Trial Information

Intergroup Protocol for Treatment of Children With Hepatoblastoma

PRIMARY OBJECTIVES:

I. To estimate the response and efficacy of amifostine (amifostine trihydrate) in reducing
the toxicity associated with platinum agents.

II. To test whether there is any effect of amifostine on event-free survival by comparing
outcome of those treated with amifostine to those treated without on this study and with
historic controls.

SECONDARY OBJECTIVES:

I. To estimate the event-free survival of patients with stage I pure fetal histology treated
with surgery alone.

II. To estimate the efficacy of amifostine in reducing the toxicity associated with
cisplatinum in children with resected tumors receiving treatment 01 by randomizing to
receive or not receive amifostine.

III. To collect tumor tissue in all patients for cytogenetic and genetic analysis in order
to prospectively analyze biologic features and prognosis of patients with detailed treatment
history, and to provide a resource for future biologic studies in hepatoblastoma.

IV. To assess the prognostic significance with respect to event-free survival of
hepatoblastoma pathologic variants in patients with stage I tumors treated with surgery and
chemotherapy (cisplatin + 5FU + vincristine).

OUTLINE: This is a randomized study. Patients are stratified according to disease stage
(stage I pure fetal histology vs stage I other histology or stage II [stage II closed to
accrual as of 11-25-03] vs stage III or IV [stages III and IV closed to accrual as of
11-25-03]). Patients are randomized to one of four treatment arms. (Arms III and IV closed
to accrual as of 4-5-02) (Arm II closed to accrual as of 11-25-03)

All patients undergo surgical resection or attempted resection of tumor. Patients with pure
fetal histology achieving complete tumor resection receive no further treatment. All other
patients receive postoperative chemotherapy.

Arm I: Patients receive cisplatin IV over 4 hours on day 1, vincristine IV on days 3, 10,
and 17, and fluorouracil on day 3.

Arm II (closed to accrual as of 11-25-03): Patients receive treatment as in arm I with the
addition of amifostine IV over 15 minutes prior to cisplatin on day 1.

Arm III (closed to accrual as of 4-5-02): Patients receive carboplatin IV over 1 hour on day
1 and cisplatin IV over 4 hours on day 15.

Arm IV (closed to accrual as of 4-5-02): Patients receive treatment as in arm III with the
addition of amifostine IV over 15 minutes prior to carboplatin on day 1.

Treatment repeats every 3 weeks for 4 courses in arms I and II (arm II closed to accrual as
of 11-25-03) and every 4 weeks for 4 courses in arms III and IV (arms III and IV closed to
accrual as of 4-5-02) in the absence of disease progression or unacceptable toxicity.
Patients with stage III or IV disease (stages III and IV closed to accrual as of 11-25-03)
undergo second look surgery and receive 2 additional courses of chemotherapy if achieving
complete response after surgery.

Patients are followed monthly for 6 months, every 2 months for 2 years, every 3 months for 2
years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 356 patients will be accrued for this study within 5.5 years.