Ignite Creation Date:
2024-05-05 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00135135
Status:
COMPLETED
Last Update Posted:
2008-06-03
First Post:
2005-08-24
Brief Title:
Therapy for Children With Neuroblastoma
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Neuroblastoma Protocol 2005 Therapy for Children With Advanced Stage High-Risk Neuroblastoma
Status:
COMPLETED
Status Verified Date:
2008-06
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 window study of the combination of ZD1839 gefitinib and irinotecan in children with high-risk neuroblastoma followed by standard induction chemotherapy intensification with autologous stem cell transplantation and an oral maintenance phase with 13-cis-retinoic acid and topotecan We hypothesize that the ZD1839 gefitinib and irinotecan window will be efficacious
Detailed Description:
The study will have five parts or phases In the first part the combination of irinotecan and gefitinib will be studied After that patients who have responded well will have surgery to remove the tumor This will be followed by a third part which includes about nine months of treatment with cisplatin adriamycin etoposide cyclophosphamide and topotecan The fourth part will be intensification with melphalan etoposide and carboplatin and blood stem cell rescue During this part radiation will also be given to the sites of the disease Finally monthly treatments with oral retinoic acid alternating with oral topotecan will be continued for a total of 16 months of maintenance It is anticipated that it will take about 2 years to complete this entire treatment plan
This study has multiple therapeutic pharmacologic biologic and diagnostic imaging objectives
To estimate whether oral gefitinib with two courses of intravenous irinotecan will decrease the incidence of feverneutropenia duration of hospitalization duration of intravenous antibiotics and numbers of platelet and RBC transfusions during the first six weeks of treatment compared to the topotecan window in NB97
To estimate local control of primary site disease to this treatment plan
To estimate the overall survival and progression-free survival in patients treated with this approach
To estimate the feasibility of resecting the primary tumor after two courses of irinotecan and gefitinib
To evaluate the disposition of irinotecan and gefitinib in previously untreated patients with neuroblastoma
To evaluate the disposition of intravenous and oral topotecan in previously untreated patients with neuroblastoma
To evaluate the pharmacogenetic determinants of gefitinib and irinotecan pharmacokinetics and pharmacodynamics eg CYP3A45 UGT1A1 and ABCG2 BCRP polymorphisms
To evaluate the pharmacogenetic determinants of topotecan pharmacokinetics and pharmacodynamics eg CYP3A45 and ABC transporter polymorphisms
To evaluate in tumor samples the molecular and cellular expression of EGFR MRP4 and ABCG2 BCRP utilizing appropriate laboratory techniques
To describe the relative frequency of positive bone marrow by sensitive MRD methods at diagnosis after window therapy at the time of stem cell harvest and at several time points following the completion of intensification These results will be compared with timing and pattern of disease recurrence
To describe what percentage of primary or metastatic neuroblastomas have amplified ICAM-2 and chromosome 17
To generate preliminary data regarding the potential use of ICAM-2 copy number as a prognostic indicator in neuroblastoma
To determine the levels of the angiogenic factors VEGF and bFGF in the peripheral circulation of patients at diagnosis after window therapy at the time of stem cell harvest and at several time points following the completion of intensification These results will be compared with the degree of tumor response and the timing of disease recurrence
To procure tumor samples for construction of tissue microarray blocks that will be utilized in further biologic characterization of these tumors
To prospectively evaluate FDG PET imaging as a marker of disease at diagnosis pre and post window therapy prior to intensification and at the completion of therapy
To generate preliminary data on the use of contrast enhanced ultrasound and magnetic resonance imaging to evaluate changes in tumor vascularity at various timepoints in therapy
Details of Treatment Interventions
Window Phase Irinotecan 15mgm2 daily x 5 days for two weeks with daily oral gefitinib 1125 mgm2 daily x 12 days followed by 9 day rest then same course repeated Subjects that respond to window therapy receive the same course again instead of topotecan for Block 2 course 6 week 21 of induction
Induction Therapy following window
Cyclophosphamide 15 gmm2 daily x 2 IV day 1 2 Adriamycin 50 mgm2 IV day 1 only MESNA 375 mgm2 IV immediately following cyclophosphamide and at 3 and 6 hours post-infusion
Etoposide 30 mgm2 over 30 minutes followed by etoposide 250 mgm2day x 3 days IV by continuous infusion days 2-5 given during induction therapy courses 1 4 and 7
Cisplatin 40 mgm2day x 5 IV over 1 hour days 1-5 Etoposide 200 mgm2day x 3 IV over 1 hour days 2 3 4 given during induction courses 2 5 and 8
IV topotecan adjusted to AUC 100 20nghrml daily x 5 days for two weeks during courses 3 6 for patients that do not respond to window and 9 of induction
Intensification
Melphalan Etopophos and carboplatinDay -8 -7 -6 -5 Melphalan 45 mgm2 IV Day -4 Etopophos 40 mgkgday IV Day -4 -3 -2 Carboplatin AUC target 41 Day 0- infusion of peripheral blood stem cells previously harvested by pheresis
Maintenance
13 cis-retinoic acid and oral topotecan courses13-cis-retinoic acid 160 mgm2day divided into two equal doses given orally BID x 14 days followed by a 14 day rest This will be repeated x one Subjects less or equal to 12 kg will be given 533 mgkgday divided BID These courses are alternated with 2 months of oral topotecan once daily for 5 days for 2 consecutive weeks at 18 mgm2day or 006 mgkgday for patients less than 12 months old total of 10 doses for a total of 16 courses four two-month courses of each
Radiation therapy Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiation External beam radiotherapy will be delivered to the primary site and select metastatic sites Radiotherapy is planned to be initiated four weeks following stem cell reinfusion
Surgery After recovery from induction and re-evaluation of tumor status subjects undergo surgery for resection of the primary tumor mass and careful lymph node staging if surgery was not possible after the irinotecan and ZD1839 window
Peripheral blood stem cell collection and infusion After course 3 subjects undergo peripheral blood stem cell PBSC harvest If this is unsuccessful harvesting will be done with subsequent chemotherapy courses Subjects are mobilized with filgrastim 10mcgkgday PBSC harvesting will be performed by leukapheresis if possible bone marrow harvest if not Stem cells are stored and re-infused after intensification chemotherapy
This study has multiple therapeutic pharmacologic biologic and diagnostic imaging objectives
To estimate whether oral gefitinib with two courses of intravenous irinotecan will decrease the incidence of feverneutropenia duration of hospitalization duration of intravenous antibiotics and numbers of platelet and RBC transfusions during the first six weeks of treatment compared to the topotecan window in NB97
To estimate local control of primary site disease to this treatment plan
To estimate the overall survival and progression-free survival in patients treated with this approach
To estimate the feasibility of resecting the primary tumor after two courses of irinotecan and gefitinib
To evaluate the disposition of irinotecan and gefitinib in previously untreated patients with neuroblastoma
To evaluate the disposition of intravenous and oral topotecan in previously untreated patients with neuroblastoma
To evaluate the pharmacogenetic determinants of gefitinib and irinotecan pharmacokinetics and pharmacodynamics eg CYP3A45 UGT1A1 and ABCG2 BCRP polymorphisms
To evaluate the pharmacogenetic determinants of topotecan pharmacokinetics and pharmacodynamics eg CYP3A45 and ABC transporter polymorphisms
To evaluate in tumor samples the molecular and cellular expression of EGFR MRP4 and ABCG2 BCRP utilizing appropriate laboratory techniques
To describe the relative frequency of positive bone marrow by sensitive MRD methods at diagnosis after window therapy at the time of stem cell harvest and at several time points following the completion of intensification These results will be compared with timing and pattern of disease recurrence
To describe what percentage of primary or metastatic neuroblastomas have amplified ICAM-2 and chromosome 17
To generate preliminary data regarding the potential use of ICAM-2 copy number as a prognostic indicator in neuroblastoma
To determine the levels of the angiogenic factors VEGF and bFGF in the peripheral circulation of patients at diagnosis after window therapy at the time of stem cell harvest and at several time points following the completion of intensification These results will be compared with the degree of tumor response and the timing of disease recurrence
To procure tumor samples for construction of tissue microarray blocks that will be utilized in further biologic characterization of these tumors
To prospectively evaluate FDG PET imaging as a marker of disease at diagnosis pre and post window therapy prior to intensification and at the completion of therapy
To generate preliminary data on the use of contrast enhanced ultrasound and magnetic resonance imaging to evaluate changes in tumor vascularity at various timepoints in therapy
Details of Treatment Interventions
Window Phase Irinotecan 15mgm2 daily x 5 days for two weeks with daily oral gefitinib 1125 mgm2 daily x 12 days followed by 9 day rest then same course repeated Subjects that respond to window therapy receive the same course again instead of topotecan for Block 2 course 6 week 21 of induction
Induction Therapy following window
Cyclophosphamide 15 gmm2 daily x 2 IV day 1 2 Adriamycin 50 mgm2 IV day 1 only MESNA 375 mgm2 IV immediately following cyclophosphamide and at 3 and 6 hours post-infusion
Etoposide 30 mgm2 over 30 minutes followed by etoposide 250 mgm2day x 3 days IV by continuous infusion days 2-5 given during induction therapy courses 1 4 and 7
Cisplatin 40 mgm2day x 5 IV over 1 hour days 1-5 Etoposide 200 mgm2day x 3 IV over 1 hour days 2 3 4 given during induction courses 2 5 and 8
IV topotecan adjusted to AUC 100 20nghrml daily x 5 days for two weeks during courses 3 6 for patients that do not respond to window and 9 of induction
Intensification
Melphalan Etopophos and carboplatinDay -8 -7 -6 -5 Melphalan 45 mgm2 IV Day -4 Etopophos 40 mgkgday IV Day -4 -3 -2 Carboplatin AUC target 41 Day 0- infusion of peripheral blood stem cells previously harvested by pheresis
Maintenance
13 cis-retinoic acid and oral topotecan courses13-cis-retinoic acid 160 mgm2day divided into two equal doses given orally BID x 14 days followed by a 14 day rest This will be repeated x one Subjects less or equal to 12 kg will be given 533 mgkgday divided BID These courses are alternated with 2 months of oral topotecan once daily for 5 days for 2 consecutive weeks at 18 mgm2day or 006 mgkgday for patients less than 12 months old total of 10 doses for a total of 16 courses four two-month courses of each
Radiation therapy Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiation External beam radiotherapy will be delivered to the primary site and select metastatic sites Radiotherapy is planned to be initiated four weeks following stem cell reinfusion
Surgery After recovery from induction and re-evaluation of tumor status subjects undergo surgery for resection of the primary tumor mass and careful lymph node staging if surgery was not possible after the irinotecan and ZD1839 window
Peripheral blood stem cell collection and infusion After course 3 subjects undergo peripheral blood stem cell PBSC harvest If this is unsuccessful harvesting will be done with subsequent chemotherapy courses Subjects are mobilized with filgrastim 10mcgkgday PBSC harvesting will be performed by leukapheresis if possible bone marrow harvest if not Stem cells are stored and re-infused after intensification chemotherapy
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| AstraZeneca IRUSIERS0389 | None | None | None |