A Study of ONCO-DOX in Locally Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is a prospective, multicenter study that will be conducted at up to 40 centers in the United States and Outside United States (OUS). Participants in the study will be randomly assigned to receive either ONCO-DOX or sorafenib treatment. This study will evaluate the study participants' outcomes (medical condition) after being treated with ONCO-DOX and compare it to those treated with sorafenib alone.

Detailed Description
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This is a prospective, two-arm, stratified then randomized (1:1), open label, controlled, multicenter Phase III trial to evaluate the safety and efficacy of ONCOZENE™ Microspheres loaded with doxorubicin (ONCO-DOX) in comparison with orally administered sorafenib in patients with unresectable, locally-advanced hepatocellular carcinoma (HCC). Patients will be stratified by ECOG Performance Status 0 versus 1, portal vein invasion (yes vs. no), and alpha feto protein <400 versus ≥400. They will then be randomized at each site within each stratum. The study will be conducted at up to 40 centers in the United States, Europe & Asia. Enrolled patients will be randomized with equal allocation by study site. Patients will be followed for two years after the onset of treatment. The study will assess prospectively the efficacy and safety of DEB-TACE (ONCO-DOX) in patients with unresectable, locally-advanced HCC. The primary objective of this study is to compare the overall survival between DEB-TACE (ONCO-DOX) and sorafenib treatment groups.

Official Title
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A Randomized Controlled Trial of Transcatheter Arterial Chemoembolization With Drug Eluting Beads (DEB-TACE) Versus Sorafenib in the Treatment of Unresectable, Locally Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma, Hepatoma, Liver Cell Carcinoma

Intervention / Treatment
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* Device: DEB-TACE
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent ≥18 years of age Diagnosis of HCC Locally advanced HCC Preserved liver function Eastern Cooperative Oncology Group 0 or 1 Exclusion Criteria: Presence of extra-hepatic spread of disease. Macrovascular invasion of lobar portal vein branches or main portal vein. Candidate for surgical resection, transplantation, or local ablation. Prior intra-arterial embolization, chemotherapy or systemic therapy for HCC. Any contraindication for TACE. Platelet count <50,000/mm3 or international normalized ratio >1.5. Previous treatment with anthracycline antibiotics (e.g. Doxorubicin) or sorafenib. Unstable coronary artery disease or recent myocardial infarct (i.e. within 1 year). Known ejection fraction < 50%. Current infections requiring antibiotic therapy. Suffering from a known bleeding disorder. Renal insufficiency (serum creatinine > 2 mg/dL). Aspartate aminotransferase and/or alanine transaminase >5 times upper limit of normal. Presence of advanced liver disease. Any contraindication for doxorubicin administration: Any co-morbid condition or social situation, which has a high likelihood of causing poor compliance with the study protocol or jeopardizes the patient's safety. Patient has another primary tumor, with the exception of conventional basal cell carcinoma, superficial bladder cancer, melanoma in situ, or treated prostate cancer currently without biochemical or radiographic evidence of active disease Participation in a clinical trial of an investigational device or drug within 4 weeks of study entry. Pregnant or breast-feeding patients.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DEB-TACE<br>ONCO-DOX (Doxorubicin loaded Microspheres) up to 150 mg per treatment; treatments can be repeated every 4-8 weeks until complete tumor response is achieved. | Device: DEB-TACE<br> <br> * Other names: ONCO-DOX;|
| Active Comparator: Sorafenib<br>200 mg Sorafenib twice daily; continue until unacceptable toxicity or unequivocal tumor progression | Drug: Sorafenib<br> <br> * Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival in HCC subjects with minimum follow-up of subjects to at least one year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression (TTP) determined by radiological assessment using mRECIST criteria | 2 years | 
| Time to Extrahepatic Spread | Time to Extrahepatic Spread for each subject | 2 years | 
| Proportion Progression Free | Proportion Progression-Free (PPF) at one year | 1 year | 
| Frequency of Treatment Emergent Adverse Events | The frequency of treatment emergent adverse events at 30 day, 3, 6, 9, 12, 18, and 24-months following the initial treatment. The proportions of patients in each arm experiencing treatment emergent adverse events will be presented descriptively with the number experiencing the event, the number evaluated, the percentage, and the exact two-sided 95% confidence interval. | 2 years |