Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00186849
Status:
COMPLETED
Last Update Posted:
2009-05-20
First Post:
2005-09-12
Brief Title:
Therapy for Children With Advanced Stage High Risk Neuroblastoma
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Therapy for Children With Advanced Stage High Risk Neuroblastoma
Status:
COMPLETED
Status Verified Date:
2009-05
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:
This is a Phase II pilot study of chemotherapy and surgery for children with advanced stage high-risk neuroblastoma utilizing topotecan during an upfront window and other active agents during induction and intensification phases The primary purpose is to estimate the response rate to an upfront window of two cycles of intravenous topotecan We hypothesize that the topotecan window will be an effective therapy in terms of the response rate
Detailed Description:
In this prospective phase II trial topotecan is administered intravenously daily for 5 days for each of 2 consecutive weeks for two cycles in an upfront treatment window Patients subsequently will receive standard treatment during induction and intensification phases
The objectives of this trial are
To estimate the response rate to an upfront window of two cycles of IV topotecan when given in doses adjusted to attain a targeted systemic exposure in children with advanced stage neuroblastoma
To determine the feasibility and toxicity of an intensification phase of high-dose chemotherapy with topotecan and cyclophosphamide followed by autologous peripheral blood stem cell transplant
To estimate the 3-year overall survival and progression-free survival in patients treated with this approach
To characterize the phenotype of neuroblastoma tumor cells
To evaluate the disposition of topotecan in previously untreated patients with neuroblastoma
Details for chemotherapy intervention
Window Phase Topotecan description window therapy-Topotecan given intravenously daily as a 30 minute infusion for five consecutive days off two days and then five consecutive days The dose for day 1 and 2 was 30 mgm2 and subsequent doses were adjusted to attain a target systemic exposure A second course of Topotecan was given approximately 16 days from the end of the first cycle with the initial dose for the second course of Topotecan based on the dose required in the preceding course to attain the target AUC
Induction Phase
Cyclophosphamide MESNA Adriamycin Cisplatin Carboplatin and Etoposide description Induction Phase after completion of window consists of 4 cycles of therapy
Cycle 1Cyclophosphamide 1 gmm2 daily x 2 IV day 1 and 2 Adriamycin 35 mgm2 IV day 1 only MESNA 250 mgm2 IV immediately following cyclophosphamide infusion and at 3 and 6 hours post-infusion and Etoposide 30 mgm2 over 30 minutes followed by 250 mgm2day x 3 days IV by continuous infusion days 2-5 Cycles 2 and 4- Cisplatin 40 mgm2day x 5 IV over 1 hour days 1-5 Etoposide 200 mgm2day x 3 IV over 1 hour days 234 Cycle 3 Carboplatin dose adapted from GFR on day 1 Dose in mgm2 8 x 093 GFR 15 Ifosfamide 2 gmm2 IV over 1 hour daily x 3 days 2 3 4 MESNA 500 mgm2 IV immediately after ifosfamide and 3 and 6 hours later Etoposide 100 mgm2 IV daily x 3 over 1 hour days 2 3 4
Intensification Phase
Topotecan Cyclophosphamide and MESNA- Intensification Therapy
Topotecan - targeted dose - daily x 5 days for two weeks Cyclophosphamide 750 mgm2 IV over 1 hour on days 8 through 12 MESNA 175 mgm2 IV immediately after cyclophosphamide and 3 and 6 hours later Infusion of previously collected peripheral blood stem cells on day 14
Subjects that do not respond to the Topotecan window will not receive topotecan during intensification but instead will receive the following intensification therapy
Carboplatin 700 mgm2day IV over one hour qod x 3 Etoposide 500 mgm2day IV over 6 hours qod x 3 Infusion of previously collected peripheral blood stem cells on day 8
Details for Intervention ProcedureSurgery Surgery Surgical resection will be performed after the window therapy in feasible subjects If surgery was not possible after the Topotecan window resection of the primary tumor mass and careful lymph node staging was done after recovery from induction and re-evaluation of tumor status
The objectives of this trial are
To estimate the response rate to an upfront window of two cycles of IV topotecan when given in doses adjusted to attain a targeted systemic exposure in children with advanced stage neuroblastoma
To determine the feasibility and toxicity of an intensification phase of high-dose chemotherapy with topotecan and cyclophosphamide followed by autologous peripheral blood stem cell transplant
To estimate the 3-year overall survival and progression-free survival in patients treated with this approach
To characterize the phenotype of neuroblastoma tumor cells
To evaluate the disposition of topotecan in previously untreated patients with neuroblastoma
Details for chemotherapy intervention
Window Phase Topotecan description window therapy-Topotecan given intravenously daily as a 30 minute infusion for five consecutive days off two days and then five consecutive days The dose for day 1 and 2 was 30 mgm2 and subsequent doses were adjusted to attain a target systemic exposure A second course of Topotecan was given approximately 16 days from the end of the first cycle with the initial dose for the second course of Topotecan based on the dose required in the preceding course to attain the target AUC
Induction Phase
Cyclophosphamide MESNA Adriamycin Cisplatin Carboplatin and Etoposide description Induction Phase after completion of window consists of 4 cycles of therapy
Cycle 1Cyclophosphamide 1 gmm2 daily x 2 IV day 1 and 2 Adriamycin 35 mgm2 IV day 1 only MESNA 250 mgm2 IV immediately following cyclophosphamide infusion and at 3 and 6 hours post-infusion and Etoposide 30 mgm2 over 30 minutes followed by 250 mgm2day x 3 days IV by continuous infusion days 2-5 Cycles 2 and 4- Cisplatin 40 mgm2day x 5 IV over 1 hour days 1-5 Etoposide 200 mgm2day x 3 IV over 1 hour days 234 Cycle 3 Carboplatin dose adapted from GFR on day 1 Dose in mgm2 8 x 093 GFR 15 Ifosfamide 2 gmm2 IV over 1 hour daily x 3 days 2 3 4 MESNA 500 mgm2 IV immediately after ifosfamide and 3 and 6 hours later Etoposide 100 mgm2 IV daily x 3 over 1 hour days 2 3 4
Intensification Phase
Topotecan Cyclophosphamide and MESNA- Intensification Therapy
Topotecan - targeted dose - daily x 5 days for two weeks Cyclophosphamide 750 mgm2 IV over 1 hour on days 8 through 12 MESNA 175 mgm2 IV immediately after cyclophosphamide and 3 and 6 hours later Infusion of previously collected peripheral blood stem cells on day 14
Subjects that do not respond to the Topotecan window will not receive topotecan during intensification but instead will receive the following intensification therapy
Carboplatin 700 mgm2day IV over one hour qod x 3 Etoposide 500 mgm2day IV over 6 hours qod x 3 Infusion of previously collected peripheral blood stem cells on day 8
Details for Intervention ProcedureSurgery Surgery Surgical resection will be performed after the window therapy in feasible subjects If surgery was not possible after the Topotecan window resection of the primary tumor mass and careful lymph node staging was done after recovery from induction and re-evaluation of tumor status
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None