Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00040872
Status:
COMPLETED
Last Update Posted:
2013-03-07
First Post:
2002-07-08
Brief Title:
Multiple Therapies in Treating Patients With Advanced Neuroblastoma
Sponsor:
Memorial Sloan Kettering Cancer Center
Organization:
Memorial Sloan Kettering Cancer Center
Study Overview
Official Title:
N8 Dose-Intensive Chemotherapy Plus Biologics in the Treatment of Neuroblastoma
Status:
COMPLETED
Status Verified Date:
2013-03
Last Known Status:
None
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 use different ways to stop tumor cells from dividing so they stop growing or die Combining chemotherapy with peripheral stem cell transplantation 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 Radiation therapy uses high-energy x-rays to damage tumor cells Biological therapies use different ways to stimulate the immune system and stop cancer cell from growing Combining different types of therapies may kill more tumor cells
PURPOSE Phase II trial to study the effectiveness of combining chemotherapy monoclonal antibody therapy surgery peripheral stem cell transplantation radiation therapy and biological therapy in treating patients who have advanced neuroblastoma
PURPOSE Phase II trial to study the effectiveness of combining chemotherapy monoclonal antibody therapy surgery peripheral stem cell transplantation radiation therapy and biological therapy in treating patients who have advanced neuroblastoma
Detailed Description:
OBJECTIVES
Determine whether treatment with multimodality therapy comprising dose-intensive induction chemotherapy monoclonal antibody 3F8 surgery myeloablative chemotherapy autologous or syngeneic bone marrow or peripheral blood stem cell transplantation radiotherapy and isotretinoin improves the cure rate in patients with advanced neuroblastoma
Determine whether the 2-year progression-free survival PFS rate improves to 70 in patients with newly diagnosed advanced neuroblastoma treated with this regimen
Determine whether the 2-year PFS rate improves to 40 in patients with previously treated advanced neuroblastoma treated with this regimen
Determine the biologic and clinical prognostic factors of neuroblastoma that may guide future research of treatment approaches for this malignancy
OUTLINE Patients are stratified according to the following
Stratum 1 Patients with previously untreated stage IV disease who are over age 1 at diagnosis with or without N-myc amplification
Stratum 2 Patients with previously treated stage IV disease who are over age 1 at diagnosis or patients with previously treated high-risk disease eg N-myc amplified stage III or IV disease under age 1 at diagnosis and with or without prior treatment
Intensive induction therapy courses 1-5 During courses 1 2 and 4 patients receive cyclophosphamide IV over 6 hours on days 1 and 2 and doxorubicin and vincristine IV continuously on days 1-3 Courses repeat every 21 days During courses 3 and 5 patients receive etoposide VP-16 IV over 2 hours on days 1-3 and cisplatin IV over 1 hour on days 1-4 Courses repeat every 35 days Before proceeding to myeloablative therapytransplantation patients in stratum 2 must have received a minimum of 2 courses of chemotherapy if they achieved a complete response CR or very good partial response VGPR or patients must have received a minimum of 3 courses of chemotherapy if they achieved less than a CR or VGPR
Patients undergo tumor resection either at diagnosis or after completion of a minimum of 3 courses of chemotherapy approximately day 63
Treatment with monoclonal antibody 3F8 MOAB 3F8 starts after completion of course 3 of intensive induction chemotherapy preferably after surgical resection or debulking of the primary tumor Patients receive MOAB 3F8 IV over 90 minutes on days 1-5 of courses 3-5 and on days 1-5 immediately prior to transplantation
Harvest Autologous or syngeneic bone marrow or peripheral blood stem cells PBSC are harvested Patients undergoing PBSC collection receive filgrastim G-CSF beginning 2-3 days prior to collection and continuing through the end of collection For patients without bone marrow involvement at diagnosis autologous bone marrow or PBSC are harvested after completion of 1-2 courses of induction therapy For patients with bone marrow involvement at diagnosis bone marrow or PBSC are harvested after completion of 4 courses of induction therapy surgery and completion of 1 course of MOAB 3F8 if bone marrow is in remission If a patients bone marrowPBSC cannot be collected or harvested after completion of induction therapy because of hypoplasia or persistent tumor bone marrowPBSC collected or harvested before starting protocol or syngeneic bone marrowPBSC may be used If neither of these options is available patients who do not clear marrow by course 5 have the option of proceeding directly to the posttransplantation therapy phase below while delaying transplantation until bone marrow is clear
Myeloablative therapytransplantation Patients receive thiotepa IV over 3 hours on days -8 to -6 topotecan IV over 30 minutes on days -8 to -4 and carboplatin IV over 4 hours on days -5 to -3 Patients undergo autologous or syngeneic bone marrow transplantation BMT or PBSC transplantation PBSCT on day 0
Posttransplantation therapy Beginning 33 days after BMTPBSCT patients receive sargramostim GM-CSF subcutaneously on days 1-15 and MOAB 3F8 IV within 90 minutes beginning approximately 1 hour after initiation of GM-CSF infusion on days 6-15 Treatment repeats every 28 days for 2 courses
Beginning 47 days after BMTPBSCT on day 14 of course 1 of MOAB 3F8 and GM-CSF patients receive localized external beam radiotherapy twice daily for 7 consecutive weekdays
Beginning 82 days after BMTPBSCT patients receive alternating courses of oral VP-16 and MOAB 3F8 for a total of 8 courses total of 4 courses of each drug Patients receive oral VP-16 3 times daily on days 1-21 with courses repeating every 28 days Patients receive MOAB 3F8 IV within 90 minutes on days 1-5 with courses repeating every 35 days
Beginning 222 days after BMTPBSCT 2-3 weeks after completion of course 4 of oral VP-16 patients receive oral isotretinoin twice daily on days 1-14 Treatment repeats every 28 days for 6 courses
Beginning on day 243 after BMTPBSCT patients receive MOAB 3F8 IV within 90 minutes on days 1-5 Treatment repeats every 28 days for 6 courses
Treatment continues in the absence of disease progression or unacceptable toxicity
Patients are followed every 6 months for 2 years and then annually thereafter
PROJECTED ACCRUAL A maximum of 49 patients 34 for stratum 1 and 15 for stratum 2 will be accrued for this study within 3 years
Determine whether treatment with multimodality therapy comprising dose-intensive induction chemotherapy monoclonal antibody 3F8 surgery myeloablative chemotherapy autologous or syngeneic bone marrow or peripheral blood stem cell transplantation radiotherapy and isotretinoin improves the cure rate in patients with advanced neuroblastoma
Determine whether the 2-year progression-free survival PFS rate improves to 70 in patients with newly diagnosed advanced neuroblastoma treated with this regimen
Determine whether the 2-year PFS rate improves to 40 in patients with previously treated advanced neuroblastoma treated with this regimen
Determine the biologic and clinical prognostic factors of neuroblastoma that may guide future research of treatment approaches for this malignancy
OUTLINE Patients are stratified according to the following
Stratum 1 Patients with previously untreated stage IV disease who are over age 1 at diagnosis with or without N-myc amplification
Stratum 2 Patients with previously treated stage IV disease who are over age 1 at diagnosis or patients with previously treated high-risk disease eg N-myc amplified stage III or IV disease under age 1 at diagnosis and with or without prior treatment
Intensive induction therapy courses 1-5 During courses 1 2 and 4 patients receive cyclophosphamide IV over 6 hours on days 1 and 2 and doxorubicin and vincristine IV continuously on days 1-3 Courses repeat every 21 days During courses 3 and 5 patients receive etoposide VP-16 IV over 2 hours on days 1-3 and cisplatin IV over 1 hour on days 1-4 Courses repeat every 35 days Before proceeding to myeloablative therapytransplantation patients in stratum 2 must have received a minimum of 2 courses of chemotherapy if they achieved a complete response CR or very good partial response VGPR or patients must have received a minimum of 3 courses of chemotherapy if they achieved less than a CR or VGPR
Patients undergo tumor resection either at diagnosis or after completion of a minimum of 3 courses of chemotherapy approximately day 63
Treatment with monoclonal antibody 3F8 MOAB 3F8 starts after completion of course 3 of intensive induction chemotherapy preferably after surgical resection or debulking of the primary tumor Patients receive MOAB 3F8 IV over 90 minutes on days 1-5 of courses 3-5 and on days 1-5 immediately prior to transplantation
Harvest Autologous or syngeneic bone marrow or peripheral blood stem cells PBSC are harvested Patients undergoing PBSC collection receive filgrastim G-CSF beginning 2-3 days prior to collection and continuing through the end of collection For patients without bone marrow involvement at diagnosis autologous bone marrow or PBSC are harvested after completion of 1-2 courses of induction therapy For patients with bone marrow involvement at diagnosis bone marrow or PBSC are harvested after completion of 4 courses of induction therapy surgery and completion of 1 course of MOAB 3F8 if bone marrow is in remission If a patients bone marrowPBSC cannot be collected or harvested after completion of induction therapy because of hypoplasia or persistent tumor bone marrowPBSC collected or harvested before starting protocol or syngeneic bone marrowPBSC may be used If neither of these options is available patients who do not clear marrow by course 5 have the option of proceeding directly to the posttransplantation therapy phase below while delaying transplantation until bone marrow is clear
Myeloablative therapytransplantation Patients receive thiotepa IV over 3 hours on days -8 to -6 topotecan IV over 30 minutes on days -8 to -4 and carboplatin IV over 4 hours on days -5 to -3 Patients undergo autologous or syngeneic bone marrow transplantation BMT or PBSC transplantation PBSCT on day 0
Posttransplantation therapy Beginning 33 days after BMTPBSCT patients receive sargramostim GM-CSF subcutaneously on days 1-15 and MOAB 3F8 IV within 90 minutes beginning approximately 1 hour after initiation of GM-CSF infusion on days 6-15 Treatment repeats every 28 days for 2 courses
Beginning 47 days after BMTPBSCT on day 14 of course 1 of MOAB 3F8 and GM-CSF patients receive localized external beam radiotherapy twice daily for 7 consecutive weekdays
Beginning 82 days after BMTPBSCT patients receive alternating courses of oral VP-16 and MOAB 3F8 for a total of 8 courses total of 4 courses of each drug Patients receive oral VP-16 3 times daily on days 1-21 with courses repeating every 28 days Patients receive MOAB 3F8 IV within 90 minutes on days 1-5 with courses repeating every 35 days
Beginning 222 days after BMTPBSCT 2-3 weeks after completion of course 4 of oral VP-16 patients receive oral isotretinoin twice daily on days 1-14 Treatment repeats every 28 days for 6 courses
Beginning on day 243 after BMTPBSCT patients receive MOAB 3F8 IV within 90 minutes on days 1-5 Treatment repeats every 28 days for 6 courses
Treatment continues in the absence of disease progression or unacceptable toxicity
Patients are followed every 6 months for 2 years and then annually thereafter
PROJECTED ACCRUAL A maximum of 49 patients 34 for stratum 1 and 15 for stratum 2 will be accrued for this study within 3 years
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 |
|---|---|---|---|
| NCI-G02-2083 | US NIH GrantContract | None | httpsreporternihgovquickSearchP30CA008748 |
| P30CA008748 | NIH | None | None |
| MSKCC-00065 | None | None | None |