Ignite Creation Date:
2024-05-05 @ 6:41 PM
Last Modification Date:
2024-10-26 @ 9:36 AM
Study NCT ID:
NCT00526318
Status:
UNKNOWN
Last Update Posted:
2015-07-16
First Post:
2007-09-05
Brief Title:
Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-Risk Neuroblastoma
Sponsor:
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Trial Protocol for the Treatment of Children With High Risk Neuroblastoma NB2004-HR
Status:
UNKNOWN
Status Verified Date:
2015-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or by killing them It also prepares the patients bone marrow for the stem cell transplant The stem cells are given to the patient to replace the blood-forming cells that were destroyed by the chemotherapy Giving isotretinoin after transplant may kill any remaining tumor cells It is not yet known which combination chemotherapy regimen is more effective when given before a stem cell transplant and isotretinoin in treating neuroblastoma
PURPOSE This randomized clinical trial is studying two different combination chemotherapy regimens to compare how well they work when given before a stem cell transplant and isotretinoin in treating young patients with high-risk neuroblastoma
PURPOSE This randomized clinical trial is studying two different combination chemotherapy regimens to compare how well they work when given before a stem cell transplant and isotretinoin in treating young patients with high-risk neuroblastoma
Detailed Description:
OBJECTIVES
Primary
Compare the event-free survival of pediatric patients with high-risk neuroblastoma treated with standard induction chemotherapy vs topotecan hydrochloride-containing induction chemotherapy followed by myeloablative autologous stem cell transplantation and consolidation therapy with isotretinoin
Secondary
Compare the overall survival of patients treated with these regimens
Compare early response complete response very good partial response partial response mixed response stable disease and progressionrelapse after 2 courses of standard vs experimental induction chemotherapy or after 60 days if the second course is not yet finished
Compare response to standard vs experimental induction chemotherapy before autologous stem cell transplantation or after 280 days if induction chemotherapy is not yet finished
Compare the toxicity of standard vs experimental induction chemotherapy during courses 1 and 2 and the frequency of grade 3 toxicity during the last 6 courses of induction chemotherapy
Compare the extent of initial surgery and best surgery biopsy vs incomplete resection vs macroscopic complete resection and the frequency of complications related to surgery eg nephrectomy bleeding infection or intestinal obstruction
Compare the acute and long-term side effects of external-beam radiotherapy
Correlate the activity of MIBG and whole-body radiation dose
Collect and store tumor material in the tumor bank for future evaluation of other molecular markers MYCN and status of chromosome 1p and 11q and prognostic significant gene signatures
OUTLINE This is a multicenter study Patients are stratified according to disease stage lactate dehydrogenase LDH status MYCN status and age at diagnosis stage 4 disease LDH not elevated any MYCN status age at diagnosis 1-21 years vs stage 4 disease LDH elevated any MYCN status age at diagnosis 1 but 2 years vs stage 4 disease LDH elevated any MYCN status age at diagnosis 2-21 years vs localized disease MYCN amplification age at diagnosis 6 months
Induction chemotherapy Patients are randomized to 1 of 2 induction chemotherapy arms
Arm I standard Patients receive N5 chemotherapy comprising cisplatin IV continuously over 96 hours and etoposide phosphate IV continuously over 96 hours on days 1-4 and vindesine IV over 1 hour on day 1 Patients also receive filgrastim G-CSF subcutaneously SC once daily beginning on day 9 and continuing until blood counts recover Patients then receive N6 chemotherapy comprising vincristine IV over 1 hour on days 1 and 8 dacarbazine IV over 1 hour on days 1-5 ifosfamide IV continuously over 120 hours on days 1-5 and doxorubicin hydrochloride IV over 4 hours on days 6 and 7 Patients also receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover Treatment with N5 and N6 chemotherapy alternates every 21 days for 6 courses N5 chemotherapy is given in courses 1 3 and 5 and N6 chemotherapy is given in courses 2 4 and 6
Arm II experimental Patients receive N8 chemotherapy comprising cyclophosphamide IV over 1 hour on days 1-7 topotecan hydrochloride IV continuously over 168 hours on days 1-7 and etoposide phosphate IV over 1 hour on days 8-10 Patients also receive G-CSF SC once daily beginning on day 12 and continuing until blood counts recover Treatment with N8 chemotherapy repeats every 21 days for 2 courses Patients then receive N5 chemotherapy alternating with N6 chemotherapy as in arm I
Surgery Patients may undergo secondary surgery after completion of 4 or 6 courses of induction chemotherapy but prior to radiotherapy
Radiotherapy 131I-MIBG therapy and external-beam radiotherapy EBRT Patients with active residual primary tumor after the completion of induction chemotherapy undergo 131I-MIBG therapy prior to autologous stem cell transplantation ASCT and EBRT after ASCT
NOTE Patients with MIBG negative neuroblastoma at initial diagnosis will only receive EBRT
Myeloablative ASCT Patients receive melphalan IV over 30 minutes on days -8 to -5 etoposide phosphate IV over 4 hours on day -4 and carboplatin IV over 1 hour on days -4 to -2 Patients undergo reinfusion of CD34 stem cells on day 0 Patients also receive G-CSF SC or IV over 4 hours once daily beginning on day 2 and continuing until blood counts recover
Consolidation therapy isotretinoin Beginning 30 days after ASCT patients receive oral isotretinoin once daily on days 1-14 Treatment repeats every 28 days for up to 6 courses Beginning 3 months later patients receive an additional 3 courses of isotretinoin
NOTE Isotretinoin must not be given concurrently with radiotherapy
After completion of study treatment patients are followed every 6 weeks for 1 year every 3 months for 4 years and then every 6 months thereafter
Primary
Compare the event-free survival of pediatric patients with high-risk neuroblastoma treated with standard induction chemotherapy vs topotecan hydrochloride-containing induction chemotherapy followed by myeloablative autologous stem cell transplantation and consolidation therapy with isotretinoin
Secondary
Compare the overall survival of patients treated with these regimens
Compare early response complete response very good partial response partial response mixed response stable disease and progressionrelapse after 2 courses of standard vs experimental induction chemotherapy or after 60 days if the second course is not yet finished
Compare response to standard vs experimental induction chemotherapy before autologous stem cell transplantation or after 280 days if induction chemotherapy is not yet finished
Compare the toxicity of standard vs experimental induction chemotherapy during courses 1 and 2 and the frequency of grade 3 toxicity during the last 6 courses of induction chemotherapy
Compare the extent of initial surgery and best surgery biopsy vs incomplete resection vs macroscopic complete resection and the frequency of complications related to surgery eg nephrectomy bleeding infection or intestinal obstruction
Compare the acute and long-term side effects of external-beam radiotherapy
Correlate the activity of MIBG and whole-body radiation dose
Collect and store tumor material in the tumor bank for future evaluation of other molecular markers MYCN and status of chromosome 1p and 11q and prognostic significant gene signatures
OUTLINE This is a multicenter study Patients are stratified according to disease stage lactate dehydrogenase LDH status MYCN status and age at diagnosis stage 4 disease LDH not elevated any MYCN status age at diagnosis 1-21 years vs stage 4 disease LDH elevated any MYCN status age at diagnosis 1 but 2 years vs stage 4 disease LDH elevated any MYCN status age at diagnosis 2-21 years vs localized disease MYCN amplification age at diagnosis 6 months
Induction chemotherapy Patients are randomized to 1 of 2 induction chemotherapy arms
Arm I standard Patients receive N5 chemotherapy comprising cisplatin IV continuously over 96 hours and etoposide phosphate IV continuously over 96 hours on days 1-4 and vindesine IV over 1 hour on day 1 Patients also receive filgrastim G-CSF subcutaneously SC once daily beginning on day 9 and continuing until blood counts recover Patients then receive N6 chemotherapy comprising vincristine IV over 1 hour on days 1 and 8 dacarbazine IV over 1 hour on days 1-5 ifosfamide IV continuously over 120 hours on days 1-5 and doxorubicin hydrochloride IV over 4 hours on days 6 and 7 Patients also receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover Treatment with N5 and N6 chemotherapy alternates every 21 days for 6 courses N5 chemotherapy is given in courses 1 3 and 5 and N6 chemotherapy is given in courses 2 4 and 6
Arm II experimental Patients receive N8 chemotherapy comprising cyclophosphamide IV over 1 hour on days 1-7 topotecan hydrochloride IV continuously over 168 hours on days 1-7 and etoposide phosphate IV over 1 hour on days 8-10 Patients also receive G-CSF SC once daily beginning on day 12 and continuing until blood counts recover Treatment with N8 chemotherapy repeats every 21 days for 2 courses Patients then receive N5 chemotherapy alternating with N6 chemotherapy as in arm I
Surgery Patients may undergo secondary surgery after completion of 4 or 6 courses of induction chemotherapy but prior to radiotherapy
Radiotherapy 131I-MIBG therapy and external-beam radiotherapy EBRT Patients with active residual primary tumor after the completion of induction chemotherapy undergo 131I-MIBG therapy prior to autologous stem cell transplantation ASCT and EBRT after ASCT
NOTE Patients with MIBG negative neuroblastoma at initial diagnosis will only receive EBRT
Myeloablative ASCT Patients receive melphalan IV over 30 minutes on days -8 to -5 etoposide phosphate IV over 4 hours on day -4 and carboplatin IV over 1 hour on days -4 to -2 Patients undergo reinfusion of CD34 stem cells on day 0 Patients also receive G-CSF SC or IV over 4 hours once daily beginning on day 2 and continuing until blood counts recover
Consolidation therapy isotretinoin Beginning 30 days after ASCT patients receive oral isotretinoin once daily on days 1-14 Treatment repeats every 28 days for up to 6 courses Beginning 3 months later patients receive an additional 3 courses of isotretinoin
NOTE Isotretinoin must not be given concurrently with radiotherapy
After completion of study treatment patients are followed every 6 weeks for 1 year every 3 months for 4 years and then every 6 months thereafter
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EU-20661 | Registry Identifier | PDQ Physician Data Query | None |
| CDR0000564820 | REGISTRY | None | None |
| UNI-KOELN-161 | None | None | None |