Intensive Neoadjuvant Chemotherapy in Treating Young Patients Undergoing Surgical Resection for High-Risk Hepatoblastoma

Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00077389
• Other study ID #: CDR0000350221
• Secondary ID: SIOP-SIOPEL-4EU-
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 10, 2004
• Last updated: June 23, 2014
• Start date: January 2004

Study information

• Verified date: December 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy drugs before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well neoadjuvant chemotherapy works in treating young patients who are undergoing surgical resection for high-risk hepatoblastoma.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 57
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatoblastoma

• High-risk disease, meeting criteria for at least 1 of the following:

• Tumor involving all 4 hepatic sections

• Evidence of abdominal extrahepatic disease

• Presence of metastases

• Alpha-fetoprotein < 100 ng/mL at diagnosis

• Must have had a prior diagnostic biopsy within the past 15 days

• No recurrent disease

PATIENT CHARACTERISTICS:

Age

• Under 18

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• AST and/or ALT = 3 times normal

Renal

• Glomerular filtration rate = 60 mL/min

Cardiovascular

• Shortening fraction = 29% OR

• Ejection fraction = 40%

Other

• Not pregnant

• Negative pregnancy test

• No pre-existing clinically relevant bilateral hearing loss

• No other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for hepatoblastoma

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatoblastoma
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• carboplatin

• cisplatin

• doxorubicin hydrochloride

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
Netherlands	Emma Kinderziekenhuis	Amsterdam
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Institute of Child Health at University of Bristol	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Children's Cancer and Leukaemia Group	Leicester	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	Middlesex Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
University of Leicester

Countries where clinical trial is conducted

France,  Ireland,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete remission after completion of study therapy			No
Secondary	Complete resection rate			No
Secondary	Response rate to preoperative chemotherapy			No
Secondary	Rate of grade 2 cardiac and renal, grade 3 otological, and grade 4 nonhematological toxicity as assessed during and after completion of study therapy			Yes
Secondary	Overall survival			No
Secondary	Event-free survival			No