A Study of ONCO-DOX in Locally Advanced Hepatocellular Carcinoma (SOLACE)

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

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma; Hepatoma; Liver Cell Carcinoma
• Intervention / Treatment: Device: DEB-TACE; Drug: Sorafenib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEB-TACE; 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; Other Names: ONCO-DOX
Active Comparator: Sorafenib; 200 mg Sorafenib twice daily; continue until unacceptable toxicity or unequivocal tumor progression	Drug: Sorafenib; Other Names: Nexavar

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion Achieved Tumor Response	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.	2 years
FACT-Hep Quality of Life	FACT-Hep quality of life instrument validated in patients with Hepatic cancer.	2 years

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Study Director: Anastasia Becker, Boston Scientific Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): June 5, 2017
• Study Completion (Actual): June 5, 2017

Study Registration Dates

• First Submitted: June 1, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 3, 2015

Study Record Updates

• Last Update Posted (Actual): February 12, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: SOLACE