Comparison Study of Sorafenib and 5-fluorouracil/Mitomycin for Metastatic Hepatocellular Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Seoul National University Hospital
Sponsor:
Information provided by (Responsible Party):
Jung-Hwan Yoon, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01171482
First received: July 22, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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 has been controlled with locoregional therapies.


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: 5-FU
Drug: Mitomycin
Drug: sorafenib
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
Study Start Date: November 2010
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: The FM group
Patients in the FM group will be administered 5-FU plus mitomycin
Drug: 5-FU
15mg/kg/day continuous IV from day 1 to day 6 every 28 days.
Other Name: 5-fluorouracil
Drug: Mitomycin
4mg/day IV push from day 1 to day 4 every 28 days
Other Name: mitomycin
Active Comparator: The sorafenib group
Patients in the sorafenib group will be administered sorafenib
Drug: sorafenib
400 mg BID every 28 days
Other Name: Nexavar

Detailed Description:

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.

Outline:

  • 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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with clinical or histological diagnosis of HCC based on the guidelines of the AJCC
  • Patients with at least one, bi-dimensionally measurable, pulmonary metastasis without intrahepatic viable tumor (Viable tumor is defined as uptake of contrast agent in the arterial phase of dynamic CT or MRI.)
  • Patients who have received previous local therapy treatments (RFA, PEI, cryoablation, surgery, resection) to non-target lesions are eligible
  • Age : 20 years to 80 years
  • ECOG Performance Status of 0 to 1
  • Child-Pugh class A or B (Child-Pugh score 7)
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

    • Hb ≧ 9 g/dL
    • Absolute neutrophil count > 1000/mm3
    • Platelet count ≧ 60,000 /mm3
    • Adequate clotting function: INR < 1.5
    • Hepatic: AST and ALT < 5 X ULN
    • Renal: serum creatinine < 1.7mg/dL
    • Bilirubin ≦ 3 mg/dL

Exclusion Criteria:

  • Patients with diffuse infiltrative type of HCC that are poorly defined
  • Presence of hepatic encephalopathy and intractable ascites
  • Patients who are on a liver transplant list
  • The patient has received prior systemic chemotherapy
  • History of organ allograft
  • Active clinically serious infections (> grade 2 NCI-CTC version 3.0), including spontaneous bacterial peritonitis
  • History of cardiac disease: congestive heart failure > NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed), cardiac arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension and diabetes mellitus
  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
  • HIV infection or AIDS-related illness or serious acute or chronic illness (based on medical history)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01171482

Contacts
Contact: Jung-Hwan Yoon +82-2-2072-2731 yoonjh@snu.ac.kr

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Jung-Hwan Yoon, M.D., Ph.D. Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Jung-Hwan Yoon, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01171482     History of Changes
Other Study ID Numbers: 07-2010-010
Study First Received: July 22, 2010
Last Updated: December 2, 2013
Health Authority: Korea: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Mitomycins
Mitomycin
Sorafenib
Fluorouracil
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014