Sorafenib Tosylate and Chemoembolization With Doxorubicin Hydrochloride and Mitomycin in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride and mitomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. Giving sorafenib tosylate together with chemoembolization may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects of sorafenib tosylate when given together with chemoembolization with doxorubicin hydrochloride and mitomycin in treating patients with liver cancer that cannot be removed by surgery.
Drug: doxorubicin hydrochloride
Drug: mitomycin C
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase Ib Clinical Trial of Sorafenib in Combination With Transarterial Chemoembolization (TACE) in Patients With Unresectable Hepatocellular Carcinoma (HCC)|
- Safety and toxicity as assessed by NCI CTCAE v3.0 criteria [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Correlative studies [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2009|
|Estimated Study Completion Date:||November 2016|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Single Arm Trial
Drug: doxorubicin hydrochloride
TACE (day 18-20): Doxorubicin 50mg and mitomycin C 10mg mixed with lipoidal and injected in proportion to liver volume being treated, followed by embospheres. Administered until there is a "pruned tree" appearance on angiography. If a second TACE is to be performed it should be performed within 8 weeks of the first procedure.Drug: mitomycin C
TACE (day 18-20): Doxorubicin 50mg and mitomycin C 10mg mixed with lipoidal and injected in proportion to liver volume being treated, followed by embospheres. Administered until there is a "pruned tree" appearance on angiography. If a second TACE is to be performed it should be performed within 8 weeks of the first procedure.Drug: sorafenib tosylate
Sorafenib 400mg BID continuously post TACE beginning when LFTs return to entry criterion. Discontinue at time of disease progression (progression in a lobe that has already been embolized, new lesions in an untreated lobe, or evidence of extrahepatic progression).Other: laboratory biomarker analysis
Serum VEGF levels are required: pre TACE (day of procedure, time B), 24 hours post TACE (+/- 6 hours, time C), day 7 post first TACE (± 1 day, time D), day 28 post reinitiation of sorafenib (± 3 days, time E). These levels will not be repeated for patients receiving a second TACE procedure.Other: pharmacological study
Treatment with sorafenib will continue on a daily basis until disease progression (see definition protocol Section 7) or unacceptable toxicity is encountered. At the end of treatment, no further therapies are currently recommended.
- To determine the safety of sorafenib tosylate when given in combination with transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride and mitomycin C in patients with unresectable hepatocellular carcinoma.
- To estimate the time to progression (TTP) in patients treated with this regimen.
- To estimate the overall survival (OS) of patients treated with this regimen.
- To explore correlative relationships between measures of serum VEGF in the peri-procedure TACE period and changes with TACE and sorafenib tosylate as well as patient outcomes (TTP and OS).
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib tosylate twice daily on days 1-14. Patients then undergo transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride and mitomycin C on days 17-19*. Patients then receive oral sorafenib tosylate twice daily beginning after recovery from TACE and continuing in the absence of disease progression or unacceptable toxicity.
NOTE: *A second course of TACE may be administered within 8 weeks after the first TACE procedure.
Blood samples may be collected periodically for biomarker and pharmacokinetic analysis.
After completion of study treatment, patients are followed up at 3-4 weeks and then every 3 months for up to 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01011010
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|Principal Investigator:||Hanna H. Sanoff, MD||UNC Lineberger Comprehensive Cancer Center|