Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma
- Conditions
- Neuroblastoma
- Registration Number
- NCT00030719
- Lead Sponsor
- University of Leicester
- Brief Summary
RATIONALE: Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining isotretinoin and monoclonal antibodies may kill any remaining tumor cells following surgery. It is not yet known which treatment regimen is more effective in treating neuroblastoma.
PURPOSE: This randomized phase III trial is studying how well combination chemotherapy with or without filgrastim before surgery, high-dose chemotherapy, and radiation therapy followed by isotretinoin with or without monoclonal antibody work in treating patients with neuroblastoma.
- Detailed Description
OBJECTIVES:
* Compare the efficacy of myeloablative therapy with busulfan and melphalan vs carboplatin, etoposide, and melphalan, in terms of 3- and 5-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS), in patients with high-risk neuroblastoma.
* Compare the 3-year EFS in these patients treated with isotretinoin with or without monoclonal antibody Ch14.18 after myeloablative therapy.
* Determine the response at metastatic sites after induction chemotherapy in these patients.
* Determine the effect of metastatic disease response after induction chemotherapy on EFS, PFS, and OS in these patients.
* Compare the toxicity and episodes of febrile neutropenia in patients treated with induction chemotherapy with or without filgrastim (G-CSF).
* Determine the effect of elective hematopoietic support with G-CSF during induction chemotherapy on peripheral blood stem cell collection in these patients.
* Compare the acute and long-term toxic effects of the 2 myeloablative therapy regimens in these patients.
* Determine the effect of radiotherapy on pre-surgical tumor volume at the primary site on local control, EFS, PFS, and OS in these patients.
* Determine the tolerability of isotretinoin with or without monoclonal antibody Ch14.18 after myeloablative therapy in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (2 or 3 with MycN amplification vs 4). Patients are randomized to 1 of 8 treatment arms:
Arm I:
* Patients receive induction chemotherapy comprising vincristine IV, carboplatin IV over 1 hour, and etoposide IV over 4 hours on days 1 and 41; vincristine IV and cisplatin IV over 24 hours on days 11, 31, 51, and 71; and vincristine IV on days 21 and 61 and cyclophosphamide IV and etoposide over 4 hours on days 21, 22, 61, and 62. Patients receive filgrastim (G-CSF) subcutaneously on days 3-8, 12-18, 23-28, 32-38, 43-48, 52-58, 63-68, and 72 until peripheral blood stem cell (PBSC) collection.
* Patients undergo PBSC collection beginning on day 80. Patients then undergo surgery on day 95.
* Patients receive myeloablative therapy comprising oral busulfan 4 times daily on days -6 to -3 and melphalan IV over 15 minutes on day -2. Patients undergo PBSC infusion on day 0.
* Patients undergo radiotherapy in 14 fractions over 21 days.
* Beginning within 30 days after radiotherapy, patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for 6 courses.
Arm II:
* Patients receive induction chemotherapy as in arm I, but with no G-CSF. Patients then undergo PBSC collection and surgery as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm I. Patients undergo radiotherapy as in arm I.
* Patients receive oral isotretinoin twice daily on days 1-14 and monoclonal antibody Ch14.18 IV over 8 hours on days 1-5. Treatment repeats every 28 days for 6 courses for isotretinoin and every 28 days for 5 courses for monoclonal antibody Ch14.18.
Arm III:
* Patients receive induction chemotherapy and G-CSF as in arm I. Patients then undergo PBSC collection and surgery as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm I. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin as in arm I.
Arm IV:
* Patients receive induction chemotherapy as in arm II. Patients then undergo PBSC collection and surgery as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm I. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin and monoclonal antibody Ch14.18 as in arm II.
Arm V:
* Patients receive induction chemotherapy and G-CSF as in arm I.
* Patients receive myeloablative therapy comprising carboplatin IV continuously and etoposide IV continuously on days -7 to -4 and melphalan IV over 15 minutes on days -7 to -5. Patients undergo PBSC infusion on day 0.
* Patients undergo radiotherapy as in arm I. Patients receive isotretinoin as in arm I.
Arm VI:
* Patients receive induction chemotherapy as in arm II. Patients receive myeloablative therapy and undergo PBSC infusion as in arm V. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin and monoclonal antibody Ch14.18 as in arm II.
Arm VII:
* Patients receive induction chemotherapy and G-CSF as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm V. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin as in arm I.
Arm VIII:
* Patients receive induction chemotherapy as in arm II. Patients receive myeloablative therapy and undergo PBSC infusion as in arm V. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin and monoclonal antibody Ch14.18 as in arm II.
Patients on all treatment arms are followed every 6 months for 3 years and then annually for 2 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: Approximately 175 patients per year will be accrued for this study.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 175
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Event-free survival at 3 years Mean number of febrile events during induction
- Secondary Outcome Measures
Name Time Method Event-free survival at 5 years Overall survival Toxicity Response rate assessed by the International Neuroblastoma Response Criteria after 4 and 8 induction chemotherapy courses Biological factors (i.e., MycNM amplification, 1p deletion, ploidy, 17 q+, CD44, and Trk-A) Serum concentrations of lactic dehydrogenase, ferritin, neurone specific enolase Urinary catecholamines at diagnosis
Trial Locations
- Locations (31)
Universitair Ziekenhuis Gent
🇧🇪Ghent, Belgium
Rikshospitalet University Hospital
🇳🇴Oslo, Norway
Birmingham Children's Hospital
🇬🇧Birmingham, England, United Kingdom
Our Lady's Hospital for Sick Children Crumlin
🇮🇪Dublin, Ireland
Schneider Children's Medical Center of Israel
🇮🇱Petah-Tikva, Israel
Southampton General Hospital
🇬🇧Southampton, England, United Kingdom
Royal Aberdeen Children's Hospital
🇬🇧Aberdeen, Scotland, United Kingdom
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA
🇵🇹Lisbon, Portugal
Centre Hospitalier Universitaire Vaudois
🇨ðŸ‡Lausanne, Switzerland
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
Royal Liverpool Children's Hospital, Alder Hey
🇬🇧Liverpool, England, United Kingdom
Queen's Medical Centre
🇬🇧Nottingham, England, United Kingdom
Children's Hospital - Sheffield
🇬🇧Sheffield, England, United Kingdom
Sir James Spence Institute of Child Health at Royal Victoria Infirmary
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, England, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, England, United Kingdom
Middlesex Hospital
🇬🇧London, England, United Kingdom
Oxford Radcliffe Hospital
🇬🇧Oxford, England, United Kingdom
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Fondazione Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Aarhus Universitetshospital - Aarhus Sygehus
🇩🇰Aarhus, Denmark
Karolinska University Hospital - Solna
🇸🇪Stockholm, Sweden
St. Anna Children's Hospital
🇦🇹Vienna, Austria
Institut Gustave Roussy
🇫🇷Villejuif, France
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Institute of Child Health at University of Bristol
🇬🇧Bristol, England, United Kingdom
Childrens Hospital for Wales
🇬🇧Cardiff, Wales, United Kingdom
Royal Belfast Hospital for Sick Children
🇬🇧Belfast, Northern Ireland, United Kingdom
Royal Hospital for Sick Children
🇬🇧Glasgow, Scotland, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, England, United Kingdom