Working… Menu

Sorafenib Tosylate and Chemoembolization With Doxorubicin Hydrochloride and Mitomycin in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01011010
Recruitment Status : Completed
First Posted : November 11, 2009
Last Update Posted : January 5, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride and mitomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. Giving sorafenib tosylate together with chemoembolization may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of sorafenib tosylate when given together with chemoembolization with doxorubicin hydrochloride and mitomycin in treating patients with liver cancer that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Liver Cancer Drug: doxorubicin hydrochloride Drug: mitomycin C Drug: sorafenib tosylate Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:



  • To determine the safety of sorafenib tosylate when given in combination with transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride and mitomycin C in patients with unresectable hepatocellular carcinoma.


  • To estimate the time to progression (TTP) in patients treated with this regimen.
  • To estimate the overall survival (OS) of patients treated with this regimen.
  • To explore correlative relationships between measures of serum VEGF in the peri-procedure TACE period and changes with TACE and sorafenib tosylate as well as patient outcomes (TTP and OS).

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice daily on days 1-14. Patients then undergo transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride and mitomycin C on days 17-19*. Patients then receive oral sorafenib tosylate twice daily beginning after recovery from TACE and continuing in the absence of disease progression or unacceptable toxicity.

NOTE: *A second course of TACE may be administered within 8 weeks after the first TACE procedure.

Blood samples may be collected periodically for biomarker and pharmacokinetic analysis.

After completion of study treatment, patients are followed up at 3-4 weeks and then every 3 months for up to 3 years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Clinical Trial of Sorafenib in Combination With Transarterial Chemoembolization (TACE) in Patients With Unresectable Hepatocellular Carcinoma (HCC)
Actual Study Start Date : July 22, 2009
Actual Primary Completion Date : December 2012
Actual Study Completion Date : September 29, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
Drug Information available for: Sorafenib

Arm Intervention/treatment
Single Arm
Single Arm Trial
Drug: doxorubicin hydrochloride
TACE (day 18-20): Doxorubicin 50mg and mitomycin C 10mg mixed with lipoidal and injected in proportion to liver volume being treated, followed by embospheres. Administered until there is a "pruned tree" appearance on angiography. If a second TACE is to be performed it should be performed within 8 weeks of the first procedure.

Drug: mitomycin C
TACE (day 18-20): Doxorubicin 50mg and mitomycin C 10mg mixed with lipoidal and injected in proportion to liver volume being treated, followed by embospheres. Administered until there is a "pruned tree" appearance on angiography. If a second TACE is to be performed it should be performed within 8 weeks of the first procedure.

Drug: sorafenib tosylate
Sorafenib 400mg BID continuously post TACE beginning when LFTs return to entry criterion. Discontinue at time of disease progression (progression in a lobe that has already been embolized, new lesions in an untreated lobe, or evidence of extrahepatic progression).

Other: laboratory biomarker analysis
Serum VEGF levels are required: pre TACE (day of procedure, time B), 24 hours post TACE (+/- 6 hours, time C), day 7 post first TACE (± 1 day, time D), day 28 post reinitiation of sorafenib (± 3 days, time E). These levels will not be repeated for patients receiving a second TACE procedure.

Other: pharmacological study
Treatment with sorafenib will continue on a daily basis until disease progression (see definition protocol Section 7) or unacceptable toxicity is encountered. At the end of treatment, no further therapies are currently recommended.

Primary Outcome Measures :
  1. Safety and toxicity as assessed by NCI CTCAE v3.0 criteria [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 5 years ]
  2. Correlative studies [ Time Frame: 3 years ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of hepatocellular carcinoma (HCC), as defined by 1 of the following:

    • Tissue histology

      • Recurrence of previously resected HCC does not require tissue confirmation if there is clear radiographic recurrence, in the judgment of the investigator
    • AFP > 400 ng/mL with compatible mass on MRI
  • Locally advanced disease
  • Not eligible for surgical resection or immediate liver transplantation OR have refused such procedures
  • All disease must be amenable to embolization in one or two procedures
  • Measurable disease, according to modified HCC RECIST criteria

    • Must have radiographically documented measurable disease with at least one site of disease that is unidimensionally measurable as ≥ 10 mm on MRI
    • Lesions previously treated by radiofrequency ablation should not represent the only site of measurable disease
  • Childs-Pugh score ≤ 7
  • No complete thrombosis of the main portal vein

    • If unilateral portal vein thrombosis is present, must demonstrate radiographic evidence of adequate flow to the lobe to be embolized
  • No evidence of extrahepatic/metastatic disease, such as lymph node metastases, lung or bone metastases, or peritoneal carcinomatosis

    • Evidence of cirrhosis is acceptable as long as the lab parameters are met
  • No known brain metastases


  • ECOG performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Hemoglobin ≥ 9.0 g/dL
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³
  • Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
  • Total bilirubin ≤ 3 mg/dL
  • ALT and AST ≤ 5 times ULN
  • INR < 1.5
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
  • No other cancer within the past 3 years except for cervical carcinoma in situ, previously treated basal cell carcinoma, or superficial bladder tumors (Ta, Tis, or T1)
  • No NYHA class III or IV congestive heart failure
  • No unstable angina (anginal symptoms at rest) or new-onset angina within the past 3 months
  • No myocardial infarction within the past 6 months
  • No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • No uncontrolled hypertension (i.e., systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management)
  • No venous thrombotic or arterial embolic events (e.g., cerebrovascular accident, including transient ischemic attacks or venous thromboembolism) within the past 6 months
  • No pulmonary hemorrhage/bleeding event > CTCAE grade 2 within the past 12 weeks
  • No other hemorrhage/bleeding event > CTCAE grade 3 within the past 12 weeks
  • No variceal bleeding within past 12 weeks
  • No known grade 2 or 3 esophageal varices (endoscopic evaluation is not required for study entry)
  • No evidence or history of bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 12 weeks
  • No serious non-healing wound, ulcer, or bone fracture
  • No significant proteinuria (i.e., proteinuria > 1+ on urine dipstick)
  • No HIV positivity (by patient report)
  • No active hepatitis B or C, unless patient has been on stable medications for ≥ 2 months
  • No active clinically serious infections (> grade 2)
  • No active gastrointestinal malabsorption problem
  • No condition that would impair the patient's ability to swallow whole pills
  • No active drug or alcohol abuse
  • No known severe hypersensitivity or suspected allergy to sorafenib tosylate, any of its excipients, or other drugs used in this study
  • No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule


  • No prior systemic therapy, embolic therapy, or radiotherapy for HCC (e.g., chemotherapy, transarterial chemoembolization, transarterial embolization, or 90Y microspheres)
  • At least 4 weeks since prior liver resection or ablative therapy and recovered
  • No prior Raf/MEK/ERK-targeted therapy or VEGF-targeted therapy
  • More than 4 weeks since prior participation in any investigational drug study
  • More than 12 weeks since prior major surgery or open biopsy

    • Prior core liver biopsy allowed
  • No concurrent antiretroviral therapy for HIV
  • No concurrent chronic anticoagulation (other than 1 mg of warfarin daily for port patency)
  • No concurrent St. John wort or rifampin
  • No other concurrent anticancer therapy, radiotherapy, or investigational therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01011010

Layout table for location information
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Hanna H. Sanoff, MD UNC Lineberger Comprehensive Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center Identifier: NCT01011010    
Other Study ID Numbers: LCCC 0902
P30CA016086 ( U.S. NIH Grant/Contract )
CDR0000648296 ( Other Identifier: PDQ number )
First Posted: November 11, 2009    Key Record Dates
Last Update Posted: January 5, 2018
Last Verified: January 2018
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
adult primary hepatocellular carcinoma
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Alkylating Agents
Nucleic Acid Synthesis Inhibitors