Comparison Study of Sorafenib and 5-fluorouracil/Mitomycin for Metastatic Hepatocellular Carcinoma
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Phase 2 Trial Comparing Sorafenib and 5-fluorouracil/Mitomycin in Hepatocellular Carcinoma With Pulmonary Metastasis|
- Progression free survival (PFS) [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
- Time-to-progression (TTP) [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
- Objective tumor response rate [ Time Frame: Determined by CT scan at the end of every 2 cycles until progressive disease is documented or intolerable toxicity occurs ] [ Designated as safety issue: No ]
- Adverse event rates and the toxicities [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||November 2015|
|Estimated Study Completion Date:||July 2016|
|Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Experimental: The FM group
Patients in the FM group will be administered 5-FU plus mitomycin
15mg/kg/day continuous IV from day 1 to day 6 every 28 days.
Other Name: 5-fluorouracilDrug: Mitomycin
4mg/day IV push from day 1 to day 4 every 28 days
Active Comparator: The sorafenib group
Patients in the sorafenib group will be administered sorafenib
400 mg BID every 28 days
Other Name: Nexavar
Most HCC patients are diagnosed at advanced stages in Korea, but effective treatment strategies for advanced HCC have not been established. In particular, optimal treatment strategy for extrahepatic as well as intrahepatic recurrences following locoregional therapy (e.g., transarterial chemoembolization, radiofrequency ablation therapy, and percutaneous ethanol injection) is still a challenging issue. Extrahepatic metastasis has been encountered more frequently, being more problematic than before in the management of HCC due to the increased survival with effective locoregional treatments. The lung is the most common site of extrahepatic metastasis and the surgical resection of pulmonary metastatic lesions may result in improved survival in selected patients. Previous studies suggested that aggressive management including resection of the extrahepatic recurrence combined with locoregional therapy for intrahepatic HCC may offer long-term survival in selected patients with recurrent HCC following hepatectomy. Such an aggressive strategy has serious limitation in clinical practice in that extrahepatic recurrence usually present as multiple lesions. Systemic chemotherapy has been one of the most commonly used treatment modalities for patients with multiple extrahepatic metastasis. However, chemotherapy using either a single or combined cytotoxic agents provides only limited benefit for such patients. The aim of this study is to compare the efficacy of sorafenib to 5-fluorouracil/mitomycin in HCC patients with pulmonary metastasis whose intrahepatic tumors had been previously controlled with repeated locoregional therapies before the initiation of systemic chemotherapy.
- Experimental arm(the FM group): Patients receive 5-FU IV continuously over 10 hours on day 1~6 and mitomycin IV push on day 1~4. Treatment repeats every 28 days.
- Active Comparator arm(the sorafenib group): Patients will receive 2 tablets of sorafenib (200 mg/tablet) twice daily, orally on a continuous basis.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. During the treatment period, patients will have study visits on Day 1 of every cycle (every 4 weeks from start of study drug) and will receive CT/MRI assessment every 2 cycles (every 8 weeks). In the event of radiological progression confined to the liver, e.g. appearance of new nodules in the liver in areas previously not treated by locoregional therapies, patients will then also be treated with locoregional therapies such as TACE or local ablation as long as the they may still benefit from treatment. If patients are no longer amenable to locoregional therapies (in the case of untreatable progression), the study will be stopped and best supportive care be offered. This will be based on the investigator's clinical judgment of the subject's status.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01171482
|Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Korea, Republic of|
|Principal Investigator:||Jung-Hwan Yoon, M.D., Ph.D.||Seoul National University Hospital|