SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The main purpose of this study is to determine the safety and toxicity of treatment with SIR-Spheres® in patients with unresectable primary liver cancer or hepatocellular carcinoma (HCC). Other purposes of this study include assessment of the effect of treatment on overall survival, the length of time it takes for the disease to worsen, if and how the treatment affects the patient's quality of life, and if and how the cancer responds to the treatment.

Detailed Description
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This study is a multi-institutional, non-randomized pilot study that aims to assess the safety and toxicity of hepatic arterial radioembolization using SIR-Spheres yttrium-90 microspheres (SIR-Spheres microspheres) in the treatment of patients with unresectable primary hepatocellular carcinoma (HCC). The study aims to recruit 40 patients over a period of 24 months.

Official Title
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A Pilot Study of Yttrium-90 Microspheres (SIR-Spheres®) Therapy for the Treatment of Unresectable Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular, Hepatoma

Intervention / Treatment
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* Device: SIR-Spheres microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: must have a confirmed diagnosis of HCC. at least 18 years of age. must have a confirmed diagnosis of HCC either by histological confirmation or, in a subject who exhibits a vascular liver mass in the presence of radiographically apparent cirrhosis, an alpha-fetoprotein (AFP) level greater than 500 International Units/milliliter (UI/ml). must present 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 due to its size, extent or presence of cirrhosis. must present measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as greater than or equal to 10 mm with spiral CT scan or greater than or equal to 20 mm using conventional techniques (CT, MRI). must present with a whole-liver tumor burden of greater than or equal to 15% and less than or equal to 70% must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. must have normal organ and marrow function Exclusion criteria: Includes both the listed contraindications to SIR-Spheres® and the exclusion criteria specific to the setting of this investigational study: hepatic artery directed therapy within the previous 6 months. chemotherapy within the previous 4 weeks have not recovered from adverse events due to agents administered previously Prior external hepatic radiation therapy for HCC, more than two prior systemic chemotherapy regimes for HCC or any other concomitant therapy for HCC Currently receiving any other investigational agents for the treatment of their cancer. Any extra-hepatic metastases other than metastatic disease found in the lung, bone and/or abdominal lymph nodes that are not otherwise life limiting. 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. Uncontrolled intercurrent illness 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 Severe peripheral vascular disease Portal hypertension with hepatofugal flow Female subjects who are pregnant or currently breastfeeding. Refusal or inability to use effective means of contraception in men or women of childbearing potential. Current enrollment in any other investigational drug or device study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SIR-Spheres microspheres<br>SIR-Spheres microspheres | Device: SIR-Spheres microspheres<br>* SIR-Spheres Yttrium-90 microspheres<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events Grade 3 or Higher | Using the National Cancer Institute Common Terminology Criteria (NCI-CTC) version 3.0 as recorded in the case report form. | From date of enrollment until the date of death from any cause assessed up 24 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks. | 
| Tumor Response Rate | Tumour response rates estimated by the proportion of patients with a best response of CR, PR or SD by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) with corresponding exact 90% confidence limits being reported. Per RECIST v1.0 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks. | 
| Change From Baseline in Health-related Quality of Life |  | 52 weeks | 
| Overall Survival | Overall Survival is defined as the time interval between the date of enrollment and the date of death from any cause. | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unresectable hepatocellular carcinoma, HCC, SIR-Spheres, Y-90 Microspheres, brachytherapy, Selective Internal Radiation Therapy (SIRT), liver cancer