Liver CancerPhase 2NCT00956930
Chemoembolization Versus Radioembolization in Treating Patients With Liver Cancer That Cannot Be Treated With Radiofrequency Ablation Or Surgery
A Phase 2 study testing yttrium Y 90 glass microspheres and Doxorubicin in people with Liver Cancer, run by Northwestern University at 1 site in United States.
Trial summary
RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Radioembolization kills tumor cells by blocking the blood flow to the tumor and keeping radioactive substances near the tumor. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Liver Cancer
- What is being tested?
- yttrium Y 90 glass microspheres and Doxorubicin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to 15 Jul 2016
- Phase
- Phase 2
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults > 18 years old of either gender
- Diagnosis of liver confined HCC confirmed by histology or American Association for the Study of Liver Diseases (AASLD) guidelines [59,60] [appendix A].
- Lesions < 1 cm in diameter have a low likelihood of being malignant and should be followed. Lack of growth over 1-2 years suggests it is not HCC.
- AFP >200 and radiological evidence (arterial hypervascularity) of lesion > 2 cm does not require biopsy.
- Two imaging modalities (triphasic CT, MRI, ultrasound, angiography) demonstrating "arterial hypervascularity" in the background of cirrhosis does not require biopsy
- One imaging modality with a lesion with arterial hypervascularity with wash out in early or delayed venous phase, does not require a biopsy
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- Atypical appearances on imaging requires a biopsy.
- Non-conclusive biopsy requires closer monitoring
- For non-cirrhotics (by biopsy or imaging findings), diagnosis of HCC requires biopsy
- Patients with <50% liver involvement
- Measurable liver confined disease with bi-dimensional measurements, required within 4 weeks of screening. Lesions reported on imaging as "too small to characterize", abdominal lymph nodes < 2.0 cm or ascites in the setting of cirrhosis are not considered metastatic disease unless cytology proven.
- No segmental, lobar or main portal vein thrombosis as evidence by cross sectional imaging
- Prior resection permitted, no prior systemic, ablative or infusion therapy permitted
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 [appendix B]
- Childs score of A or B [appendix C]
- Required lab parameters within 28 days of screening
- Serum bilirubin ≤ 2.0 mg/dl (unless segmental infusion can be performed
- AST and ALT ≤ 5 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN
- Prothrombin time (PT)/ International normalized ratio (INR) ≤ 2.3 or PT ≤ 6 seconds above control. If subjects are being anticoagulated they can participate if proof of no coagulation abnormality existed prior to use of anticoagulants
- Negative serum or urine pregnancy test for females of child bearing potential
- Ability to understand and sign the informed consent; patient must have signed informed consent prior to registration on study
- Women of childbearing potential and sexually active males must use contraception while on study
- Lesions must be treatable angiographically by either radioembolization or chemoembolization.
Who cannot join
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Patients with infiltrative HCC are not eligible.
- Patients with bulk disease (≥70% tumor replacement of liver) are not eligible.
- Patients with ≥50% tumor replacement of liver, with an albumin < 3.0 g/dl are not eligible.
- Major surgery within 4 weeks prior to the screening visit
- Active clinically serious infection > Common Toxicity Criteria for Adverse Events (CTCAE v 4.0) Grade 2
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- Any condition (psychological, physical or use/abuse of substances) which, in the opinion of the principal investigator (PI) or a sub-investigator (sub-I), would possibly endanger the subject during their participation in the study, or allow for non-compliance with the investigational drug and treatment under study.
- Due to the experimental nature of the therapy and the unknown risk to a fetus, pregnant and/or lactating women are not eligible to participate in this study.
- In the opinion of the investigator, patient is not a candidate/lesion not amenable for RFA (e.g. lesion location, shape, abnormal coagulation parameters, multi-focality).
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University, Northwestern Memorial Hospital
Chicago, Illinois, 60611-3013
About this study
Official title: An Investigator Initiated Multicenter Prospective Randomized Study of Chemoembolization Versus Radioembolization for the Treatment of Hepatocellular Carcinoma (PREMIERE Trial)
RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Radioembolization kills tumor cells by blocking the blood flow to the tumor and keeping radioactive substances near the tumor. It is not yet known which treatment regimen is more effective in treating patients with liver cancer.
PURPOSE: This randomized phase II trial is studying radioembolization to see how well it works compared with chemoembolization in treating patients with liver cancer that cannot be treated with Radiofrequency Ablation or removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- Compare and contrast TACE and Y90 in order to determine either equivalence or superiority as measured by time-to-progression.
Secondary
- Characterize the safety and toxicity profile of these regimens.
- Determine the need for subsequent treatment in these patients.
- Determine tumor response in these patients
- Characterize change in quality of life and functional status in these patients.
- Determine time to progression in these patients.
OUTLINE: Patients are randomized to receive either TACE or Y90
- Arm I (radioembolization): Patients undergo radioembolization with yttrium Y 90 glass microspheres by hepatic artery infusion for approximately 1-3 courses.
- Arm II (transarterial chemoembolization [TACE]): Patients undergo TACE with mitomycin C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for approximately 1-3 courses.
- In both arms, treatment modifications may apply according to response.
After completion of study treatment, patients are followed every 3 months.
- Conditions
- Liver Cancer
- Being tested
- yttrium Y 90 glass microspheres, Doxorubicin
- Keywords
- advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
yttrium Y 90 glass microspheresRadiation
Also called Radioembolization
Patients undergo radioembolization.
DoxorubicinDrug
Also called Doxorubicin hydrocholoride, Adriamycin, Chemoembolization (TACE)
75mg fixed dose
| Study group | Role | What they receive |
|---|---|---|
| Arm I (radioembolization) | Experimental | Patients undergo radioembolization with yttrium Y 90 glass microspheres by hepatic artery infusion for approximately 1-3 courses. Receives: Radiation: yttrium Y 90 glass microspheres |
| Arm II (transarterial chemoembolization [TACE]) | Experimental | Patients undergo TACE with mitomycin C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for approximately 1-3 courses. Receives: Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (TTP) in Patients Treated With TACE and Y90
Compare and contrast TACE and Y90 in order to determine either equivalence or superiority as measured by time-to-progression. Patients have repeat imaging done (MRI or CT) at 1-month post procedure and then every 3 months after that. TTP and overall survival (OS) analyses were calculated from day of randomization by Kaplan-Meier analysis on intention-to-treat (ITT) basis.
Progression (which is detected on follow-up imaging scans) was defined as:
- Progression by World Health Organization (WHO) response criteria 25% increase in bidimensional cross product.
- Progression by European Assosciation for the Study of the Liver (EASL): 25% increase in arterial enhancement
- Malignant portal vein tumor thrombus development
- Index lesion: lesions requiring re-treatment because of worsening circumferential enhancement
- Development of new lesions or extra-hepatic metastases.
Measured: Up to 6 yrs
Secondary outcomes (2)
Number of Patients Who Achieved Complete or Partial Radiologic Response After Treatment
Repeat imaging (CT/MRI) and lab work including tumor markers will be assessed 1 month post-treatment then every 3 months after that. Both EASL \& WHO criteria are used.
By EASL criteria Complete response is 100% Decrease in amount of enhancing tissue in index lesion, Partial response is ≥50% deecrease in amount of enhancing tissue in index lesion, Stable disease is <50% Decrease in to ≤ 25% increase in amount of enhancing tissue in index lesion, Progressive disease <25% Increase in amount of enhancing tissue in index lesion and/or new enhancement in previously treated index lesion.
Measured: up to 6 years
Overall Survival
Comparing overall survival of both treatment arms.
Measured: From day of randomization until date of death, or liver transplant or 7/15/2016, whichever came first, assessed up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2009 (estimated)
- Study startAug 2009
- Primary completion2 Jun 2016
- Study completion15 Jul 2016
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 (1)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by Northwestern 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Riad Salem, Northwestern University
- Investigators
- Riad Salem, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00956930
- Sponsor's protocol ID
- STU 12339
- Other IDs
- P30CA060553, STU# 00012339, CDR0000651416
- Status last verified
- Nov 2022
- First submitted
- 8 Aug 2009
- Last updated
- 21 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Data will be published in medical journals.
Publications
Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller FH, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB, Rademaker A, Ganger D, Kulik L, Lewandowski RJ. Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. Gastroenterology. 2016 Dec;151(6):1155-1163.e2. doi: 10.1053/j.gastro.2016.08.029. Epub 2016 Aug 27.
PubMed 27575820
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator Initiated Multicenter Prospective Randomized Study of Chemoembolization Versus Radioembolization for the Treatment of Hepatocellular Carcinoma (PREMIERE Trial)
- ClinicalTrials.gov ID
- NCT00956930
- Acronym / sponsor ID
- STU 12339
- Conditions
- Liver Cancer
- Keywords
- advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2009
- Primary completion
- 2 Jun 2016 (actual)
- Study completion
- 15 Jul 2016 (actual)
- First posted
- 11 Aug 2009 (estimated)
- Results
- Posted 1 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Radioembolization kills tumor cells by blocking the blood flow to the tumor and keeping radioactive substances near the tumor. It is not yet known which treatment regimen is more effective in treating patients with liver cancer.
PURPOSE: This randomized phase II trial is studying radioembolization to see how well it works compared with chemoembolization in treating patients with liver cancer that cannot be treated with Radiofrequency Ablation or removed by surgery.
Detailed description
OBJECTIVES:
Primary
- Compare and contrast TACE and Y90 in order to determine either equivalence or superiority as measured by time-to-progression.
Secondary
- Characterize the safety and toxicity profile of these regimens.
- Determine the need for subsequent treatment in these patients.
- Determine tumor response in these patients
- Characterize change in quality of life and functional status in these patients.
- Determine time to progression in these patients.
OUTLINE: Patients are randomized to receive either TACE or Y90
- Arm I (radioembolization): Patients undergo radioembolization with yttrium Y 90 glass microspheres by hepatic artery infusion for approximately 1-3 courses.
- Arm II (transarterial chemoembolization [TACE]): Patients undergo TACE with mitomycin C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for approximately 1-3 courses.
- In both arms, treatment modifications may apply according to response.
After completion of study treatment, patients are followed every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (radioembolization) | Experimental | Radiation: yttrium Y 90 glass microspheresPatients undergo radioembolization with yttrium Y 90 glass microspheres by hepatic artery infusion for approximately 1-3 courses. |
| Arm II (transarterial chemoembolization [TACE]) | Experimental | Drug: DoxorubicinPatients undergo TACE with mitomycin C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for approximately 1-3 courses. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Adults > 18 years old of either gender
- Diagnosis of liver confined HCC confirmed by histology or American Association for the Study of Liver Diseases (AASLD) guidelines [59,60] [appendix A].
- Lesions < 1 cm in diameter have a low likelihood of being malignant and should be followed. Lack of growth over 1-2 years suggests it is not HCC.
- AFP >200 and radiological evidence (arterial hypervascularity) of lesion > 2 cm does not require biopsy.
- Two imaging modalities (triphasic CT, MRI, ultrasound, angiography) demonstrating "arterial hypervascularity" in the background of cirrhosis does not require biopsy
Key exclusion criteria (9 listed)
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Patients with infiltrative HCC are not eligible.
- Patients with bulk disease (≥70% tumor replacement of liver) are not eligible.
- Patients with ≥50% tumor replacement of liver, with an albumin < 3.0 g/dl are not eligible.
- Major surgery within 4 weeks prior to the screening visit
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 |
|---|---|---|
| yttrium Y 90 glass microspheresAlso: RadioembolizationPatients undergo radioembolization. | Radiation | Arm I (radioembolization) |
| DoxorubicinAlso: Doxorubicin hydrocholoride, Adriamycin, Chemoembolization (TACE)75mg fixed dose | Drug | Arm II (transarterial chemoembolization [TACE]) |
Primary outcome
Time to Progression (TTP) in Patients Treated With TACE and Y90
Time frame: Up to 6 yrs
Compare and contrast TACE and Y90 in order to determine either equivalence or superiority as measured by time-to-progression. Patients have repeat imaging done (MRI or CT) at 1-month post procedure and then every 3 months after that. TTP and overall survival (OS) analyses were calculated from day of randomization by Kaplan-Meier analysis on intention-to-treat (ITT) basis. Progression (which is detected on follow-up imaging scans) was defined as: 1. Progression by World Health Organization (WHO) response criteria 25% increase in bidimensional cross product. 2. Progression by European Assosciation for the Study of the Liver (EASL): 25% increase in arterial enhancement 3. Malignant portal vein tumor thrombus development 4. Index lesion: lesions requiring re-treatment because of worsening circumferential enhancement 5. Development of new lesions or extra-hepatic metastases.
2 secondary outcomes
Number of Patients Who Achieved Complete or Partial Radiologic Response After Treatment
Time frame: up to 6 years
Overall Survival
Time frame: From day of randomization until date of death, or liver transplant or 7/15/2016, whichever came first, assessed up to 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27575820Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller FH, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB, Rademaker A, Ganger D, Kulik L, Lewandowski RJ. Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. Gastroenterology. 2016 Dec;151(6):1155-1163.e2. doi: 10.1053/j.gastro.2016.08.029. Epub 2016 Aug 27.
- Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular CarcinomaLink provided by the sponsor.
- Individual participant dataSharing planned: No. Data will be published in medical journals.
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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.
Riad Salem, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing yttrium Y 90 glass microspheres and Doxorubicin in people with Liver Cancer, run by Northwestern University at 1 site 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 24 inclusion and 9 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: finished, as of the sponsor's last update on 21 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 1 Oct 2019). 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?
Time to Progression (TTP) in Patients Treated With TACE and Y90 (time frame: Up to 6 yrs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00956930, which also lists 1 linked publication.
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 21 Nov 2022.