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A Randomized Phase I/II, Multi-Center, Open-Label Trial of PR104 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Phase 1/Phase 2
18 Years
Not Enrolling
Hepatocellular Carcinoma

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Trial Information

A Randomized Phase I/II, Multi-Center, Open-Label Trial of PR104 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

A randomized phase I/II, multi-center, open-label, study with a single arm phase I portion
to determine the appropriate dose of PR104 combined with sorafenib, followed by a phase II
portion with randomization between sorafenib and sorafenib/PR104.

Following informed consent, subjects will undergo baseline evaluation with history, physical
exams, blood work and disease assessment. Selected subjects will undergo pharmacokinetic
assessment of sorafenib, PR104 and PR104 metabolites.

In the phase I portion of the study, subjects will be assigned to the current dose cohort
for PR104 in combination with standard dose sorafenib. PR104 will be administered on an
every 4 week schedule with the dose of PR104 escalated in a standard phase I fashion (3
subjects per cohort, dose escalation between cohorts) in order to determine the MTD of
PR104. Following determination of the MTD of PR104, new subjects will be entered into the
phase II portion of the study.

In the phase II portion of the study, subjects will be randomized between sorafenib, 400 mg,
PO, twice a day (the approved dose and schedule) versus sorafenib with PR104 at the dose
determined in the phase I portion of the study. PR104 will be administered every 4 weeks
(one cycle). Subjects will be evaluated each week during cycle 1 and every two weeks
thereafter. A disease assessment will be performed after every two cycles. Subjects with
progression will be removed from study. Subjects with a response or stable disease may
continue on study if this is considered beneficial by their physician.

Inclusion Criteria:

- Advanced-stage hepatocellular carcinoma considered non-operable that is suitable for
treatment with sorafenib. Subjects who have demonstrated progression following
initial surgical or locoregional therapy are eligible

- Confirmed hepatocellular carcinoma by pathological analysis (tissue aspirate or

- No previous systemic therapy for hepatocellular carcinoma

- ECOG Performance Status of 0 or 1

- Child-Pugh liver function class A

- Life expectancy of 12 weeks or more

- Adequate hematologic function (ANC ≥ 1.5 x 109/L; platelet count ≥100×109 per liter;
hemoglobin ≥8.5 g per deciliter maintained in the absence of red blood cell
transfusions; and prothrombin time international normalized ratio ≤1.7; or
prothrombin time ≤2 seconds above control)

- Adequate hepatic function (albumin ≥2.8 g per deciliter; total bilirubin ≤2 mg per
deciliter [51.3 μmol per liter]; and alanine aminotransferase and aspartate
aminotransferase ≤5 times the upper limit of the normal range)

- Adequate renal function (serum creatinine ≤1.5 times the upper limit of the normal
range or creatinine clearance ≥60 mL/min).

- At least one untreated target lesion that could be measured in one dimension,
according to the Response Evaluation Criteria in Solid Tumors (RECIST)

- Concomitant systemic antiviral therapy allowed

Exclusion Criteria:

- Previous molecularly targeted therapies or any other systemic treatment for
hepatocellular carcinoma

- Active concomitant malignancy likely to effect any of the primary or secondary
outcome measures in the current study

- Women who are pregnant, breast-feeding or planning to become pregnant during the

- Men or women of reproductive-potential who are unwilling to use an effective method
of contraception during the study and for 30 days following the last dose of study

- Evidence of a significant medical disorder or laboratory finding that, in the opinion
of the Investigator, compromises the subject's safety during study participation such
as: uncontrolled infection or infection requiring a concomitant parenteral
antibiotic; uncontrolled diabetes; congestive heart failure; myocardial infarction
within 6 months of study; chronic renal disease; or coagulopathy (excluding
prophylactic anticoagulation)

- Active CNS metastatic disease requiring intervention

- Less than four weeks since major surgery

- Known HIV positivity

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment


United States: Food and Drug Administration

Study ID:




Start Date:

March 2009

Completion Date:

May 2010

Related Keywords:

  • Hepatocellular Carcinoma
  • Carcinoma
  • Carcinoma, Hepatocellular



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Moores UCSD Cancer Center La Jolla, California  92093-0658
University of Arizona Tucson, Arizona  85724
Northwestern University Chicago, Illinois  60611
University of California, Irvine Orange, California  92868
Sharp Clinical Oncology Research San Diego, California  92123
Columbia University Medical Center New York, New York  10032
Indiana University Simon Cancer Center Indianapolis, Indiana  46202
Pacific Oncology/Hematology San Francisco, California  94115