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Hepatocellular CarcinomaPhase 3SIRveNIBNCT01135056

Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC)

A Phase 3 study testing SIR-Spheres and Sorafenib tosylate in people with Hepatocellular Carcinoma, run by Singapore General Hospital at 29 sites in 12 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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). 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?
SIR-Spheres and Sorafenib tosylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
360 participants
Where
29 sitesin 12 countries
Study dates
Jul 2010to 31 Jul 2018
Phase
Phase 3
Are there results?
None posted in the registry

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

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

29 sites in 12 countries.

29 sites in 12 countries

South Korea5 sites

  • Severance Hospital, Yonsei University College of Medicine

    Seoul, 120-752

  • Korea University Anam Hospital

    Seoul, 136-705

  • Seoul St. Mary's Hospital

    Seoul, 137- 040

  • Asan Medical Center

    Seoul, 138-736

  • Seoul National University Bundang Hospital

    Seoul, 463-707

Other trials in South Korea

Taiwan5 sites

  • Kaohsiung Chang Gung Memorial Hospital

    Kaohsiung City, 833

  • China Medical University Hospital

    Taichung, 404

  • National Taiwan University Hospital

    Taipei City, Taipei, 100

  • Taipei Veterans General Hospital

    Taipei City, Taipei, 112

  • Chang Gung Memorial Hospital

    Taoyuan, Taoyuan Hsien

Other trials in Taiwan

Philippines4 sites

  • Davao Doctors Hospital

    Davao City

  • Makati Medical Center

    Manila, Makati City, 1229

  • The Medical City

    Pasig, Manila

  • St. Luke's Medical Center, Philippines

    Quezon City, Manila, 1102

Other trials in Philippines

Singapore4 sites

  • National University Hospital

    Singapore, 119075

  • Singapore General Hospital

    Singapore, 168608

  • National Cancer Center Singapore

    Singapore, 169610

  • Khoo Teck Puat Hospital

    Singapore, 768828

Other trials in Singapore

Malaysia3 sites

  • Penang Adventist Hospital

    George Town, Pulau Pinang, 10350

  • University Malaya Medical Center

    Kuala Lumpur

  • Sarawak General Hospital

    Kuching, Sarawak

Other trials in Malaysia

Indonesia2 sites

  • University of Udayana, Rumah Sakit Sanglah, Indonesia

    Denpasar, Bali, 80114

  • Cipto Mangunkusumo Hospital ,University of Indonesia

    Jakarta, 16424

Other trials in Indonesia

Brunei1 site

  • The Brunei Cancer Centre

    Kampung Jerudong, Brunei, 3122

Burma1 site

  • Yangon GI & Liver Centre

    Yangon, 11141

Other trials in Burma

China1 site

  • Queen Mary Hospital

    Hong Kong, Hong Kong

Other trials in China

Mongolia1 site

  • National Cancer Center of Mongolia

    Ulaanbaatar, 210648

Other trials in Mongolia

New Zealand1 site

  • Auckland City Hospital

    Grafton, Auckland, 1023

Other trials in New Zealand

Thailand1 site

  • Chulabhorn Hospital

    Bangkok, 10210

Other trials in Thailand

About this study

Official title: Phase III Multi-Centre Open-Label Randomized Controlled Trial of Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (SIRveNIB)

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.

Read the detailed description

Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide but unfortunately between 70 - 80% of all HCC are in the Asia-Pacific because of the prevalence of chronic viral hepatitis in the region. The increase in the prevalence of chronic hepatitis C in the Western world however predicts that HCC will similarly be an important cause of death there in the next 20 years.

Only 15-20% of HCC are today potentially curable by surgery at the time of diagnosis. Another 10-15% of patients may benefit from potentially curative locally ablative therapy such as radio-frequency ablation. Prognosis in the majority of patients has been dismal as conventional systemic therapies have been largely inefficacious. The first successfully trialed systemic targeted therapy, sorafenib (2007) prolonged survival by a modest average of 3 months in patients with good underlying liver function.

While the liver is radio-sensitive, external beam radiation causes significant radio-toxicity. To overcome this, selective internal radiation therapy (SIRT) was developed to deliver a radiation source directly to liver cancer via the arterial route. Sir-sphere is radioactive yttrium on a 90 micro-meter diameter resin carrier and is an established therapy in colorectal metastasis. Sir-sphere has been reported to cause significantly tumour regression in HCC.

This study will evaluate the efficacy of SIRT using SIR-Spheres yttrium-90 microspheres compared to sorafenib in the treatment of patients with locally advanced primary HCC.

Being tested
SIR-Spheres, Sorafenib tosylate
Keywords
Hepatocellular Carcinoma, Randomized, Open-label, Multi-Centre, Phase III, Sorafenib, SIR-Spheres
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SIR-SpheresDevice

    Also called Yttrium-90 Microspheres

    One time treatment. Dose administered based on tumour volume. Each vial is 3.0GBq.

  • Sorafenib tosylateDrug

    Also called Nexavar

    Oral Tablet, 400mg B.i.d, until progression or unacceptable toxicity develops

Study groups in NCT01135056
Study groupRoleWhat they receive
Sorafenib, Multikinase Inhibitor, TabletActive comparatorSorafenib 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.
Receives: Drug: Sorafenib tosylate
SIR-Spheres, Microspheres, DeviceActive comparatorSIR-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.
Receives: Device: SIR-Spheres

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 years

Secondary outcomes (9)

  1. 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.

    Measured: 2 years

  2. 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.

    Measured: 2 years

  3. 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

    Measured: 2 years

  4. 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.

    Measured: Up to 2 years

  5. 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.

    Measured: Up to 2 years

  6. 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.

    Measured: Up to 2 years

  7. 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.

    Measured: Up to 2 years

  8. 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).

    Measured: Up to 2 years

  9. Disease control rate

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2010 (estimated)
  2. Study startJul 2010
  3. Primary completion31 Jul 2018 (estimated)
  4. Study completion31 Jul 2018 (estimated)

Resources

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
360 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01135056
Sponsor's protocol ID
AHCC06
Acronym
SIRveNIB
Status last verified
Apr 2018
First submitted
24 May 2010
Last updated
24 Apr 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, Choo SP, Cheow PC, Chotipanich C, Lim K, Lesmana LA, Manuaba TW, Yoong BK, Raj A, Law CS, Cua IHY, Lobo RR, Teh CSC, Kim YH, Jong YW, Han HS, Bae SH, Yoon HK, Lee RC, Hung CF, Peng CY, Liang PC, Bartlett A, Kok KYY, Thng CH, Low AS, Goh ASW, Tay KH, Lo RHG, Goh BKP, Ng DCE, Lekurwale G, Liew WM, Gebski V, Mak KSW, Soo KC; Asia-Pacific Hepatocellular Carcinoma Trials Group. SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. J Clin Oncol. 2018 Jul 1;36(19):1913-1921. doi: 10.1200/JCO.2017.76.0892. Epub 2018 Mar 2.

    PubMed 29498924

  • Gandhi M, Choo SP, Thng CH, Tan SB, Low AS, Cheow PC, Goh AS, Tay KH, Lo RH, Goh BK, Wong JS, Ng DC, Soo KC, Liew WM, Chow PK; Asia-Pacific Hepatocellular Carcinoma Trials Group. Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial. BMC Cancer. 2016 Nov 7;16(1):856. doi: 10.1186/s12885-016-2868-y.

    PubMed 27821083

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SIR-Spheres and Sorafenib tosylate in people with Hepatocellular Carcinoma, run by Singapore General Hospital at 29 sites in 12 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 22 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 24 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in South Korea, Taiwan, Philippines, Singapore, Malaysia and 7 more countries. 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?

Results are not available in the source record.

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?

Overall Survival (time frame: 2 years). 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 NCT01135056, which also lists 2 linked publications.

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 24 Apr 2018.

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