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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
United States: Food and Drug Administration
|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|