Last updated on June 2014

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


Brief description of study

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 Study 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.

Clinical Study Identifier: NCT00030719

Contact Investigators or Research Sites near you

Start Over

Henrik Schroder, MD

Aarhus Universitetshospital - Aarhus Sygehus
Aarhus, Denmark
  Connect »

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


Receive Emails About New Clinical Trials!

Sign up for our FREE service to receive email notifications when clinical trials are posted in the medical category of interest to you.