The purpose of this study is to determine the recommended dose of the combination therapy of sorafenib with hepatic arterial infusion of low dose cisplatin and fluorouracil on patients with advanced hepatocellular carcinoma (Phase I), and to evaluate the efficacy of this combination therapy in the recommended dose (Phase II).
In Phase I, there will be 9 to 18 patients enrolled. Cohorts of 3 to 6 patients will receive escalated dose of cisplatin and fluorouracil until the MTD is reached. There will be no intra-patient dose escalation. Sorafenib will be administered orally at a dose of 400mg bid for 28 days in the all patients. Cisplatin at the dose of 10-20mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 170-330mg/m2 will be administered continuously at day1-day5, and day8-day12 via the implanted catheter system. A cycle is defined as 28 days and 3 cycles of this combination therapy will be continued. At the end of each cycle, adverse effect will be evaluated and dose escalation will be determined. In Phase II, there will be 28 patients enrolled. Time to progression of this combination therapy at the recommended dose will be evaluated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Sorafenib will be administered orally at a dose of 400 mg bid for 28 days in the all patients. Cisplatin at the dose of 10-20 mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 170-330 mg/m2 will be administered continuously at day 1-day 5, and day8-day12 via the implanted catheter system. A cycle is defined as 28 days and 3 cycles of this combination therapy will be continued.
Kurume University Medical Center
Kurume, Fukuoka, Japan
Ogaki Municipal Hospital
Oogaki, Gifu, Japan
Kinki University School of Medicine
Ōsaka-sayama, Osaka, Japan
Dose limiting toxicity in phase I and Time to progression in Phase II
Time frame: Every 4 weeks
Phase I and II: Overall survival (OS)
Time frame: Every day
Phase I and II: Progression free survival (PFS)
Time frame: Every four weeks
Phase I: Time to progression (TTP)
Time frame: Every four weeks
Phase I and II: Response Rate (RR)
Time frame: Every four weeks
Phase I and II: Adverse effect (AE)
Time frame: Every four weeks
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