Phase I/II Study of Sorafenib In Combination With Low-dose FP Intraarterial Infusion Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- sorafenib, cisplatin, fluorouracil
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Kindai University
- Enrollment
- 37
- Locations
- 3
- Primary Endpoint
- Dose limiting toxicity in phase I and Time to progression in Phase II
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •20 Years and older.
- •Life expectancy of at least 12 weeks at the pre-treatment evaluation.
- •Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or typical findings by dynamic CT or CT during hepatic arteriography/arterioportography.
- •Not suitable for resection or local ablation therapy or transcatheter arterial chemoembolization.
- •One treatment of hepatic arterial infusion chemotherapy without implanted catheter system is allowed.
- •ECOG Performance status of 0 or
- •Cirrhotic status of Child-Pugh class A or B.
- •Adequate bone marrow, liver and renal function, as assessed by the following laboratory requirements:
- •Hemoglobin 8.5 g/dl
- •Granulocytes 1500/μL
Exclusion Criteria
- •Previous malignancy (except for cervical carcinoma in situ, adequate treated basal cell carcinoma, or superficial bladder tumors \[Ta, Tis and T1\], early gastric cancer, or other malignancies curatively treated \> 3 years prior to entry
- •Renal failure
- •Any heart disease as follows
- •Congestive heart failure defined as NYHA class III or IV
- •Active coronary artery disease or ischemic heart disease such as cardiac infarction within 6 months prior to screening
- •Serious cardiac arrhythmia
- •Serious hypertension
- •Active clinically serious infections.
- •Active chicken pox.
- •Auditory disorder.
Arms & Interventions
Sorafenib with Low-dose FP
Intervention: sorafenib, cisplatin, fluorouracil
Outcomes
Primary Outcomes
Dose limiting toxicity in phase I and Time to progression in Phase II
Time Frame: Every 4 weeks
Secondary Outcomes
- Phase I and II: Overall survival (OS)(Every day)
- Phase I and II: Progression free survival (PFS)(Every four weeks)
- Phase I: Time to progression (TTP)(Every four weeks)
- Phase I and II: Response Rate (RR)(Every four weeks)
- Phase I and II: Adverse effect (AE)(Every four weeks)