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

NCT00712790 | Completed Phase 1

• 1 other identifier: NMRC - AHCC05
• Study Type: interventional
• Target: 35
• Locations: 4 countries
• Sites: 5

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.

Conditions

Hepatocellular Carcinoma

Keywords

First line treatment for Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Toxicity and safety

  2 years

• Tumour response rate (liver ± any site).

  2 years

Secondary Outcomes (6)

• Progression free survival at any site.

  2 years

• Progression free survival in the liver.

  2 years

• Survival

  2 years

• Hepatic and extra-hepatic recurrence rate.

  2 years

• Quality of life.

  2 years

Study Arms (1)

Sequential Radioembolization-Sorafenib

EXPERIMENTAL

Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (Y) resin microspheres given as a single procedure.

Drug: Sorafenib; Radiation: SIR-Spheres

Interventions

Sorafenib DRUG

Tablet, 400mg orally, twice daily

Also known as: BAY 43-9006

Sequential Radioembolization-Sorafenib

SIR-Spheres RADIATION

one time treatment and capped at 3.0 Gbq

Also known as: Yttrium-90 Microspheres

Sequential Radioembolization-Sorafenib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Singapore Clinical Research Institute: lead
• National Medical Research Council (NMRC), Singapore: collaborator
• Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma: collaborator
• Sirtex Medical: collaborator

Study Sites (5)

Yangon GI & Liver Centre

Yangon, Burma

Location

Selayang Hospital

Kuala Selangor, Malaysia

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Seoul National University Bundang Hospital

Seoul, South Korea

Location

Related Publications (1)

• Chow PK, Poon DY, Khin MW, Singh H, Han HS, Goh AS, Choo SP, Lai HK, Lo RH, Tay KH, Lim TG, Gandhi M, Tan SB, Soo KC; Asia-Pacific Hepatocellular Carcinoma Trials Group. Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma. PLoS One. 2014 Mar 10;9(3):e90909. doi: 10.1371/journal.pone.0090909. eCollection 2014.

  PMID: 24614178 DERIVED

Related Links

• AHCC Trial 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 Chow, Phd

  SGH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MBBS MMed, FAMS, FRCSE, PhD | Senior Consultant Surgeon

Study Record Dates

• First Submitted: July 7, 2008
• First Posted: July 10, 2008
• Study Start: June 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: April 1, 2014
• Last Updated: January 6, 2016

Record last verified: 2016-01

Locations

MY (1); SG (2); KR (1); BU (1)