Clinical TrialsThe James Cancer Center Columbus, OH
open for enrollment
Sorafenib Tosylate with or without Stereotactic Body Radiation Therapy in Treating Patients with Liver Cancer
Randomized Phase III Study of Sorafenib versus Stereotactic Body Radiation Therapy followed by Sorafenib in Hepatocellular Carcinoma
This randomized phase III trial studies sorafenib tosylate and stereotactic radiosurgery (stereotactic body radiation therapy) to see how well they work compared to sorafenib tosylate alone in treating patients with liver cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stereotactic radiosurgery, also known as stereotactic body radiation therapy, uses focused, high-dose radiation to help shrink tumors. It is not yet known whether giving sorafenib tosylate together with stereotactic radiosurgery is more effective than sorafenib tosylate alone in treating liver cancer.
I. To determine if stereotactic body radiation therapy (SBRT) (stereotactic radiosurgery) improves overall survival in hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).
I. To determine the difference in time to progression (TTP) and progression-free survival (PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT followed by sorafenib.
III. To measure vascular thrombosis response post sorafenib versus SBRT followed by sorafenib.
IV. To measure differences in health related quality of life (QOL) and quality-adjusted survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
V. Collection of biospecimens for future correlative studies to investigate differences in potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo stereotactic radiosurgery every 24-72 hours for a total of 5 fractions over 5 to 15 days. Within 1-5 days post-stereotactic radiosurgery, patients receive sorafenib tosylate as in Arm I. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, and 12 months.
Are you eligible?
Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below =< 360 days prior to study entry
Pathologically (histologically or cytologically) proven diagnosis of HCC
At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava [IVC] and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis
For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI, in a patient with known HCC (diagnosed previously < 720 days)
Measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days of registration
Appropriate for protocol entry based upon the following minimum diagnostic workup:
History/physical examination including examination for encephalopathy, ascites, weight, height, and blood pressure within 14 days prior to study entry
Assessment by radiation oncologist and medical oncologist or hepatologist who specializes in treatment of HCC within 28 days prior to study entry
Pre-randomization scan (REQUIRED for all patients): CT scan chest/abdomen/pelvis with multiphasic liver CT or multiphasic liver magnetic resonance (MR) scan within 28 days prior to study entry; MRI of abdomen with contrast and pelvis is permitted
Zubrod performance status 0-2 within 28 days prior to study entry
Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
Platelets >= 70,000 cells/mm^3
Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
Total bilirubin < 2 mg/dL
Internationalized normal ratio (INR) < 1.7
Albumin >= 28 g/L
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 6 times upper limit of normal (ULN)
Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min
Barcelona Clinic Liver Cancer (BCLC) stage: intermediate (B) or advanced (C) within 14 days prior to study entry
Child-Pugh score A within 14 days prior to study entry
Women of childbearing potential and male participants must agree to practice adequate contraception while on study and for at least 6 months following the last dose of radiation therapy (RT) and for at least 28 days following the last dose of sorafenib (whichever is later)
Unsuitable for resection or transplant or radiofrequency ablation (RFA)
Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):
Technical contraindications: arteriovenous fistula, including surgical portosystemic shunt or spontaneous portosystemic shunt
Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion
Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease
Presence of extrahepatic disease
No response post TACE (or DEB) or progressive HCC despite TACE; prior TACE or DEB is allowed but must be > 28 days from study entry
Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be > 28 days from study entry
Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
Patients treated with prior surgery are eligible for this study if they otherwise meet eligibility criteria
Patient must be able to provide study-specific informed consent prior to study entry
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
Prior sorafenib use > 60 days; note that prior chemotherapy for HCC or a different cancer is allowable
Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields
Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
Severe, active co-morbidity, defined as follows:
Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months before registration
Transmural myocardial infarction within the last 6 months prior to study entry
Unstable ventricular arrhythmia within the last 6 months prior to study entry
Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry
Bleeding within 60 days prior to study entry due to any cause, requiring transfusion
Thrombolytic therapy within 28 days prior to study entry; subcutaneous heparin is permitted
Known bleeding or clotting disorder
Uncontrolled psychotic disorder
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
Any one hepatocellular carcinoma > 15 cm
Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC > 20 cm
More than 5 discrete intrahepatic parenchymal foci of HCC
Direct tumor extension into the stomach, duodenum, small bowel or large bowel
Measureable common or main branch biliary duct involvement with HCC
Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
Use of regular phenytoin, carbamazepine, hypericum perforatum (also known as St. John's wort) or rifampin
Use of combination anti-retroviral therapy for human immunodeficiency virus (HIV)
Prior liver transplant