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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01135056




Registration number
NCT01135056
Ethics application status
Date submitted
24/05/2010
Date registered
2/06/2010
Date last updated
24/04/2018

Titles & IDs
Public title
Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC)
Scientific title
Phase III Multi-Centre Open-Label Randomized Controlled Trial of Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (SIRveNIB)
Secondary ID [1] 0 0
AHCC06
Universal Trial Number (UTN)
Trial acronym
SIRveNIB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - SIR-Spheres
Treatment: Drugs - Sorafenib tosylate

Active Comparator: Sorafenib, Multikinase Inhibitor, Tablet - Sorafenib tosylate:
Sorafenib is a multikinase inhibitor that decreases tumor cell proliferation.
Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT- 3, RET, VEGFR-1, VEGFR- 2, VEGFR- 3, and PDGFR- ß). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. Sorafenib inhibited tumor growth of the human hepatocellular carcinoma and renal cell carcinoma, and several other human tumor xenografts in immunocompromised mice. A reduction in tumor angiogenesis and increases in tumor apoptosis was seen in models of human hepatocellular and renal cell carcinoma. Additionally a reduction in tumor cell signaling was seen in a model of human hepatocellular carcinoma.

Active Comparator: SIR-Spheres, Microspheres, Device - SIR-Spheres:
SIR-Spheres consist of biocompatible resin microspheres containing yttrium-90, with a size between 20 and 60 microns in diameter. Yttrium-90 is a high-energy pure beta-emitting isotope with no primary gamma emission. The half life of yttrium-90 is 64.1 hours. In clinical use which requires the isotope to decay to infinity, 94% of the radiation is delivered in 11 days leaving only background radiation with no therapeutic value.
SIR-Spheres is implanted into hepatic tumours by delivery via either the common hepatic artery or the right or left hepatic artery using a catheter or implanted port . Once SIR-Spheres is implanted into the liver, it is not metabolised or excreted and it stays permanently in the liver.


Treatment: Devices: SIR-Spheres
One time treatment. Dose administered based on tumour volume. Each vial is 3.0GBq.

Treatment: Drugs: Sorafenib tosylate
Oral Tablet, 400mg B.i.d, until progression or unacceptable toxicity develops

Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival - Overall Survival is defined as the time from the date of randomisation to the date of death due to any cause. All patients will be followed up until death to compare the overall survival between the two treatments. 2 years is an estimated time frame.
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Progression free survival in the liver - Progression-free survival in the liver is defined as the time interval between randomisation and the date of tumour progression in the liver or death, whichever is earlier. Tumour progression in the liver will be determined from serial CT scans. Diagnosis of tumour progression of disease should be made using the RECIST guideline version 1.1. 2 years is an estimated time frame.
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Progression free survival overall - Progression-free survival overall is defined as the time interval between randomisation and the date of tumour progression at any site in the body or death, whichever is earlier. Tumour progression at any site in the body will be measured by any definitive imaging technique including CT scan, MRI study or other nuclear medicine scan. The Investigator should clearly indicate the site of tumour progression (hepatic or extra-hepatic) at the time of recurrence.
2 years is an estimated time frame.
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Tumour Response Rate - Tumour response and progression will be evaluated in this study using the new response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [European Journal of Cancer (45): 228 - 247, 2009] (http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf).
2 years is an estimated time frame
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Toxicity and Safety - Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria (NCI-CTC) version 4.02. Patients for both treatment arms will be followed-up for safety and toxicity from the time of study entry (randomisation day) until 30 days post study conclusion or until commencement of the next alternative therapy, which ever is earlier.
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Health Related Quality of Life (QoL) - Quality of life (QoL) will be measured by using the EQ-5D questionnaire over the study period. QoL for patients will be measured until their first disease progression up to 2 years (estimated) which ever is earlier.
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Liver resection rate - Patients will be assessed for suitability for liver resection every 12 weekly until their study conclusion up to 2 years which ever is earlier.
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Liver Transplantation Rate - Patients will be assessed for suitability for liver transplantation every 12 weekly until their study conclusion up to 2 years which ever is earlier.
Timepoint [7] 0 0
Up to 2 years
Secondary outcome [8] 0 0
Time to Disease Progression - Time to Disease Progression (TTP) is defined as a measure of time after a disease is diagnosed (or treated) until the disease starts to get worse. Disease Progression will be measured by RECIST guideline version 1.1. TTP will be measured every 12 weekly up to 2 years (estimated).
Timepoint [8] 0 0
Up to 2 years
Secondary outcome [9] 0 0
Disease control rate
Timepoint [9] 0 0
2 years

Eligibility
Key inclusion criteria
- Disease must be locally advanced as defined by BCLC (B) intermediate stage or BCLC (C)
advanced stage without extra-hepatic disease (only with branch portal vein
thrombosis).

- Willing, able and mentally competent to provide written informed consent prior to any
testing undertaken for this study protocol, including screening tests and evaluations
that are not considered to be part of the subject's routine care.

- Aged 18 years/older (either gender).

- Unequivocal diagnosis of HCC.

- HCC not amenable to surgical resection or immediate liver transplantation, or cannot
be optimally treated with local ablative techniques such as RFA, consistent with the
practice of the clinical trial centre.

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded) as = 10 mm with spiral CT
scan or MRI.

- ECOG performance status 0-1.

- Child-Pugh A-B (up to 7 points)

- Adequate haematological, renal and hepatic function as follows:

- Leukocytes = 2,500/µL

- Platelets = 80,000/µL

- Haemoglobin > 9.5g/dL

- Total bilirubin < 2.0mg/dL

- INR = 2.0

- ALP = 5 x institutional ULN

- AST and ALT = 5 x institutional ULN

- Albumin = 2.5g/dL

- Creatinine = 2.0mg/dL

- Life expectancy of at least 3 months without any active treatment.

- Suitable for protocol treatment as determined by clinical assessment undertaken by the
Investigator.

- Female patients must be either postmenopausal or, if premenopausal, must have a
negative pregnancy test and agree to use 2 forms of contraception if sexually active
during their study participation.

- 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have had more than 2 administrations of hepatic artery directed therapy.

- Subjects who have had hepatic artery directed therapy done < 4 weeks prior to study
entry.

- Have had systemic chemotherapy for HCC except for prior adjuvant or neoadjuvant
therapy given more than 6 months from enrolment.

- have had prior treatment with Sorafenib or VEGF inhibitors.

- Prior hepatic radiation therapy for HCC or other malignancy.

- Currently receiving any other investigational agents for the treatment of their
cancer.

- Has intractable clinical ascites (in spite of optimal diuretic treatment) or any other
clinical signs of liver failure, on physical examination.

- Complete main portal vein thrombosis.

- Any metastatic disease (local-regional lymph nodes measuring less than 2 cm in
greatest diameter or lung nodules measuring less than 1 cm are not contraindications
as per Investigator discretion).

- Any other concurrent malignancy, except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
been disease-free for at least 5 years.

- Presence of clinical signs of CNS metastases due to their poor prognosis and because
progressive neurologic dysfunction would confound the evaluation of neurologic and
other adverse events.

- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection (except viral hepatitis), symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements.

- Any of the following contraindications to angiography and selective visceral
catheterization:

- Bleeding diathesis, not correctable by the standard forms of therapy.

- Severe peripheral vascular disease that would preclude arterial catheterization.

- Portal hypertension with hepato-fugal flow as documented on baseline spiral CT scan.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to SIR-Spheres or Sorafenib.

- Inability or unwillingness to understand or sign a written informed consent document.

- Female subjects who are pregnant or currently breastfeeding.

- Female subjects, unless postmenopausal or surgically sterile, unwillingness to
practice effective contraception, as per Investigator discretion during the study. The
rhythm method is not to be used as the sole method of contraception.

- Male subjects, unwillingness to practice effective contraception (per Investigator
discretion) while taking part in this study, because the effect of the SIR-Spheres
treatment on sperm or upon the development of an unborn child are unknown.

- Current enrolment in any other investigational therapeutic drug or device study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Brunei Darussalam
State/province [1] 0 0
Brunei
Country [2] 0 0
China
State/province [2] 0 0
Hong Kong
Country [3] 0 0
Indonesia
State/province [3] 0 0
Bali
Country [4] 0 0
Indonesia
State/province [4] 0 0
Jakarta
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Seoul
Country [6] 0 0
Malaysia
State/province [6] 0 0
Sarawak
Country [7] 0 0
Malaysia
State/province [7] 0 0
Kuala Lumpur
Country [8] 0 0
Malaysia
State/province [8] 0 0
Penang
Country [9] 0 0
Mongolia
State/province [9] 0 0
Ulaanbaatar
Country [10] 0 0
Myanmar
State/province [10] 0 0
Yangon
Country [11] 0 0
New Zealand
State/province [11] 0 0
Auckland
Country [12] 0 0
Philippines
State/province [12] 0 0
Makati City
Country [13] 0 0
Philippines
State/province [13] 0 0
Manila
Country [14] 0 0
Philippines
State/province [14] 0 0
Davao
Country [15] 0 0
Singapore
State/province [15] 0 0
Singapore
Country [16] 0 0
Taiwan
State/province [16] 0 0
Taipei
Country [17] 0 0
Taiwan
State/province [17] 0 0
Taoyuan Hsien
Country [18] 0 0
Taiwan
State/province [18] 0 0
Kaohsiung
Country [19] 0 0
Taiwan
State/province [19] 0 0
Taichung
Country [20] 0 0
Thailand
State/province [20] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Other
Name
Singapore General Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Cancer Centre, Singapore
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
National Medical Research Council (NMRC), Singapore
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Singapore Clinical Research Institute
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Sirtex Medical
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to assess the efficacy of SIRT as compared with
Sorafenib in patients with locally advanced liver cancer in terms of overall survival (OS).

The Study null hypothesis is, there is no difference in overall survival between patients
receiving SIRT and those receiving Sorafenib therapy.
Trial website
https://clinicaltrials.gov/show/NCT01135056
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pierce KH Chow, MBBS, PhD
Address 0 0
National Cancer Centre, Singapore
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications