Study of SIR-Spheres Plus Sorafenib as 1st Line Treatment for Non-resectable Primary Hepatocellular Carcinoma (HCC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Singapore Clinical Research Institute.
Recruitment status was  Active, not recruiting
National Medical Research Council (NMRC), Singapore
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Sirtex Medical
Information provided by:
Singapore Clinical Research Institute Identifier:
First received: July 7, 2008
Last updated: October 13, 2010
Last verified: August 2009

This Phase I/II trial will evaluate the safety and activity of chemo-radiotherapy comprising a regimen of Sorafenib chemotherapy plus SIR-Spheres yttrium-90 microspheres (chemo-radiotherapy, also known as "chemo-SIRT"), for first-line treatment of patients with primary hepatocellular carcinoma (HCC) in whom surgical resection is not feasible.

This study is designed as a prelude to a planned future randomised comparative study that will compare the efficacy of Sorafenib plus SIR-Spheres versus Sorafenib alone, in this patient population.

Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Sorafenib
Radiation: SIR-Spheres
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of SIR-Spheres Plus Sorafenib as First Line Treatment in Patients With Non-Resectable Primary Hepatocellular Carcinoma

Resource links provided by NLM:

Further study details as provided by Singapore Clinical Research Institute:

Primary Outcome Measures:
  • Toxicity and safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Tumour response rate (liver ± any site). [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression free survival at any site. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Progression free survival in the liver. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Hepatic and extra-hepatic recurrence rate. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Quality of life. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Rate of downstaging to surgical resection or ablative therapy. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 35
Study Start Date: June 2008
Estimated Study Completion Date: June 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sorafenib
    Tablet, 400mg orally, twice daily
    Other Name: BAY 43-9006
    Radiation: SIR-Spheres
    one time treatment and capped at 3.0 Gbq
    Other Name: Yttrium-90 Microspheres

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Unresectable HCC with or without systemic metastases.
  • Willing, able and mentally competent to provide written informed consent prior to any testing under this study protocol, including screening tests and evaluations that are not considered to be part of the subject's routine care.
  • Aged 18 years or older of either gender and any race, religion or socioeconomic group.
  • Unequivocal diagnosis of primary HCC (as defined above)
  • HCC that is not amenable to surgical resection or immediate liver transplantation, or that is not optimally treatable with local ablative techniques such as radio-frequency ablation, 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.
  • ECOG performance status 0 - 1.
  • Adequate haematological, renal and hepatic function as follows:
  • Leukocytes ≥ 2,500/μL
  • Absolute Neutrophil Count ≥ 1,500/μL
  • Platelets ≥ 50,000/μL
  • Haemoglobin > 9.5 g/dL
  • Total bilirubin ≤ 2.0 mg/dL (SIR-Spheres should not be administered as a whole liver treatment if the total bilirubin is > 2X the institutional upper limit of normal).
  • INR ≤ 2.0
  • ALP ≤ 5 x institutional upper limit of normal
  • AST / ALT ≤ 5 x institutional upper limit of normal
  • Albumin ≥ 2.5 g/dL
  • Creatinine ≤ 2.0 mg/dL
  • The blood results must be less than 29 days old at the time of confirming patient eligibility to receive protocol treatment.
  • Life expectancy of at least 3 months without any active treatment. This is defined as a patient who has OKUDA I or II inoperable HCC.
  • 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 two 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.
  • Hepatic arterial anatomy suitable for implantation of SIR-Spheres, as assessed by hepatic angiogram.
  • Lung shunt fraction less than or equal to 20% as assessed by a Tc-99m macroaggregated albumin liver to lung breakthrough scan.

Exclusion Criteria:

  • Had previous external beam radiation therapy to the liver.
  • Any ascites or other clinical signs of liver failure, on physical examination.
  • Abnormal synthetic and excretory liver function tests (LFTs) as determined by serum albumin (must be < 2.5 g/dL) and total bilirubin (must be > 2.0 mg/dL), respectively.
  • Tumours amenable to surgical resection for cure at presentation.
  • Greater than 20% lung shunting of the hepatic artery blood flow determined by Tc-99 MAA scan.
  • Pre-assessment angiogram and Tc-99 MAA scan that demonstrates significant and uncorrectable activity in the stomach, pancreas or bowel.
  • Been treated with Capecitabine within the previous 8 weeks, or who will be treated with Capecitabine within 8 weeks of treatment with SIR-Spheres, due to the possible risk of potentiating or causing liver dysfunction.
  • Complete main portal vein thrombosis.
  • Subjects who have had hepatic artery directed therapy.
  • Subjects who have had prior chemotherapy or other medical agents used to treat hepatocellular carcinoma.
  • Prior external hepatic radiation therapy for HCC, or any other concomitant therapy for HCC or any investigational agent planned while on this protocol.
  • Subjects with inferior vena cava (IVC) tumour thrombus or invasion
  • Currently receiving any other investigational agents for the treatment of their cancer.
  • 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 five 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 intercurrent 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 hepatofugal flow as documented on baseline spiral CT scan.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres.
  • Inability or unwillingness to understand or sign a written informed consent document (non English-speaking patients may use an interpreter).
  • Female subjects who are pregnant or currently breastfeeding.
  • For female subjects, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception, as defined by the Investigator, during the study. The rhythm method is not to be used as the sole method of contraception.
  • For male subjects, unwillingness to practice effective contraception (as defined by the Investigator) 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 drug or device study.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00712790

Korea, Republic of
Seoul National University Bundang Hospital
Seoul, Korea, Republic of
Selayang Hospital
Selangor, Malaysia
Yangon GI & Liver Centre
Yangon, Myanmar
National Cancer Centre
Singapore, Singapore, 169610
Singapore General Hospital
Singapore, Singapore, 169608
Sponsors and Collaborators
Singapore Clinical Research Institute
National Medical Research Council (NMRC), Singapore
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Sirtex Medical
Study Chair: Pierce Chow, Phd SGH
  More Information

No publications provided by Singapore Clinical Research Institute

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: A/Prof Pierce Chow, Singapore General Hospital Identifier: NCT00712790     History of Changes
Other Study ID Numbers: NMRC - AHCC05
Study First Received: July 7, 2008
Last Updated: October 13, 2010
Health Authority: Singapore: Health Sciences Authority

Keywords provided by Singapore Clinical Research Institute:
First line treatment for Hepatocellular Carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses processed this record on December 01, 2015