Trial Information

Hepatocellular Carcinoma Family of Tumours In Children / Adolescents and Young Adults

OBJECTIVES:

Primary

- Determine the event-free and overall survival of younger patients undergoing surgery
for newly diagnosed, noncirrhotic hepatocellular carcinoma (HCC) treated with
neoadjuvant cisplatin, doxorubicin hydrochloride, and thalidomide (PLADOTH) followed by
transarterial hepatic arterial chemoembolization comprising cisplatin and doxorubicin
hydrochloride and adjuvant cyclophosphamide and thalidomide.

- Determine the efficacy and tolerability of PLADOTH in patients with initially
unresectable noncirrhotic HCC treated with this regimen.

- Determine the rate of complete surgical resection by encouragement of liver
transplantation in the treatment strategy as a valid option for tumor removal when
partial liver resection or other surgical options remain unfeasible for patients
treated with this regimen.

- Determine the long-term remission and decreased relapse rates of patients treated with
this regimen based on the postoperative regimen.

Secondary

- Determine the response rate of patients treated with this regimen after treatment with
PLADOTH.

- Determine the short-term toxicity and feasibility of PLADOTH in patients treated with
this regimen.

- Determine the efficacy and toxicity of the postoperative regimen in terms of
maintenance and duration of complete remission (no more evidence of disease and normal
alpha-fetoprotein, if initially elevated) in patients treated with this regimen.

- Determine whether response to PLADOTH by the RECIST criteria can be used for better
monitoring of response of patients treated with this regimen.

- Determine whether the rate of fall of serum VEGF and bFGF levels during PLADOTH can be
used as prognostic factors for short-term and long-term outcome in patients treated
with this regimen.

- Determine the feasibility of chemoembolization in patients treated with this regimen
who do not respond to PLADOTH.

- Determine which subset of tumors may benefit from an angiostatic treatment approach
based on radiological, surgical, and pathological data collected from patients treated
with this regimen.

- Identify possible novel factors that might influence treatment choice and disease
outcome based on radiological, surgical, and pathological data collected from patients
treated with this regimen.

- Determine guidelines for diagnostic, therapeutic, and follow-up management that would
improve clinical care for patients treated with this regimen.

OUTLINE: This is a multicenter, nonrandomized, open-label study.

All patients undergo either tumor biopsy or resection. Patients with localized resectable
tumors undergo resection. They then proceed directly to the postoperative treatment.
Patients with initially unresectable tumors undergo biopsy then proceed to the pre-operative
regimen.

- Pre-operative chemotherapy and thalidomide (PLADOTH): Patients receive PLADOTH
comprising cisplatin IV continuously over 24 hours on day 1, doxorubicin hydrochloride
IV over 1 hour on days 1 and 2 (or IV continuously over 24 hours on days 1 and 3), and
oral thalidomide daily on days 1-21. Treatment repeats every 21 days for 4 courses in
the absence of disease progression or unacceptable toxicity. Patients whose tumors are
deemed resectable proceed to surgery. Patients with responding disease but whose tumors
remain unresectable proceed to chemoembolization or receive 2 additional courses of
PLADOTH.

- Transarterial hepatic artery chemoembolization (TACE): Patients undergo TACE comprising
cisplatin and doxorubicin hydrochloride administered through a catheter placed near the
tumor. TACE may be repeated every 3-4 weeks for as long as disease continues to respond
or until the tumor becomes resectable. Patients also receive oral thalidomide once
daily during TACE. Once the tumor is deemed resectable, patients proceed to surgery.

- Surgery: Patients undergo surgical resection of the tumor. Patients undergo either
partial or total hepatectomy followed by a liver transplant and lung surgery, if
necessary. Patients then proceed to the postoperative treatment.

- Postoperative treatment: Beginning within 6 weeks after surgery, patients receive oral
cyclophosphamide once every other day and oral thalidomide once daily for up to 1 year
in the absence of disease progression or unacceptable toxicity.

Patients with metastatic disease who show disease progression at any time during treatment
go off study and receive individual advice regarding further treatment based on the decision
of the principal investigator.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.