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A Single-Center Proof of Concept Pilot Study to Evaluate the Safety, Efficacy, and Tolerability of Sorafenib Combined With Therasphere in Subjects With Hepatocellular Carcinoma Awaiting Liver Transplantation.

Phase 1
18 Years
Open (Enrolling)
Hepatocellular Carcinoma

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Trial Information

A Single-Center Proof of Concept Pilot Study to Evaluate the Safety, Efficacy, and Tolerability of Sorafenib Combined With Therasphere in Subjects With Hepatocellular Carcinoma Awaiting Liver Transplantation.

Because Hepatocellular carcinoma (HCC) grows by forming new blood vessels liver transplant
(OLT) offers the best chance for long term survival. However, with the growing number of
patients who require OLT, prolonged wait list times often lead to drop out from the
transplant list due to tumor progression. Some patients are granted an "upgrade",within the
generally accepted guidelines for transplant eligibility, in order to expedite the access of
patients with early HCC to transplantation before tumor progression. The use of therapies
like radioembolization also known as Yttrium-90 ([Y-90] a procedure where very small beads
coated with radiation are injected directly into the tumor through an artery in your groin)
while awaiting OLT has become common at most transplant centers, including Northwestern, to
help patients reach transplant. Additionally, these treatments are being used to move
patients to a status eligible for transplant. We are studying whether a combination approach
with systemic therapy and therapy applied directly to the liver, will be more successful
than a single therapy . Angiogenesis (a process involving the growth of new blood vessels
from pre-existing vessels) plays an important role in the early stages of HCC. A decrease in
angiogenesis both locally within the treated tumor as well as in any existing tumor cells,
not yet detected, would hopefully decrease the incidence of post transplant recurrence of
HCC. All subjects enrolled in this study will be treated with the use of Therasphere, Y-90,
which is composed of nonbiodegradable glass microspheres coated with the radioactive
compound Y-90 which are injected into the hepatic artery. The concentrated radioactive
microspheres within the tumor lead to "inside-out" radiation. Half of the subjects will be
treated with sorafenib (NEXAVAR®) in conjunction with Y-90. The determination of which
subjects will receive sorafenib will be made randomly, like the flip of a coin. Sorafenib
works by slowing the growth of the tumor cell , attacking the tumor from the outside.
Researchers hope to determine whether the subjects treated with sorafenib have an overall
improved response to liver directed therapy with Y-90 Therasphere.

Inclusion Criteria:

- Adult > 18 years olf of either gender

- Diagnosis of HCC confirmed by biopsy, CT, or MRI

- Able to carry out activities of daily living, awake >50% of waking hours

- Meets eligibility for liver transplantation

- No prior treatment for HCC

- Ability to understand and sign the informed consent

- Child-bearing women and any men agree to use two forms of birth control (one of
which should be a barrier method) during the course of therapy and for 8 weeks

Exclusion Criteria:

- Less than or = 18 years old

- Ineligible for transplant due to comorbid disease

- Renal Failure requiring dialysis of any kind

- Severe Cardiac disease

- History of a stroke

- Evidence of metastatic disease- or tumors that have spread outside the liver

- Known human immunodeficiency virus (HIV) infection

- Uncontrolled blood pressure (systolic > 160) despite medication(s)

- Major surgery within 4 weeks prior to the screening visit

- Active clinically serious infection

- Serious non-healing wound, ulcer, or bone fracture.

- History of gastrointestinal bleeding (GIB) within 6 weeks prior to the screening

- Prior transplant of any kind

- Must be able to swallow oral pills, tablets or capsules of any size

- Use of St. John's Wort or rifampin (rifampicin).

- Currently being treated with Inteferon and/or Ribavirin therapy due to the
thrombocytopenias, lymphopenias and anemias observed with use of these two

- Known or suspected allergy to sorafenib or any agent given in the course of this

- Any malabsorption problem

- Pregnancy or lactation. Women of childbearing potential must have a negative
pregnancy test 7 days prior to beginning therapy.

- No potential living donor transplant (LDT-donor identified and worked up by the time
of randomization into this study. If a living donor is later identified- the subject
will be allowed to continue in the study. Sorafenib will be stopped at a minimum of
7 days prior to transplant surgery.

- Active alcohol use, drug use, or a psychiatric disease that would, in the opinion of
the PI or a subinvestigator (sub-I), prevent the subject from complying with the
study protocol and/or endanger the subject during their participation in the study

- Inability of the potential subject to read, understand and sign the informed consent

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To Evaluate sorafenib as an adjunct to Y-90 for control of HCC as a bridge/downstage to transplant

Outcome Description:

Subjects randomized to receive Sorafenib take the drug for 2 weeks before treatment with Y90. They have imaing (CT/MRI) 2 weeks after starting Sorafenib then are treated. Post-treatment patients have blood drawn and adverse event evaluation at 2 weeks, 4 weeks, 6 weeks, and then every 6 weeks up to 1 year or time of transplant. Repeat imaging is done at 4 weeks, and then every 3 months post-treatment. Subjects not receiving Sorafenib are terated with Y90 and then are evaluated post-treatment the same as the subjects that receive the drug.

Outcome Time Frame:

Up to one year

Safety Issue:


Principal Investigator

Laura Kulik, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation


United States: Northwestern University IRB

Study ID:




Start Date:

February 2009

Completion Date:

July 2014

Related Keywords:

  • Hepatocellular Carcinoma
  • Subjects with primary hepatocellular carcinoma, intended for liver transplantation.
  • Carcinoma
  • Carcinoma, Hepatocellular



Northwestern Memorial HospitalChicago, Illinois  60611