Ignite Creation Date:
2024-05-05 @ 5:15 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00410631
Status:
UNKNOWN
Last Update Posted:
2013-08-07
First Post:
2006-12-11
Brief Title:
Observation Combination Chemotherapy Radiation Therapy andor Autologous Stem Cell Transplant in Treating Young Patients With Neuroblastoma
Sponsor:
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
NB2004 Trial Protocol for Risk Adapted Treatment of Children With Neuroblastoma
Status:
UNKNOWN
Status Verified Date:
2008-01
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 Drugs used in chemotherapy work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Giving combination chemotherapy may kill more tumor cells Radiation therapy uses high-energy x-rays to kill tumor cells An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy This may allow more chemotherapy to be given so that more tumor cells are killed Sometimes after surgery the tumor may not need more treatment until it progresses In this case observation may be sufficient It is not yet known whether observation is more effective than combination chemotherapy radiation therapy andor autologous stem cell transplant in treating neuroblastoma
PURPOSE This randomized phase III and phase IV trial is studying observation combination chemotherapy radiation therapy andor autologous stem cell transplant to compare how well they work in treating young patients with neuroblastoma
PURPOSE This randomized phase III and phase IV trial is studying observation combination chemotherapy radiation therapy andor autologous stem cell transplant to compare how well they work in treating young patients with neuroblastoma
Detailed Description:
OBJECTIVES
Primary
Determine the event-free survival EFS of younger patients with newly diagnosed neuroblastoma categorized in the low-risk group LRG who undergo observation only or receive combination chemotherapy
Compare the EFS rate in patients with neuroblastoma categorized in the medium-risk group MRG treated with combination induction therapy maintenance therapy and consolidation therapy with that of a historical control group
Compare the EFS in patients with neuroblastoma categorized in the high-risk group HRG treated with standard vs experimental induction therapy followed by autologous stem cell transplantation and consolidation therapy
Secondary
Determine the locoregional EFS of patients in the LRG MRG or HRG
Determine the overall survival of these patients
Determine the extent of initial surgery the extent or impact of best surgery and surgery-related complications in these patients
Determine the time to transition to stage 4 disease in patients in the LRG or MRG
Determine the time to a locoregional event in patients in the LRG or HRG
Determine the time from diagnosis to an event in patients in the LRG
Determine the time from the beginning of regression to an adverse event in patients in the LRG
Determine the time to the beginning of primary tumor regression in patients in the LRG
Determine the time to the normalization of tumor markers in patients in the LRG
Determine the time to no evidence of disease in patients in the LRG with stage 4S disease
Assess the status of the primary tumor at 12 months and the best status of the primary tumor within 12 months in patients in the LRG
Determine the need for chemotherapy to control progression and the intensity of therapy required in patients in the LRG
Determine the acute and late side effects of external-beam radiotherapy in patients in the MRG or HRG
Determine the response to induction therapy in patients in the HRG
Assess early response after 2 courses of induction therapy in patients in the HRG
Determine the toxicity during induction courses 1 and 2 and the frequency of grade 3 or 4 toxicity during induction therapy in patients in the HRG
Assess the efficacy of iodine I 131 metaiodobenzylguanidine MIBG therapy in terms of activity and whole body dose in patients in the HRG
Assess molecular markers eg chromosome 1p chromosome 11q neuroblastoma gene chip in these patients
OUTLINE This is a prospective historically controlled randomized open-label multicenter study Patients are stratified according to disease risk low-risk vs medium-risk vs high-risk
Low-risk group Patients undergo complete staging 3 months after initial surgery Patients with no progression are observed for 12 months for patients over 1 year of age or until the end of the second year of life for patients 1 year of age or younger Patients with localized progression or threatening symptoms undergo N4 chemotherapy comprising doxorubicin hydrochloride IV over 30 minutes and vincristine IV on days 1 3 and 5 and cyclophosphamide IV over 30 minutes on days 1-7 Treatment repeats every 21 days for up to 4 courses Patients are reassessed after each course of N4 chemotherapy Patients achieving stable disease or tumor regression at any point discontinue N4 chemotherapy and undergo observation Patients with persistent progressive disease after 4 courses of N4 chemotherapy proceed to treatment as in the medium-risk group Patients who progress to stage 4 disease after initial surgery proceed to treatment as in the medium-risk group for patients 1 year of age or younger and no indication of stage 4S disease or high-risk group for patients over 1 year of age
Medium-risk group Patients receive induction therapy followed by maintenance therapy and consolidation therapy
Induction therapy Patients receive N5 chemotherapy comprising cisplatin IV continuously over 96 hours and etoposide phosphate IV continuously over 96 hours on days 1-4 vindesine IV over 1 hour on day 1 and filgrastim G-CSF subcutaneously SC 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 and ifosfamide IV continuously over 120 hours on days 1-5 doxorubicin hydrochloride IV over 4 hours on days 6 and 7 and G-CSF beginning on day 10 and continuing until blood counts recover Treatment repeats every 21 days alternating between N5 and N6 chemotherapy for up to 6 total courses 3 courses of N5 and N6 each Patients then proceed to maintenance therapy
NOTE Patients under 6 months of age receive up to 4 courses of N4 chemotherapy as in the low-risk group instead of N5N6 chemotherapy until they reach 6 months of age
Patients with active residual tumor after induction chemotherapy undergo external-beam radiotherapy EBRT for up to 25 fractions concurrently with maintenance chemotherapy Secondary surgery for resection of the primary tumor is attempted after course 4 or 6 of the induction therapy and before EBRT
Maintenance therapy Patients receive N7 chemotherapy comprising cyclophosphamide orally or IV over 1 hour on days 1-8 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity
Consolidation therapy Beginning 21 days after completion of maintenance therapy patients receive oral isotretinoin 2-3 times daily on days 1-14 Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity Patients then receive 3 additional courses after 3-months of rest
High-risk group Patients receive induction therapy followed by autologous stem cell transplantation ASCT and consolidation therapy
Induction therapy Patients 1 year of age and over are randomized to 1 of 2 treatment arms Patients under 1 year of age do not undergo randomization instead they are assigned to arm I
Arm I standard Patients receive N5 and N6 chemotherapy as in induction therapy for the medium-risk group
Arm II experimental Patients receive N8 chemotherapy comprising topotecan hydrochloride IV continuously over 168 hours and cyclophosphamide IV over 1 hour on days 1-7 etoposide IV over 1 hour on days 8-10 and G-CSF SC beginning on day 12 and continuing until blood counts recover Treatment repeats every 21 days for 2 courses Patients then receive N5 and N6 chemotherapy as in induction therapy for the medium-risk group
In both arms patients with active residual primary tumor after 6 courses of induction therapy undergo iodine I 131 metaiodobenzylguanidine MIBG radiotherapy before ASCT Patients also undergo EBRT for up to 25 fractions after ASCT Secondary surgery for resection of the primary tumor is attempted after course 4 or 6 of induction therapy and before radiotherapy
NOTE Patients under 6 months of age receive up to 4 courses of N4 chemotherapy as in the low-risk group instead of N5N6 chemotherapy until they reach 6 months of age
NOTE Patients with MIBG-negative disease undergo EBRT only
Conditioning followed by 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 ASCT on day 0 Patients receive G-CSF SC beginning on day 2 and continuing until blood counts recover
Consolidation therapy Beginning 30 days after ASCT patients receive isotretinoin as in consolidation therapy for the medium-risk group
NOTE Isotretinoin is discontinued during EBRT and restarted 1 week after completion of EBRT
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 642 patients will be accrued for this study
Primary
Determine the event-free survival EFS of younger patients with newly diagnosed neuroblastoma categorized in the low-risk group LRG who undergo observation only or receive combination chemotherapy
Compare the EFS rate in patients with neuroblastoma categorized in the medium-risk group MRG treated with combination induction therapy maintenance therapy and consolidation therapy with that of a historical control group
Compare the EFS in patients with neuroblastoma categorized in the high-risk group HRG treated with standard vs experimental induction therapy followed by autologous stem cell transplantation and consolidation therapy
Secondary
Determine the locoregional EFS of patients in the LRG MRG or HRG
Determine the overall survival of these patients
Determine the extent of initial surgery the extent or impact of best surgery and surgery-related complications in these patients
Determine the time to transition to stage 4 disease in patients in the LRG or MRG
Determine the time to a locoregional event in patients in the LRG or HRG
Determine the time from diagnosis to an event in patients in the LRG
Determine the time from the beginning of regression to an adverse event in patients in the LRG
Determine the time to the beginning of primary tumor regression in patients in the LRG
Determine the time to the normalization of tumor markers in patients in the LRG
Determine the time to no evidence of disease in patients in the LRG with stage 4S disease
Assess the status of the primary tumor at 12 months and the best status of the primary tumor within 12 months in patients in the LRG
Determine the need for chemotherapy to control progression and the intensity of therapy required in patients in the LRG
Determine the acute and late side effects of external-beam radiotherapy in patients in the MRG or HRG
Determine the response to induction therapy in patients in the HRG
Assess early response after 2 courses of induction therapy in patients in the HRG
Determine the toxicity during induction courses 1 and 2 and the frequency of grade 3 or 4 toxicity during induction therapy in patients in the HRG
Assess the efficacy of iodine I 131 metaiodobenzylguanidine MIBG therapy in terms of activity and whole body dose in patients in the HRG
Assess molecular markers eg chromosome 1p chromosome 11q neuroblastoma gene chip in these patients
OUTLINE This is a prospective historically controlled randomized open-label multicenter study Patients are stratified according to disease risk low-risk vs medium-risk vs high-risk
Low-risk group Patients undergo complete staging 3 months after initial surgery Patients with no progression are observed for 12 months for patients over 1 year of age or until the end of the second year of life for patients 1 year of age or younger Patients with localized progression or threatening symptoms undergo N4 chemotherapy comprising doxorubicin hydrochloride IV over 30 minutes and vincristine IV on days 1 3 and 5 and cyclophosphamide IV over 30 minutes on days 1-7 Treatment repeats every 21 days for up to 4 courses Patients are reassessed after each course of N4 chemotherapy Patients achieving stable disease or tumor regression at any point discontinue N4 chemotherapy and undergo observation Patients with persistent progressive disease after 4 courses of N4 chemotherapy proceed to treatment as in the medium-risk group Patients who progress to stage 4 disease after initial surgery proceed to treatment as in the medium-risk group for patients 1 year of age or younger and no indication of stage 4S disease or high-risk group for patients over 1 year of age
Medium-risk group Patients receive induction therapy followed by maintenance therapy and consolidation therapy
Induction therapy Patients receive N5 chemotherapy comprising cisplatin IV continuously over 96 hours and etoposide phosphate IV continuously over 96 hours on days 1-4 vindesine IV over 1 hour on day 1 and filgrastim G-CSF subcutaneously SC 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 and ifosfamide IV continuously over 120 hours on days 1-5 doxorubicin hydrochloride IV over 4 hours on days 6 and 7 and G-CSF beginning on day 10 and continuing until blood counts recover Treatment repeats every 21 days alternating between N5 and N6 chemotherapy for up to 6 total courses 3 courses of N5 and N6 each Patients then proceed to maintenance therapy
NOTE Patients under 6 months of age receive up to 4 courses of N4 chemotherapy as in the low-risk group instead of N5N6 chemotherapy until they reach 6 months of age
Patients with active residual tumor after induction chemotherapy undergo external-beam radiotherapy EBRT for up to 25 fractions concurrently with maintenance chemotherapy Secondary surgery for resection of the primary tumor is attempted after course 4 or 6 of the induction therapy and before EBRT
Maintenance therapy Patients receive N7 chemotherapy comprising cyclophosphamide orally or IV over 1 hour on days 1-8 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity
Consolidation therapy Beginning 21 days after completion of maintenance therapy patients receive oral isotretinoin 2-3 times daily on days 1-14 Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity Patients then receive 3 additional courses after 3-months of rest
High-risk group Patients receive induction therapy followed by autologous stem cell transplantation ASCT and consolidation therapy
Induction therapy Patients 1 year of age and over are randomized to 1 of 2 treatment arms Patients under 1 year of age do not undergo randomization instead they are assigned to arm I
Arm I standard Patients receive N5 and N6 chemotherapy as in induction therapy for the medium-risk group
Arm II experimental Patients receive N8 chemotherapy comprising topotecan hydrochloride IV continuously over 168 hours and cyclophosphamide IV over 1 hour on days 1-7 etoposide IV over 1 hour on days 8-10 and G-CSF SC beginning on day 12 and continuing until blood counts recover Treatment repeats every 21 days for 2 courses Patients then receive N5 and N6 chemotherapy as in induction therapy for the medium-risk group
In both arms patients with active residual primary tumor after 6 courses of induction therapy undergo iodine I 131 metaiodobenzylguanidine MIBG radiotherapy before ASCT Patients also undergo EBRT for up to 25 fractions after ASCT Secondary surgery for resection of the primary tumor is attempted after course 4 or 6 of induction therapy and before radiotherapy
NOTE Patients under 6 months of age receive up to 4 courses of N4 chemotherapy as in the low-risk group instead of N5N6 chemotherapy until they reach 6 months of age
NOTE Patients with MIBG-negative disease undergo EBRT only
Conditioning followed by 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 ASCT on day 0 Patients receive G-CSF SC beginning on day 2 and continuing until blood counts recover
Consolidation therapy Beginning 30 days after ASCT patients receive isotretinoin as in consolidation therapy for the medium-risk group
NOTE Isotretinoin is discontinued during EBRT and restarted 1 week after completion of EBRT
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 642 patients will be accrued for this study
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 |
| CDR0000517312 | REGISTRY | None | None |