh class A or B, with score =< 9 ((within 4 weeks of treatment)
Key exclusion criteria (11 listed)
- Prior radiotherapy to the upper abdomen
- Prior radioembolization to the liver
- Prior radiofrequency ablation (RFA) to index lesion
- Liver transplant
- Active gastrointestinal bleed within 2 weeks of study enrollment
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 |
|---|---|---|
| Stereotactic Body Radiation TherapyAlso: SBRTUndergo SBRT | Radiation | Arm II (SBRT) |
| Transarterial ChemoembolizationAlso: TACEUndergo TACE | Procedure or surgery | Arm I (TACE) |
| embolic agent. Acceptable embolic agents include: * Gelatin sponge (gelfoam) * Polyvinyl alcohol (PVA) particles * Microspheres / Embolic beads | Drug | Arm I (TACE) |
| lipiodol | Drug | Arm I (TACE) |
Primary outcome
Number of Participants With a Local Progression Event
Time frame: Up to 12 months
Local progression event: occurring in the treated hepatic lesion.
11 secondary outcomes
Comparison of Median Freedom From Extra Hepatic Progression
Time frame: Up to 16 weeks
Median Extra Hepatic PFS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group
Time frame: At 18 months
Median FFLP for Patients With Tumors Smaller Than 3 cm and With Tumors Greater Than 3 cm Per Treatment Group
Time frame: At 18 months
Median OS
Time frame: Time from randomization until death from any cause, assessed up to 3 years
Median OS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group
Time frame: At 18 months
Number of Participants With Disease Progression or Death
Time frame: Randomization through 3 years
Number of Participants With Disease Progression or Death by Tumor Size (<= 3 cm and > 3 cm) Per Treatment Group
Time frame: Randomization through 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Freedom From Local Progression (FFLP)
Time frame: Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Progression-free Survival (PFS)
Time frame: Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Extra Hepatic PFS
Time frame: Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Overall Survival (OS)
Time frame: Up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Erqi Liu Pollom, MD principal investigator
Stanford University
Daniel Chang, MD principal investigator
Stanford University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Stereotactic Body Radiation Therapy, Transarterial Chemoembolization and embolic agent in people with Child-Pugh Class A and Child-Pugh Class B, run by Stanford University at 2 sites in 2 countries.
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 9 inclusion and 11 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 12 Mar 2024. 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, Japan. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2024). 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?
Number of Participants With a Local Progression Event (time frame: Up to 12 months). 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 12 Mar 2024.