Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active Under 18 Other SIOP-SIOPEL-4 EU-20336, CCLG-LT-2004-09, NCT00077389

Objectives

Primary

1. Determine the efficacy and short-term toxicity of intensified neoadjuvant chemotherapy in children with high-risk hepatoblastoma undergoing surgical resection.
2. 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.
3. Determine, prospectively, the role of this regimen in rendering unresectable tumors resectable in these patients.
4. Determine the accuracy of initial imaging in predicting the surgical options (after treatment with this regimen) for patients presenting with unresectable disease.

Secondary

1. Determine the overall survival and event-free survival of patients treated with this regimen (with an acceptable overall toxicity).
2. Determine the toxicity of this regimen in these patients.
3. Determine the response rate in patients treated with this regimen.
4. Determine whether response to this regimen, defined by the modified RECIST criteria, can be used for better monitoring of response in these patients.
5. Determine whether a fall in alpha-fetoprotein during this neoadjuvant regimen can be used as a prognostic factor in these patients.
6. 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.

Entry Criteria

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

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

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

Expected Enrollment

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

Outcomes

Rate of complete remission after completion of study therapy

Complete resection rate
Response rate to preoperative chemotherapy
Rate of grade 2 cardiac and renal, grade 3 otological, and grade 4 nonhematological toxicity as assessed during and after completion of study therapy
Overall survival
Event-free survival

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

Trial Contact Information

Trial Lead Organizations

University Hospitals of Leicester NHS Trust

Margaret Childs, Protocol chair		Ph: 44-0115-252-2380

France
	Villejuif
	Institut Gustave Roussy
		Laurence Brugieres, MD	Ph:  33-1-4211-4180
Ireland
	Dublin
	Our Lady's Hospital for Sick Children Crumlin
		Fin Breatnach, MD, FRCPE	Ph:  353-1-409-6659
			Email: fin.breatnach@olhsc.ie
Netherlands
	Amsterdam
	Emma Kinderziekenhuis
		Jozsef Zsiros, MD, PhD	Ph:  31-20-566-9111
			Email: j.zsiros@amc.uva.nl
United Kingdom
England
	Birmingham
	Birmingham Children's Hospital
		Martin English, MD	Ph:  44-121-333-8412
			Email: martin.english@bch.nhs.uk
	Bristol
	Institute of Child Health at University of Bristol
		Pamela Kearns, MD	Ph:  44-117-342-0205
	Cambridge
	Addenbrooke's Hospital
		Amos Burke, MD	Ph:  44-1223-348-151
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
		Adam Glaser, MD	Ph:  44-113-206-4984
			Email: adam.glaser@leedsth.nhs.uk
	Leicester
	Children's Cancer and Leukaemia Group
		Margaret Childs	Ph:  44-0115-252-2380
	Leicester Royal Infirmary
		Mabrouk Madi, MD	Ph:  44-116-258-5959
	Liverpool
	Royal Liverpool Children's Hospital, Alder Hey
		Heather McDowell, MD	Ph:  44-151-293-3679
	London
	Great Ormond Street Hospital for Children
		Penelope Brock, MD, PhD	Ph:  44-20-829-8832
			Email: Brockp@gosh.nhs.uk
	Middlesex Hospital
		Ananth Shankar, MD	Ph:  44-20-7380-9300 ext. 9950
	Manchester
	Royal Manchester Children's Hospital
		Bernadette Brennan, MD	Ph:  44-161-922-2227
			Email: bernadette.brennan@cmmc.nhs.uk
	Newcastle-Upon-Tyne
	Sir James Spence Institute of Child Health
		Juliet Hale, MD	Ph:  44-191-282-4101
			Email: j.p.hale@ncl.ac.uk
	Nottingham
	Queen's Medical Centre
		Martin Hewitt, MD, BSc, FRCP, FRCPCH	Ph:  44-115-924-9924 ext. 63394
			Email: martin.hewitt@nuh.nhs.uk
	Oxford
	Oxford Radcliffe Hospital
		Kate Wheeler, MD	Ph:  44-186-522-1066
	Sheffield
	Children's Hospital - Sheffield
		Mary Gerrard, BSc, MBChB, FRCP, FRCPCH	Ph:  44-114-271-7366
			Email: mary.gerrard@sch.nhs.uk
	Southampton
	Southampton General Hospital
		Janice Kohler, MD, FRCP	Ph:  44-23-8079-6942
	Sutton
	Royal Marsden - Surrey
		Mary Taj, MD	Ph:  44-20-8642-6011 ext. 3089
Northern Ireland
	Belfast
	Royal Belfast Hospital for Sick Children
		Anthony McCarthy, MD	Ph:  44-289-063-3631
			Email: anthonymcarthy@royalhospital.n.i.nhs.uk
Scotland
	Aberdeen
	Royal Aberdeen Children's Hospital
		Veronica Neefjes	Ph:  44-1224-550-217
	Edinburgh
	Royal Hospital for Sick Children
		W. Hamish Wallace, MD	Ph:  44-131-536-0426
	Glasgow
	Royal Hospital for Sick Children
		Milind Ronghe, MD	Ph:  44-141-201-9309
Wales
	Cardiff
	Childrens Hospital for Wales
		Heidi Traunecker, MD, PhD	Ph:  44-29-2074-2285
			Email: heidi.traunecker@cardiffandvale.wales.nhs.uk

Registry Information
Official Title		Intensified Pre-Operative Chemotherapy And Radical Surgery For High Risk Hepatoblastoma
Trial Start Date		2004-01-09
Registered in ClinicalTrials.gov		NCT00077389
Date Submitted to PDQ		2003-12-22
Information Last Verified		2007-07-17

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