A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma
I. To evaluate the tumor response rate in patients with hepatocellular carcinoma (HCC).
I. To determine other parameters of antitumor effect including time to tumor progression and
overall survival in HCC patients treated with bortezomib and doxorubicin.
II. To observe toxicity profile of bortezomib and doxorubicin in patients with
III. To evaluate proteasome 20S inhibition in tumor tissue (including proteins such as p21,
p27, p53, Bax and Bcl-2 which are affected by proteasome 26S) and compare to clinical
parameters using biopsy specimens obtained from patients with HCC treated with bortezomib.
(Withdrawn as of 03-2007) IV. To measure phosphorylation of IkB in tumor tissue and compare
to clinical parameters using biopsy specimens obtained from patients with HCC treated with
bortezomib. (Withdrawn as of 03-2007) V. To evaluate the effect of bortezomib on 26S
proteasome activity in peripheral white blood cells (WBC's) and patient serum. Direct
measurement of 26S proteasome activity as well as proteins affected by proteasome 26S and
NF-kB will be analyzed. (Withdrawn as of 03-2007)
OUTLINE: This is a multicenter study.
Patients receive doxorubicin IV over 5-15 minutes on days 1 and 8. Patients also receive
bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for
up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients
with no disease progression may continue to receive bortezomib alone in the absence of
disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 1 year.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 13 months.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rate as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 3 years
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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