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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00712790
Recruitment Status : Completed
First Posted : July 10, 2008
Last Update Posted : January 6, 2016
National Medical Research Council (NMRC), Singapore
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Sirtex Medical
Information provided by (Responsible Party):
Pierce K.H.Chow, Singapore General Hospital

Brief Summary:

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 or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Sorafenib Radiation: SIR-Spheres Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : June 2008
Actual Primary Completion Date : June 2009
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Sequential Radioembolization-Sorafenib
Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (Y) resin microspheres given as a single procedure.
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

Primary Outcome Measures :
  1. Toxicity and safety [ Time Frame: 2 years ]
  2. Tumour response rate (liver ± any site). [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Progression free survival at any site. [ Time Frame: 2 years ]
  2. Progression free survival in the liver. [ Time Frame: 2 years ]
  3. Survival [ Time Frame: 2 years ]
  4. Hepatic and extra-hepatic recurrence rate. [ Time Frame: 2 years ]
  5. Quality of life. [ Time Frame: 2 years ]
  6. Rate of downstaging to surgical resection or ablative therapy. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00712790

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

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Pierce K.H.Chow, MBBS MMed, FAMS, FRCSE, PhD | Senior Consultant Surgeon, Singapore General Hospital Identifier: NCT00712790     History of Changes
Other Study ID Numbers: NMRC - AHCC05
First Posted: July 10, 2008    Key Record Dates
Last Update Posted: January 6, 2016
Last Verified: January 2016
Keywords provided by Pierce K.H.Chow, Singapore General Hospital:
First line treatment for Hepatocellular Carcinoma
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action