Intensive Neoadjuvant Chemotherapy in Treating Young Patients Undergoing Surgical Resection for High-Risk Hepatoblastoma
23. juni 2014 opdateret af: University of Leicester
Intensified Pre-Operative Chemotherapy And Radical Surgery For High Risk Hepatoblastoma
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.
Studieoversigt
Status
Ukendt
Betingelser
Detaljeret beskrivelse
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.
Undersøgelsestype
Interventionel
Tilmelding (Forventet)
57
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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England
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Birmingham, England, Det Forenede Kongerige, B4 6NH
- Birmingham Children's Hospital
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Bristol, England, Det Forenede Kongerige, BS2 8AE
- Institute of Child Health at University of Bristol
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Cambridge, England, Det Forenede Kongerige, CB2 2QQ
- Addenbrooke's Hospital
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Leeds, England, Det Forenede Kongerige, LS9 7TF
- Leeds Cancer Centre at St. James's University Hospital
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Leicester, England, Det Forenede Kongerige, LE1 5WW
- Leicester Royal Infirmary
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Leicester, England, Det Forenede Kongerige, LE1 6TH
- Children's Cancer and Leukaemia Group
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Liverpool, England, Det Forenede Kongerige, L12 2AP
- Royal Liverpool Children's Hospital, Alder Hey
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London, England, Det Forenede Kongerige, W1T 3AA
- Middlesex Hospital
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London, England, Det Forenede Kongerige, WC1N 3JH
- Great Ormond Street Hospital For Children
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Manchester, England, Det Forenede Kongerige, M27 4HA
- Royal Manchester Children's Hospital
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Newcastle-Upon-Tyne, England, Det Forenede Kongerige, NE1 4LP
- Sir James Spence Institute of Child Health at Royal Victoria Infirmary
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Nottingham, England, Det Forenede Kongerige, NG7 2UH
- Queen's Medical Centre
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Oxford, England, Det Forenede Kongerige, 0X3 9DU
- Oxford Radcliffe Hospital
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Sheffield, England, Det Forenede Kongerige, S10 2TH
- Children's Hospital - Sheffield
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Southampton, England, Det Forenede Kongerige, SO16 6YD
- Southampton General Hospital
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Sutton, England, Det Forenede Kongerige, SM2 5PT
- Royal Marsden - Surrey
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Northern Ireland
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Belfast, Northern Ireland, Det Forenede Kongerige, BT12 6BE
- Royal Belfast Hospital for Sick Children
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Scotland
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Aberdeen, Scotland, Det Forenede Kongerige, AB25 2ZG
- Royal Aberdeen Children's Hospital
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Edinburgh, Scotland, Det Forenede Kongerige, EH9 1LF
- Royal Hospital for Sick Children
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Glasgow, Scotland, Det Forenede Kongerige, G3 8SJ
- Royal Hospital for Sick Children
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Wales
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Cardiff, Wales, Det Forenede Kongerige, CF14 4XW
- Childrens Hospital for Wales
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Villejuif, Frankrig, F-94805
- Institut Gustave Roussy
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Amsterdam, Holland, NL-1100 DE
- Emma Kinderziekenhuis
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Dublin, Irland, 12
- Our Lady's Hospital for Sick Children Crumlin
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
Ikke ældre end 17 år (Barn)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Maskning: Ingen (Åben etiket)
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
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Rate of complete remission after completion of study therapy
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Sekundære resultatmål
Resultatmål |
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Samlet overlevelse
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Begivenhedsfri overlevelse
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Fuldstændig resektionsrate
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Response rate to preoperative chemotherapy
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Rate of grade 2 cardiac and renal, grade 3 otological, and grade 4 nonhematological toxicity as assessed during and after completion of study therapy
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Studiestol: Margaret Childs, Children's Cancer and Leukaemia Group
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. doi: 10.1016/S1470-2045(13)70272-9. Epub 2013 Jul 4.
- Weeda VB, Murawski M, McCabe AJ, Maibach R, Brugieres L, Roebuck D, Fabre M, Zimmermann A, Otte JB, Sullivan M, Perilongo G, Childs M, Brock P, Zsiros J, Plaschkes J, Czauderna P, Aronson DC. Fibrolamellar variant of hepatocellular carcinoma does not have a better survival than conventional hepatocellular carcinoma--results and treatment recommendations from the Childhood Liver Tumour Strategy Group (SIOPEL) experience. Eur J Cancer. 2013 Aug;49(12):2698-704. doi: 10.1016/j.ejca.2013.04.012. Epub 2013 May 15.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. januar 2004
Datoer for studieregistrering
Først indsendt
10. februar 2004
Først indsendt, der opfyldte QC-kriterier
11. februar 2004
Først opslået (Skøn)
12. februar 2004
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
24. juni 2014
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
23. juni 2014
Sidst verificeret
1. december 2009
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Neoplasmer efter sted
- Neoplasmer i fordøjelsessystemet
- Leversygdomme
- Neoplasmer, komplekse og blandede
- Neoplasmer i leveren
- Hepatoblastom
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Topoisomerase II-hæmmere
- Topoisomerasehæmmere
- Antibiotika, antineoplastisk
- Carboplatin
- Doxorubicin
- Liposomal doxorubicin
Andre undersøgelses-id-numre
- CDR0000350221
- SIOP-SIOPEL-4
- EU-20336
- CCLG-LT-2004-09
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .