A Study of ONCO-DOX in Locally Advanced Hepatocellular Carcinoma

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.

• DEB-TACE (Device), also known as ONCO-DOX
• Sorafenib (Drug), also known as Nexavar

Primary outcomes

• Overall Survival [1 year]: Overall survival in HCC subjects with minimum follow-up of subjects to at least one year

Secondary outcomes

• Time to Progression [2 years]: Time to progression (TTP) determined by radiological assessment using mRECIST criteria
• Time to Extrahepatic Spread [2 years]: Time to Extrahepatic Spread for each subject
• Proportion Progression Free [1 year]: Proportion Progression-Free (PPF) at one year
• Frequency of Treatment Emergent Adverse Events [2 years]: 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.

Other outcomes

• Proportion Achieved Tumor Response [2 years]: The proportion of patients in each group that achieve complete response (CR), partial response (PR), and stable disease (SD) will be presented and compared across treatment groups.
• FACT-Hep Quality of Life [2 years]: FACT-Hep quality of life instrument validated in patients with Hepatic cancer.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Written Informed Consent
2. ≥18 years of age
3. Diagnosis of HCC
4. Locally advanced HCC
5. Preserved liver function
6. Eastern Cooperative Oncology Group 0 or 1

Exclusion Criteria:

1. Presence of extra-hepatic spread of disease.
2. Macrovascular invasion of lobar portal vein branches or main portal vein.
3. Candidate for surgical resection, transplantation, or local ablation.
4. Prior intra-arterial embolization, chemotherapy or systemic therapy for HCC.
5. Any contraindication for TACE.
6. Platelet count <50,000/mm3 or international normalized ratio >1.5.
7. Previous treatment with anthracycline antibiotics (e.g. Doxorubicin) or sorafenib.
8. Unstable coronary artery disease or recent myocardial infarct (i.e. within 1 year).
9. Known ejection fraction < 50%.
10. Current infections requiring antibiotic therapy.
11. Suffering from a known bleeding disorder.
12. Renal insufficiency (serum creatinine > 2 mg/dL).
13. Aspartate aminotransferase and/or alanine transaminase >5 times upper limit of normal.
14. Presence of advanced liver disease.
15. Any contraindication for doxorubicin administration:
16. 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.
17. 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
18. Participation in a clinical trial of an investigational device or drug within 4 weeks of study entry.
19. Pregnant or breast-feeding patients.

Participant flow

Outcome results

• Overall Survival (Primary)
• Time to Progression (Secondary), Count of participants, Participants: DEB-TACE 0; Sorafenib 2
• Time to Extrahepatic Spread (Secondary), Count of participants, Participants: DEB-TACE 0; Sorafenib 2
• Proportion Progression Free (Secondary), Count of participants, Participants: DEB-TACE 0; Sorafenib 2
• Frequency of Treatment Emergent Adverse Events (Secondary), Number, participants: DEB-TACE ; Sorafenib 2
• Proportion Achieved Tumor Response (Other pre specified)
• FACT-Hep Quality of Life (Other pre specified)

Adverse events

Time frame: 2 months

Serious adverse events by term

Other adverse events by term

Limitations and caveats: The planned analyses were not performed due to early termination.

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form (PDF, 2015-05-15)

• Anastasia Becker, Study director, Boston Scientific Corporation