Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Amifostine in Treating Young Patients With Liver Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	21 and under	NCI	COG-P9645 POG-9645, CCG-P9645, NCT00003994, P9645

Objectives

1. Determine the event-free survival rate in children with stage III or IV unresectable or metastatic hepatoblastoma treated with cisplatin, vincristine, and fluorouracil (stages III and IV closed to accrual as of 11-25-03).
2. Evaluate the efficacy of amifostine* in reducing toxicity associated with platinum agents in patients with hepatoblastoma.
3. Determine whether amifostine* effects event-free survival in these patients in response to these regimens.
4. Evaluate the event-free survival in patients with stage I pure fetal histology treated with surgery alone.
5. Evaluate the efficacy of amifostine* in reducing toxicity associated with cisplatin in patients with resected tumors.
6. Determine the response in patients treated with amifostine* in combination with these regimens.

 [Note: * Arm II (amifostine) closed to accrual as of 11-25-03; arm IV (amifostine) closed to accrual as of 4-5-02]

Entry Criteria

Disease Characteristics:

• Histologically proven hepatoblastoma
  • Any stage allowed (stages II-IV closed to accrual as of 11-25-03)
• Stratum 1 (stage I):
  • Pure fetal histology
  • Complete surgical resection of tumor
• Stratum 2 (stages I or II) (stage II closed to accrual as of 11-25-03), meeting 1 of the following criteria:
  • Complete resection of tumor with histology other than pure fetal
  • Gross resection of tumor, including resected tumors with preoperative/intraoperative rupture
• Stratum 3 (stages III or IV) (stages III and IV closed to accrual as of 11-25-03), meeting 1 of the following criteria:
  • Unresectable tumors
    • Partial resection of tumor with measurable residual disease OR lymph node involvement
  • Measurable metastatic disease to lungs or other organs
• No hepatocellular carcinoma

Prior/Concurrent Therapy:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No prior endocrine therapy

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior therapy except tumor resection

Patient Characteristics:

Age:

• 21 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Creatinine normal for age

  OR

• Glomerular filtration rate normal for age

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

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

Outcomes

Response
Toxicity
Event-free survival
Efficacy

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.

Katzenstein HM, Chang KW, Krailo M, et al.: Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma: a report of the Intergroup Hepatoblastoma Study P9645 as a part of the Children's Oncology Group. Cancer : , 2009.[PUBMED Abstract]

Malogolowkin MH, Katzenstein H, Krailo MD, et al.: Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma. J Clin Oncol 24 (18): 2879-84, 2006.[PUBMED Abstract]

Malogolowkin MH, Katzenstein HM, Krailo MD, et al.: Complete surgical resection for children with pure fetal histology hepatoblastoma (PFH): A report of the Childrens Oncology Group. [Abstract] J Clin Oncol 26 (Suppl 15): A-10049, 2008.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Howard Katzenstein, MD, Protocol chair		Ph: 404-785-0853 Email: howard.katzenstein@choa.org

Registry Information
Official Title		Intergroup Protocol for Treatment of Children with Hepatoblastoma
Trial Start Date		1993-03-15
Trial Completion Date		2007-10-01
Registered in ClinicalTrials.gov		NCT00003994
Date Submitted to PDQ		1999-07-01
Information Last Verified		2006-11-18
NCI Grant/Contract Number		CA30969

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