Trial Information

Intensified Pre-Operative Chemotherapy And Radical Surgery For High Risk Hepatoblastoma

OBJECTIVES:

Primary

- Determine the efficacy and short-term toxicity of intensified neoadjuvant chemotherapy
in children with high-risk hepatoblastoma undergoing surgical resection.

- Increase the rate of complete surgical resection in these patients by fully
implementing liver transplantation as a valid treatment option for tumor removal when
partial liver resection or other surgical options remain unfeasible even after
extensive preoperative chemotherapy.

- Determine, prospectively, the role of this regimen in rendering unresectable tumors
resectable in these patients.

- Determine the accuracy of initial imaging in predicting the surgical options (after
treatment with this regimen) for patients presenting with unresectable disease.

Secondary

- Determine the overall survival and event-free survival of patients treated with this
regimen (with an acceptable overall toxicity).

- Determine the toxicity of this regimen in these patients.

- Determine the response rate in patients treated with this regimen.

- Determine whether response to this regimen, defined by the modified RECIST criteria,
can be used for better monitoring of response in these patients.

- Determine whether a fall in alpha-fetoprotein during this neoadjuvant regimen can be
used as a prognostic factor in these patients.

- Determine, prospectively, radiological, surgical, and pathological characteristics of
the tumor that might identify possible novel factors that might influence treatment
choice and outcome in these patients.

OUTLINE: This is an open-label, multicenter study.

- Intensified neoadjuvant chemotherapy: Patients receive cisplatin IV over 24 hours on
days 1, 8, 15, 29, 36, 43, 57, and 64; and doxorubicin IV over 1 hour OR over 24 hours
on days 8, 9, 36, 37, 57, and 58. Patients determined to have resectable disease
proceed to surgery.

Patients determined to have unresectable disease after neoadjuvant chemotherapy receive
additional neoadjuvant chemotherapy comprising carboplatin IV over 1 hour on days 1 and 22
and doxorubicin IV over 1 hour OR over 24 hours on days 1, 2, 3, 22, 23, and 24.

Treatment continues in the absence of unacceptable toxicity.

- Surgery: Patients determined to have resectable disease undergo complete resection and
possibly liver transplantation.

- Adjuvant chemotherapy*: Patients who undergo complete surgical resection receive
carboplatin IV over 1 hour on day 1 and doxorubicin IV over 1 hour OR over 24 hours on
days 1 and 2. Treatment repeats every 3 weeks for a total of 3 courses.

NOTE: *Patients who received additional neoadjuvant chemotherapy for unresectable disease do
not receive adjuvant chemotherapy.

Patients are followed every 2-3 months for 2 years, every 3 months for 1 year, and then
every 6 months for 2 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 23-57 patients will be accrued for this study within 2 years.