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Trial registered on ANZCTR


Registration number
ACTRN12617000030370
Ethics application status
Not required
Date submitted
14/12/2016
Date registered
9/01/2017
Date last updated
11/12/2018
Date data sharing statement initially provided
11/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Prospective Meta-analysis of Selective Internal Radiation Therapy (SIRT) versus Sorafenib for Hepatocellular Carcinoma
Scientific title
Individual Patient Data Prospective Meta-analysis (IPD PMA) of Selective Internal Radiation Therapy (SIRT) versus Sorafenib for Locally Advanced or Recurrent Hepatocellular Carcinoma (HCC) Including SARAH and SIRveNIB Trials
Secondary ID [1] 290690 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
VESPRO
Linked study record
Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC) (SIRveNIB) - NCT01135056
SorAfenib Versus RADIOEMBOLIZATION in Advanced Hepatocellular Carcinoma (SARAH) - NCT01482442

Health condition
Health condition(s) or problem(s) studied:
Patients with locally advanced HCC or recurrent HCC 301225 0
Condition category
Condition code
Cancer 300983 300983 0 0
Liver

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Selective Internal Radiation Therapy (SIRT) using SIR-Spheres yttrium-90 microspheres.
1. This is a retrospective meta-analysis using individual patient data from 2 trials that have completed recruitment.
2.
SorAfenib Versus RADIOEMBOLIZATION in Advanced Hepatocellular Carcinoma (SARAH) - NCT01482442 - December 2011 - April 2016
Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC) (SIRveNIB) - NCT01135056 - July 2010 - September 2016
Intervention code [1] 296570 0
Not applicable
Comparator / control treatment
Sorafenib (Continuous oral dose of 400mg, twice daily)
Control group
Active

Outcomes
Primary outcome [1] 300411 0
Overall survival - this outcome is assessed by review of SARAH and SIRveNIB trial data.
Timepoint [1] 300411 0
Time from randomisation until death from any cause or the end of the trial
Secondary outcome [1] 329896 0
Progression in the liver - this outcome is assessed by review of SARAH and SIRveNIB trial data.
Timepoint [1] 329896 0
Time from randomization until the first progression in the liver or the end of the trial
Secondary outcome [2] 329897 0
Progression free survival - this outcome is assessed by review of SARAH and SIRveNIB trial data.
Timepoint [2] 329897 0
Time from randomization until disease progression or death at the end of the trial
Secondary outcome [3] 329900 0
Tumour response rate - this outcome is assessed by review of SARAH and SIRveNIB trial data.
Timepoint [3] 329900 0
3 months from randomization until progression or the end of the trial
Secondary outcome [4] 329901 0
Disease control rate - this outcome is assessed by review of SARAH and SIRveNIB trial data.
Timepoint [4] 329901 0
3 months from randomization until progression or the end of the trial
Secondary outcome [5] 329902 0
Toxicities level this outcome is assessed by review of SARAH and SIRveNIB trial data.
Timepoint [5] 329902 0
Time from the start of treatment until 30 days from the last dose of Sorafenib or 6 months from the last dose of SIRT

Eligibility
Key inclusion criteria
*Adults (older than or equal to 18 years of age) with a life expectancy of over 3 months.
*Histologic or cytologic diagnosis or AASLD criteria for the diagnosis of HCC and at least one measurable lesion on CT according to RECIST criteria
*Written consent.
*Patients with advanced HCC according to the Barcelona criteria (stage C), with or without portal invasion, and who are not eligible for surgical resection, liver transplantation or radiofrequency (ablation) OR patients with recurrent HCC (new
location) or patients with chemoembolisation failure.
*ECOG performance status lesser or equal to 1.
*Liver cirrhosis Child-Pugh A - B7.

SIRveNIB only:
Adequate haematological, renal and hepatic function as follows*:
Leukocytes greater or equal to 2,500/µL
Platelets greater or equal to 80,000/µL
Haemoglobin greater than 9.5 g/dL
Total bilirubin lesser than 2.0 mg/dL
INR lesser or equal to 2.0
ALP lesser or equal to 5 x institutional upper limit of normal
AST and ALT lesser or equal to 5 x institutional upper limit of normal
Albumin greater or equal to 2.5 g/dL
Creatinine lesser or equal to 2.0 mg/dL

*Suitable for protocol treatment as determined by clinical assessment undertaken by the Investigator.
SARAH only:
*Neutrophils greater or equal to 1500/mm3.
*Platelets greater or equal to 50000/mm3.
*Haemoglobin greater or equal to 9 g/100 mL.
*Bilirubin lesser or equal to 50 µmol/L.
*INR lesser or equal to 1.5.
*AST or ALT lesser or equal to 5 x ULN.
*Adequate kidney function, creatinine lesser 150 µmol.

*Patient affiliated to social security scheme or beneficiary.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Advanced Liver disease with A Child-Pugh score > B7 or active digestive haemorrhage or encephalopathy or refractory ascites.
*Patient unable or unwilling to comply with the treatment and follow-up required by the trial.
*Previously treated advanced HCC (excluding chemoembolisation).
*Contraindication to hepatic artery catheterisation such as severe peripheral arterial disease precluding catheterisation.
*Allergy to contrast agents.
*Pregnant or breastfeeding women.
*Mental illness or Other psychological disorder affecting the informed consent.
SARAH only:
*Patient unable to take oral medication.
*Extrahepatic metastases (including pulmonary tumours > 1 cm and lymph node tumours > 2 cm).
*Other primary tumour except for basal-cell carcinomas or superficial bladder cancers.
SIRveNIB only:
*Complete obstruction of the main portal vein.
*Extrahepatic metastases except patients with small lung nodules or lymph nodes.
*Portal hypertension with hepatofugal flow as documented on baseline spiral CT scan.
*Male patients must be surgically sterile, or if sexually active and having a pre-menopausal female partner then must be using an acceptable form of contraception.

Study design
Purpose
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Analyses of the primary endpoint will be performed using the intention-to-treat (ITT) principal (patients analysed according to the treatment to which they were randomised). The primary outcome will be compared using the inverse-variance weighted hazard ratio of the individual trials. A sensitivity analysis using a stratified log-rank test and an unadjusted stratified proportional hazards model (stratified by trial) test will also be performed. The comparison will be one based on superiority. In the event that the 95% CI for the hazard ratio crosses the null, if the one-sided upper 95% CI for this hazard ratio does not breach the non-inferiority boundary of 1.10 then this will be interpreted as supporting evidence that the SIRT therapy is not appreciably worse than sorafenib. Analyses of secondary endpoints will be performed similar to the primary endpoint.

Subgroup analyses will be performed according to the following patients’ baseline characteristics:
*Age (<65 years, >=65 years),
*Gender (male, female)
*ECOG performance status (0,1)
*Tumour size (<= 50% of liver, > 50% of liver),
*Presence or absence of portal vein thrombosis,
*BCLC stage (B1 and B2, B3 and B4 and C; using Bolondi Criteria),
*Prior HCC treatment (yes, no),
*Hepatitis status (B, C, both),
*Unilobal versus bilobal disease,
*Single focal versus multifocal disease,
*Serum alpha-feto protein level (<=100 ng/ml, >100 ng/ml).

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
16/07/2010
Date of last participant enrolment
Anticipated
Actual
25/05/2016
Date of last data collection
Anticipated
31/12/2018
Actual
Sample size
Target
827
Accrual to date
Final
819
Recruitment outside Australia
Country [1] 8445 0
Myanmar
State/province [1] 8445 0
Country [2] 8446 0
Taiwan, Province Of China
State/province [2] 8446 0
Country [3] 8447 0
Thailand
State/province [3] 8447 0
Country [4] 8448 0
Mongolia
State/province [4] 8448 0
Country [5] 8449 0
Indonesia
State/province [5] 8449 0
Country [6] 8450 0
Philippines
State/province [6] 8450 0
Country [7] 8451 0
Hong Kong
State/province [7] 8451 0
Country [8] 8452 0
New Zealand
State/province [8] 8452 0
Country [9] 8453 0
Brunei Darussalam
State/province [9] 8453 0
Country [10] 8454 0
France
State/province [10] 8454 0
Country [11] 8459 0
Malaysia
State/province [11] 8459 0
Country [12] 8460 0
Korea, Republic Of
State/province [12] 8460 0

Funding & Sponsors
Funding source category [1] 295114 0
Government body
Name [1] 295114 0
National Medical Research Council
Country [1] 295114 0
Singapore
Funding source category [2] 295115 0
Commercial sector/Industry
Name [2] 295115 0
Sirtex Medical Limited
Country [2] 295115 0
Australia
Primary sponsor type
Hospital
Name
National Cancer Centre Singapore
Address
11 Hospital Drive Singapore 169610
Country
Singapore
Secondary sponsor category [1] 293934 0
Hospital
Name [1] 293934 0
Assistance Publique - Hopitaux de Paris
Address [1] 293934 0
3 Avenue Victoria, 75004 Paris, France
Country [1] 293934 0
France
Other collaborator category [1] 279340 0
University
Name [1] 279340 0
NHMRC Clinical Trials Centre, University of Sydney
Address [1] 279340 0
Camperdown NSW 2006, Australia
Country [1] 279340 0
Australia
Other collaborator category [2] 279341 0
Other
Name [2] 279341 0
Singapore Clinical Research Institute
Address [2] 279341 0
31 Biopolis Way, Singapore 138669
Country [2] 279341 0
Singapore

Ethics approval
Ethics application status
Not required

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1288 1288 0 0
/AnzctrAttachments/371973-Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced HCC-study protocol for a phase iii randomized controlled trial.pdf (Publication)
Attachments [2] 1289 1289 0 0
/AnzctrAttachments/371973-SARAH Study protocol for a randomised controlled trial.pdf (Publication)

Contacts
Principal investigator
Name 70950 0
Prof Pierce Chow
Address 70950 0
National Cancer Centre of Singapore
11 Hospital Drive Singapore 169610
Country 70950 0
Singapore
Phone 70950 0
+6565762151
Fax 70950 0
+6562257559
Email 70950 0
[email protected]
Contact person for public queries
Name 70951 0
Pierce Chow
Address 70951 0
National Cancer Centre of Singapore
11 Hospital Drive Singapore 169610
Country 70951 0
Singapore
Phone 70951 0
+6565762151
Fax 70951 0
+6562257559
Email 70951 0
[email protected]
Contact person for scientific queries
Name 70952 0
Pierce Chow
Address 70952 0
National Cancer Centre of Singapore
11 Hospital Drive Singapore 169610
Country 70952 0
Singapore
Phone 70952 0
+6565762151
Fax 70952 0
+6562257559
Email 70952 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will be analysed as a group.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIVESPRO: An Individual Patient Data Prospective Meta-Analysis of Selective Internal Radiation Therapy Versus Sorafenib for Advanced, Locally Advanced, or Recurrent Hepatocellular Carcinoma of the SARAH and SIRveNIB Trials2017https://doi.org/10.2196/resprot.7016
N.B. These documents automatically identified may not have been verified by the study sponsor.