Hepatocellular Carcinoma, Hepatoma, Liver Cell Carcinoma
Conditions
Brief summary
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
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.
Interventions
DEVICEDEB-TACE
DRUGSorafenib
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 1 year | Overall survival in HCC subjects with minimum follow-up of subjects to at least one year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DEB-TACE ONCO-DOX (Doxorubicin loaded Microspheres) up to 150 mg per treatment; treatments could be repeated every 4-8 weeks until complete tumor response was achieved | 0 |
| Sorafenib 200 mg of Sorafenib twice daily; continue until unacceptable toxicity or unequivocal tumor progression | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Sorafenib |
|---|---|---|
| Age | 63 years | 63 years |
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment United States | 2 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 1 / 2 |
| serious Total, serious adverse events | 0 / 0 | 1 / 2 |
Outcome results
Primary
Overall Survival
Overall survival in HCC subjects with minimum follow-up of subjects to at least one year
Time frame: 1 year
Population: The planned analyses were not performed due to early termination.
Secondary
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.
Time frame: 2 years
Population: Study was terminated early. Adverse events were captured through the end of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib | Frequency of Treatment Emergent Adverse Events | 2 participants |
Secondary
Proportion Progression Free
Proportion Progression-Free (PPF) at one year
Time frame: 1 year
Population: The planned analyses were not performed due to early termination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DEB-TACE | Proportion Progression Free | 0 Participants |
| Sorafenib | Proportion Progression Free | 2 Participants |
Secondary
Time to Extrahepatic Spread
Time to Extrahepatic Spread for each subject
Time frame: 2 years
Population: The planned analyses were not performed due to early termination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DEB-TACE | Time to Extrahepatic Spread | 0 Participants |
| Sorafenib | Time to Extrahepatic Spread | 2 Participants |
Secondary
Time to Progression
Time to progression (TTP) determined by radiological assessment using mRECIST criteria
Time frame: 2 years
Population: The planned analyses were not performed due to early termination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DEB-TACE | Time to Progression | 0 Participants |
| Sorafenib | Time to Progression | 2 Participants |
Other Pre-specified
FACT-Hep Quality of Life
FACT-Hep quality of life instrument validated in patients with Hepatic cancer.
Time frame: 2 years
Other Pre-specified
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.
Time frame: 2 years