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Phase I/II Study of Sorafenib In Combination With Low-dose FP Intraarterial Infusion Chemotherapy

Phase 1/Phase 2
20 Years
Not Enrolling
Hepatocellular Carcinoma

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Trial Information

Phase I/II Study of Sorafenib In Combination With Low-dose FP Intraarterial Infusion Chemotherapy

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.

Inclusion Criteria:

1. 20 Years and older.

2. Life expectancy of at least 12 weeks at the pre-treatment evaluation.

3. Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or
typical findings by dynamic CT or CT during hepatic arteriography/arterioportography.

4. Not suitable for resection or local ablation therapy or transcatheter arterial

5. One treatment of hepatic arterial infusion chemotherapy without implanted catheter
system is allowed.

6. ECOG Performance status of 0 or 1.

7. Cirrhotic status of Child-Pugh class A or B.

8. Adequate bone marrow, liver and renal function, as assessed by the following
laboratory requirements:

- Hemoglobin 8.5 g/dl

- Granulocytes 1500/μL

- Platelet count 50,000 /μL

- PT-INR 2.3 or PT 6 seconds above control

- Total serum bilirubin 2 mg/dl

- AST(SGOT) and ALT(SGPT) 5 × upper limit of normal

- Serum creatinine 1.5 × upper limit of normal

- Amylase 5 × upper limit of normal

9. Written Informed Consent must be obtained.

Exclusion Criteria:

1. 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

2. Renal failure

3. 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

4. Active clinically serious infections.

5. Active chicken pox.

6. Auditory disorder.

7. Known history of HIV infection.

8. Known metastatic or meningeal tumors.

9. Extrahepatic tumor spread.

10. History of seizure disorder.

11. Clinically significant gastrointestinal bleeding within 4 weeks prior to study entry.

12. Embolization or infarction such as transient ischemic disease, deep vein thrombosis,
pulmonary embolization).

13. Any history of treatment as follows:

- Treatment with the agent which induces CYP3A4

- Surgical procedure within 4 weeks prior to start of study drug

- History of organ allograft

14. Patients unable to swallow oral medications.

15. Gastrointestinal disease that may affect to the absorption of drug or

16. Medication that may affect to the absorption of drug or pharmacokinetics.

17. Any disease or disorder that may affect the evaluation of study drug.

18. Entry to the other clinical trial within 4 weeks prior to entry to this study.

19. Pregnant or breast-feeding patients.

20. Known allergy to the investigational agent or any agent given in association with
this trial.

21. Substance abuse, medical, psychological or social conditions that, in the judgment of
the investigator, is likely to interfere with the patient's participation in the
study or evaluation of the stuy results.

22. Any condition that is unstable or could jeopardize the safety of the patient and its
compliance in the study, in the investigator's judgment.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose limiting toxicity in phase I and Time to progression in Phase II

Outcome Time Frame:

Every 4 weeks

Safety Issue:


Principal Investigator

Masatoshi Kudo

Investigator Role:

Principal Investigator

Investigator Affiliation:

Japan Liver Oncology Group


Japan: Institutional Review Board

Study ID:




Start Date:

July 2009

Completion Date:

October 2010

Related Keywords:

  • Hepatocellular Carcinoma
  • sorafenib
  • intraarterial infusion chemotherapy
  • Low dose FP
  • cisplatin
  • fluorouracil
  • Carcinoma
  • Carcinoma, Hepatocellular