Sorafenib Tosylate Before and After Hepatic Arterial Chemoembolization With Doxorubicin Hydrochloride and Mitomycin C in Treating Patients With Localized Liver Cancer That Cannot Be Removed by Surgery



Status:Recruiting
Conditions:Liver Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:1/1/2014
Start Date:July 2009

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Micro and Macro Ateriolar Blockade of Hepatocellular Carcinoma (HCC): Treatment With Sorafenib Before and After Hepatic Arterial Embolization (HAE) Therapy for Liver Cancer.

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 C, 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 blood flow to the tumor. Giving sorafenib tosylate before and after
chemoembolization may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving sorafenib
tosylate before and after hepatic arterial chemoembolization with doxorubicin hydrochloride
and mitomycin C works in treating patients with localized liver cancer that cannot be
removed by surgery.

OBJECTIVES:

Primary

- To evaluate the safety and tolerability of sorafenib tosylate therapy when administered
before and after doxorubicin hydrochloride-based hepatic arterial chemoembolization
(HACE) as assessed by NCI CTCAE v3.0 in patients with localized unresectable
hepatocellular carcinoma.

Secondary

- To determine if sorafenib tosylate decreases the number of HACE treatments required to
achieve radiologic tumor kill.

- To assess improvement in progression-free survival.

- To assess changes in monthly AFP levels in patients with AFP-producing tumors.

- To measure VEGF levels.

OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-14. Beginning ≥ 3
days later, patients undergo hepatic arterial chemoembolization (HACE)* with doxorubicin
hydrochloride and mitomycin C. Beginning ≥ 3 days after the completion of HACE and/or once
liver function returns to baseline, patients resume sorafenib tosylate twice daily for up to
6 months in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may undergo more than one HACE treatment.

Blood samples are collected periodically for further laboratory analysis.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed hepatocellular carcinoma (HCC)

- Single lesion > 6.5 cm; > 3 tumors, any tumor with a diameter > 4.5 cm; or a
cumulative tumor diameter > 8.0 cm

- Stage B (intermediate) disease according to the Barcelona Clinic Liver Cancer
(BCLC) classification system

- Unresectable, multinodular asymptomatic tumor

- No vascular invasion (including segmental portal invasion)

- No extrahepatic spread

- Stage C disease (according to the BCLC classification system) with portal vein
invasion that is limited to a sub-segmental branch of either the right or left
portal vein (i.e., sub-segmental portal vein invasion)

- Being considered for hepatic arterial embolization

- Must have ≥ 1 tumor lesion that can be accurately measured in ≥ 1 dimension according
to RECIST criteria

- The measurable lesion must not have been previously treated with local therapy
(e.g., surgery, radiotherapy, radiofrequency ablation, PEI, or cryoablation)

- Child Pugh class A-B7 liver function

- No diffuse HCC

- No unstable ascites

- No known brain metastasis or CNS disease

- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to
exclude brain metastasis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 12 weeks

- ANC ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 2 mg/dL

- ALT and AST ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with
liver involvement)

- Creatinine ≤ 1.5 mg/dL

- INR < 1.5 or PT/PTT normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment

- No cardiac disease, including any of the following:

- NYHA class III-IV congestive heart failure

- Unstable angina (anginal symptoms at rest) or new onset angina (within the past
3 months)

- Myocardial infarction within the past 6 months

- No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- No uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90
mm Hg, despite optimal medical management

- No known HIV infection

- No active clinically serious infection > CTCAE grade 2, except hepatitis B or C

- No thrombolic or embolic event (e.g., cerebrovascular accident, including transient
ischemic attacks) within the past 6 months

- No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks

- No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks

- No clinically significant gastrointestinal bleeding within the past 30 days

- No serious non-healing wound, ulcer, or bone fracture

- No evidence or history of bleeding diathesis or coagulopathy

- No significant traumatic injury within the past 4 weeks

- No known or suspected allergy to sorafenib tosylate or any agent given in the course
of this study

- No condition that would impair the ability to swallow whole pills

- No malabsorption problem

- No porto-systemic shunt

- No renal failure

- No severe atheromatosis

- No encephalopathy ≥ grade 1

- No contraindication for any of the following:

- Arterial procedure (e.g., impaired clotting tests [e.g., platelet count <
50,000/mm³ or prothrombin activity < 50%])

- Systemic chemotherapy administration (e.g., serum bilirubin > 5 mg/dL, leukocyte
count < 3,000/mm³)

- Sorafenib tosylate administration

- No substance abuse or medical, psychological, or social condition that would
interfere with study participation or evaluation of study results

- No other prior or concurrent cancer, except cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumor (Ta, Tis, or T1), or cancer that was
curatively treated > 3 years ago

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior surgery or open biopsy

- No prior systemic chemotherapy or targeted agents

- No concurrent St. John's wort or rifampin

- No concurrent therapy for hepatitis A, B, or C

- Concurrent anti-coagulation with warfarin or heparin allowed
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