Trial Information

A Phase II Trial of Oxaliplatin/Adriamycin/5 Fluorouracil in Continuous Infusion / Interferon α-2b (OXAFI) Combination as Neoadjuvant Therapy in Unresectable Non-Metastatic Hepatocellular Carcinoma

OBJECTIVES:

Primary

- Determine the response rate in patients with unresectable, nonmetastatic hepatocellular
carcinoma treated with neoadjuvant oxaliplatin, doxorubicin hydrochloride,
fluorouracil, and recombinant interferon alfa-2b.

Secondary

- Determine the overall survival of patients treated with this regimen.

- Determine the progression-free survival of patients treated with this regimen.

- Determine the rate of conversion to resectability of tumor in patients treated with
this regimen.

- Determine the toxicity profile of this regimen in these patients.

- Assess the quality of life of patients treated with this regimen.

- Correlate changes in serological markers of angiogenesis before and after treatment
with clinical outcome in these patients.

- Correlate and validate the use of functional imaging before and after treatment with
clinical outcome in these patients.

OUTLINE: Patients receive neoadjuvant OXAFI therapy comprising oxaliplatin IV and
doxorubicin hydrochloride IV on days 1, 8 and 15; fluorouracil IV continuously on days 1-28;
and recombinant interferon alfa-2b subcutaneously three times weekly in weeks 1-4. Treatment
repeats every 28 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Patients receive at least 2 courses of neoadjuvant therapy before
undergoing evaluation for response. Patients whose disease becomes resectable after
achieving a complete or partial response proceed to surgery. Patients whose disease remains
unresectable are reevaluated until their disease either becomes resectable, they complete
neoadjuvant therapy, or they meet discontinuation criteria.

At least 2 weeks after receiving neoadjuvant therapy, patients whose disease is resectable
undergo surgery for potentially complete resection of their tumors with curative intent.
Patients who achieve complete resection proceed to adjuvant therapy.

At least 4 weeks after surgery, patients may restart OXAFI as adjuvant therapy, provided
they have fully recovered from surgery and have received fewer than 6 courses of neoadjuvant
therapy. Adjuvant therapy repeats every 28 days for a total of 6 courses (including
neoadjuvant OXAFI) in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tissue collection at baseline and periodically during study for
evaluation of circulating and tissue biomarkers of angiogenesis. Serum from venous blood
samples is analyzed for concentration of VEGF by ELISA. Tumor tissue obtained before and
after treatment is examined for tumor VEGF expression, microvessel density, and cellular
proliferation by IHC.

Patients complete quality of life questionnaires at baseline, monthly during study
treatment, after course 6 of neoadjuvant chemotherapy, or upon discontinuation of study
treatment.

Patients are followed periodically for up to 5 years after curative resection of their
tumors.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.