Intensive Neoadjuvant Chemotherapy in Treating Young Patients Undergoing Surgical Resection for High-Risk Hepatoblastoma
Recruitment status was Active, not recruiting
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.
Drug: doxorubicin hydrochloride
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intensified Pre-Operative Chemotherapy And Radical Surgery For High Risk Hepatoblastoma|
- Rate of complete remission after completion of study therapy [ Designated as safety issue: No ]
- Complete resection rate [ Designated as safety issue: No ]
- Response rate to preoperative chemotherapy [ Designated as safety issue: No ]
- Rate of grade 2 cardiac and renal, grade 3 otological, and grade 4 nonhematological toxicity as assessed during and after completion of study therapy [ Designated as safety issue: Yes ]
- Overall survival [ Designated as safety issue: No ]
- Event-free survival [ Designated as safety issue: No ]
|Study Start Date:||January 2004|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077389
|Institut Gustave Roussy|
|Villejuif, France, F-94805|
|Our Lady's Hospital for Sick Children Crumlin|
|Dublin, Ireland, 12|
|Amsterdam, Netherlands, NL-1100 DE|
|Birmingham Children's Hospital|
|Birmingham, England, United Kingdom, B4 6NH|
|Institute of Child Health at University of Bristol|
|Bristol, England, United Kingdom, BS2 8AE|
|Cambridge, England, United Kingdom, CB2 2QQ|
|Leeds Cancer Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS9 7TF|
|Leicester Royal Infirmary|
|Leicester, England, United Kingdom, LE1 5WW|
|Children's Cancer and Leukaemia Group|
|Leicester, England, United Kingdom, LE1 6TH|
|Royal Liverpool Children's Hospital, Alder Hey|
|Liverpool, England, United Kingdom, L12 2AP|
|Great Ormond Street Hospital for Children|
|London, England, United Kingdom, WC1N 3JH|
|London, England, United Kingdom, W1T 3AA|
|Royal Manchester Children's Hospital|
|Manchester, England, United Kingdom, M27 4HA|
|Sir James Spence Institute of Child Health at Royal Victoria Infirmary|
|Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP|
|Queen's Medical Centre|
|Nottingham, England, United Kingdom, NG7 2UH|
|Oxford Radcliffe Hospital|
|Oxford, England, United Kingdom, 0X3 9DU|
|Children's Hospital - Sheffield|
|Sheffield, England, United Kingdom, S10 2TH|
|Southampton General Hospital|
|Southampton, England, United Kingdom, SO16 6YD|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|Royal Belfast Hospital for Sick Children|
|Belfast, Northern Ireland, United Kingdom, BT12 6BE|
|Royal Aberdeen Children's Hospital|
|Aberdeen, Scotland, United Kingdom, AB25 2ZG|
|Royal Hospital for Sick Children|
|Edinburgh, Scotland, United Kingdom, EH9 1LF|
|Royal Hospital for Sick Children|
|Glasgow, Scotland, United Kingdom, G3 8SJ|
|Childrens Hospital for Wales|
|Cardiff, Wales, United Kingdom, CF14 4XW|
|Study Chair:||Margaret Childs||Children's Cancer and Leukaemia Group|