A Phase Ib Study of Stereotactic Radiotherapy (SBRT) Plus Sorafenib in Patients With Unresectable Hepatocellular Carcinoma (HCC)
4.1.1Age ≥ 18 years. 4.1.2 Patients with HCC without cirrhosis or with CTP class A
(maximum score 6).
4.1.3 Patient must not be a surgical candidate at presentation. 4.1.4 Able to undergo
contrast enhanced MRI of the primary tumor using the liver MRI protocol.
4.1.5 Measurable disease per mRECIST criteria defined as lesions >/=1cm showing
intratumoral arterial enhancement in contrast-enhanced CT or MRI and being suitable for
4.1.6 Must not have evidence of metastatic disease. 4.1.7 Karnofsky performance status
>/=70% 4.1.8 Life expectancy ≥ 3 months as determined by the treating physician. 4.1.9 If
single tumor, maximum tumor diameter must be = 6 cm. 4.1.10 No more than three discrete
liver lesions, with the overall sum of diameters being = 6 cm.
4.1.11 None of the lesions to be treated can be in closer than 0.5 cm to the wall of the
stomach, duodenum, or hepatic flexure of the colon.
4.1.12 Radiotherapy treatment planning confirms one of the following:
- One third of the uninvolved liver should receive =10 Gy
- At least 500 cc of uninvolved liver should receive =7 Gy 4.1.13 Radiotherapy
treatment planning confirms all of the following parameters for other normal tissues
- Maximal cord dose: 600 cGy per fraction x3 for a total of 18 Gy.
- Right kidney: <2/3 of the kidney volume receives > 15 Gy total dose and
- Left Kidney: < 1/3 receives > 15 Gy total dose. 4.1.14 Must fit in the stereotactic
body immobilization device as per institutional or manufacturer guidelines.
4.1.15 Patients must have adequate liver function within 2 weeks of study registration.
Adequate liver function is defined as all of the following:
- total bilirubin < 3mg/dL
- albumin >/= 2.5 g/dL
- INR = 1.5 and
- no greater than mild elevation of transaminases (AST, ALT < 5 x ULN) 4.1.16 Patients
must have adequate renal function within 2 weeks of study registration. Adequate
renal function is defined as one of the following:
- creatinine < 1.8 mg/dl or
- creatinine clearance (CrCL) >/= 50 ml/min. 4.1.17 Adequate bone marrow reserve within
2 weeks of study registration, defined as all of the following:
- ANC count >/=1500 mm3
- Platelets >/=50,000/mm3
- Hemoglobin > 9g/dL 4.1.18 No history of atherosclerotic coronary artery disease that
required bypass surgery, unless 1) bypass surgery occurred more than 12 months prior
to enrollment, and 2) disease is stable (in consultation with a cardiologist).
4.1.19 Women must not be pregnant or breastfeeding. The effects of Sorafenib on the
developing human fetus are unknown. For this reason and because radiation therapy and
Sorafenib used in this trial are may be teratogenic, women of child-bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth control)
prior to study entry and for the duration of study participation. Should a woman become
pregnant or suspect she is pregnant while participating in this study, she should inform
her treating physician immediately.
4.1.20 No history of HIV positivity, as the effects of sorafenib combined with radiation
therapy on patients with HIV are unknown. Patients with known HIV risk factors (as
determined by the treating physician) will be not eligible for this study without HIV
4.1.21 Must be able to provide written informed consent and HIPAA authorization.
4.2.1 Medical history of systemic lupus erythematous, rheumatoid arthritis, systemic
sclerosis or scleroderma.
4.2.2 Prior radiation therapy to the abdomen 4.2.3 Prior treatment with Sorafenib or other
Ras or VEGF pathway inhibitor. 4.2.4 Minor surgical procedure (e.g fine needle aspiration
or needle biopsy) within 7 days of study registration.
4.2.5 Major surgical procedure, significant traumatic injury, or serious non-healing
wound, ulcer or bone fracture within 21 days of study registration; investigator has to
document adequate healing has occurred prior to study registration.
4.2.6 Any of the following within 6 months prior to study drug administration:
severe/unstable angina (angina symptoms at rest), new onset angina (began within the last
3 months) or myocardial infarction, congestive heart failure, cardiac ventricular
arrhythmias requiring anti-arrhythmic therapy.
4.2.7 History of thrombotic or embolic events such as cerebrovascular accident or
transient ischemic attack within the past 6 months.
4.2.8 History of aneurysm or arteriovenous malformation. 4.2.9 Active, clinically serious
infection >/= CTCAE grade 2. 4.2.10 Receipt of any investigational agent within 4 weeks of
4.2.11 Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or
diastolic pressure > 90 mmHg, despite optimal medical management 4.2.12 Pulmonary
hemorrhage/bleeding event ≥CTCAE Grade 2 within 4 weeks of study registration 4.2.13 Any
other hemorrhage/bleeding event including esophageal variceal bleeding >/= CTCAE Grade 3
within 4 weeks of study registration.
4.2.14 Evidence or history of bleeding diathesis or coagulopathy 4.2.15 Chronic, daily
treatment with nonsteroidal anti-inflammatory medications. (Daily aspirin use is
permitted) 4.2.16 Use of carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), rifabutin
(Mycobutin), rifampin/ rifampicin (Rifadin, Rimactane), or ritonavir (Norvir).
4.2.17 Known or suspected allergy to Sorafenib or any agent given in the course of this
4.2.18 Any condition that impairs patient's ability to swallow whole pills. 4.2.19 Any
malabsorption problem that would impair the patient's ability to absorb oral medication.
4.2.20 Other severe, acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study drug
administration, or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this