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

NCT01135056 | Unknown Phase 3 DMC

• 1 other identifier: AHCC06
• Study Type: interventional
• Target: 360
• Locations: 12 countries
• Sites: 29

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Randomized; Open-label; Multi-Centre; Phase III; Sorafenib; SIR-Spheres

Outcome Measures

Primary Outcomes (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.

  2 years

Secondary Outcomes (9)

• Progression free survival in the liver

  2 years

• Progression free survival overall

  2 years

• Tumour Response Rate

  2 years

• Toxicity and Safety

  Up to 2 years

• Health Related Quality of Life (QoL)

  Up to 2 years

Study Arms (2)

Sorafenib, Multikinase Inhibitor, Tablet

ACTIVE COMPARATOR

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.

Drug: Sorafenib tosylate

SIR-Spheres, Microspheres, Device

ACTIVE COMPARATOR

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.

Device: SIR-Spheres

Interventions

SIR-Spheres DEVICE

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

Also known as: Yttrium-90 Microspheres

SIR-Spheres, Microspheres, Device

Sorafenib tosylate DRUG

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

Also known as: Nexavar

Sorafenib, Multikinase Inhibitor, Tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Singapore General Hospital: lead
• National Cancer Centre, Singapore: collaborator
• National Medical Research Council (NMRC), Singapore: collaborator
• Singapore Clinical Research Institute: collaborator
• Sirtex Medical: collaborator

Study Sites (29)

The Brunei Cancer Centre

Kampong Jerudong, Brunei, 3122, Brunei

Location

Yangon GI & Liver Centre

Yangon, 11141, Burma

Location

Queen Mary Hospital

Hong Kong, Hong Kong, China

Location

University of Udayana, Rumah Sakit Sanglah, Indonesia

Denpasar, Bali, 80114, Indonesia

Location

Cipto Mangunkusumo Hospital ,University of Indonesia

Jakarta, 16424, Indonesia

Location

Penang Adventist Hospital

George Town, Pulau Pinang, 10350, Malaysia

Location

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Location

University Malaya Medical Center

Kuala Lumpur, Malaysia

Location

National Cancer Center of Mongolia

Ulaanbaatar, 210648, Mongolia

Location

Auckland City Hospital

Grafton, Auckland, 1023, New Zealand

Location

Makati Medical Center

Manila, Makati City, 1229, Philippines

Location

The Medical City

Pasig, Manila, Philippines

Location

St. Luke's Medical Center, Philippines

Quezon City, Manila, 1102, Philippines

Location

Davao Doctors Hospital

Davao City, Philippines

Location

National University Hospital

Singapore, 119075, Singapore

Location

Singapore General Hospital

Singapore, 168608, Singapore

Location

National Cancer Center Singapore

Singapore, 169610, Singapore

Location

Khoo Teck Puat Hospital

Singapore, 768828, Singapore

Location

Severance Hospital, Yonsei University College of Medicine

Seoul, 120-752, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

Seoul St. Mary's Hospital

Seoul, 137- 040, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Seoul National University Bundang Hospital

Seoul, 463-707, South Korea

Location

National Taiwan University Hospital

Taipei City, Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei City, Taipei, 112, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, Taoyuan Hsien, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Chulabhorn Hospital

Bangkok, 10210, Thailand

Location

Related Publications (2)

• 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.

  PMID: 29498924 DERIVED

• 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.

  PMID: 27821083 DERIVED

Related Links

• AHCC Trials Group

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Pierce KH Chow, MBBS, PhD

  National Cancer Centre, Singapore

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2010
• First Posted: June 2, 2010
• Study Start: July 1, 2010
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: April 24, 2018

Record last verified: 2018-04

Locations

NZ (1); TH (1); BR (1); BU (1); MY (3); ID (2); SG (4); TW (5); CN (1); MO (1); KR (5); PH (4)