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A Phase I Study of Sorafenib and Radiation Therapy in Patients With Hepatocellular Carcinoma

Phase 1
18 Years
Open (Enrolling)
Hepatocellular Carcinoma

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Trial Information

A Phase I Study of Sorafenib and Radiation Therapy in Patients With Hepatocellular Carcinoma

The study design will include 2 radiation strata of patients, with a constant radiation dose
for strata 1 requiring a low volume of liver to be irradiated, and a variable dose defined
based on the effective liver volume irradiated in the second strata, which will require more
liver volume to be irradiated, based on our prior experience. Both stratas one and two will
be accrued concurrently. Biologic response will be assessed using standard contrast CT
scans. Correlative studies of biological markers, perfusion CT, and microbubble contrast
enhanced ultrasound will also be performed.

Inclusion Criteria:

- Patients must have HCC either

- confirmed pathologically

- diagnosed by showing vascular enhancement of the lesion on at least two imaging

- diagnosed by showing vascular enhancement on a single technique if the AFP is
over 200, in the setting of cirrhosis or chronic hepatitis B without cirrhosis.
Biopsies are mandatory (unless an absolute contraindication exists).

- The tumour must be unresectable or medically inoperable

- At least 800 cc of non-tumor liver

- Patients must be > 4 weeks since any major surgery.

- Patients may have had previous systemic treatment (with at least a 2 week break from
systemic therapy to start of radiation therapy. Prior sorafenib or any other
targeted therapy with anti-VEGF activity is not permitted.

- Child-Pugh Liver score A

- Barcelona-Clinic Liver Cancer (BCLC) score A or B or C (BCLC C permitted if ECOG 0-1
and Child Pugh A, with portal invasion)

- Age 18 years or older.

- Life expectancy of equal to or greater than 3 months.

- ECOG performance status 0-1.

- Patients must have normal organ and marrow function.

- Ability to understand and the willingness to sign a written informed consent

- Negative pregnancy test for women of child bearing age

- If the patient has a history of varices and portal hypertension, elective treatment
(e.g. banding) of varices will be performed prior to start of radiation therapy.

- The effects of Sorafenib on the developing human fetus are unknown. For this reason
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation.

Exclusion Criteria:

- Serious medical conditions that might be aggravated by treatment, including but not
limited to: myocardial infarction within 6 months, congestive heart failure, unstable
angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled
psychotic disorders, serious infections, active peptic ulcer disease, active
hepatitis or cerebrovascular disease with previous stroke within the past 12 months.

- Patients may not be receiving any other investigational agents concurrently or within
2 weeks of initiation of treatment.

- Pregnant women

- Patients with immune deficiency

- Ascites (on imaging or clinical exam).

- Prior liver or upper abdomen radiation therapy.

- Resectable hepatocellular carcinoma.

- Thrombolytic therapy within 4 weeks, or any concurrent anti-coagulant therapy.

- Uncontrolled hypertension

- Patients with other active malignancies

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sorafenib.

- Patients with active hepatitis or encephalopathy related to liver failure.

- Patients with any bleeding or clotting disorder.

- Patients with unhealed wounds or ulcers.

- Prior sorafenib treatment is not permitted.

- Patient with nausea and vomiting refractory to medical therapies, significant prior
bowel resection, and inflammatory bowel disease.

- Patients with evidence of extrahepatic metastases

- Patients on Rifampin, St.John's Wort, Phenytonin, Carbamazepine, Phenobarbital, or
chronic use (more than 4 weeks) of dexamethasone.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the MTD of sorafenib and RT in patients with hepatocellular carcinoma using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT.

Outcome Time Frame:

1 year enrollment; 5 years follow-up

Safety Issue:


Principal Investigator

Laura Dawson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Princess Margaret Hospital


Canada: Ethics Review Committee

Study ID:

UHN REB 08-0761-C



Start Date:

January 2009

Completion Date:

January 2016

Related Keywords:

  • Hepatocellular Carcinoma
  • Sorafenib
  • Hepatocellular carcinoma
  • Carcinoma
  • Carcinoma, Hepatocellular