Therapy for Children With Advanced Stage High Risk Neuroblastoma
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|ClinicalTrials.gov Identifier: NCT00186849|
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : May 20, 2009
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Drug: Topotecan, Cyclophosphamide, Cisplatin, Doxorubicin, Etoposide, Ifosfamide, Carboplatin Procedure: Peripheral Blood Stem Cell Transplant||Phase 2|
Hide 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 3.0 mg/m2 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.
Cyclophosphamide, MESNA, Adriamycin, Cisplatin, Carboplatin, and Etoposide description, Induction Phase (after completion of window) consists of 4 cycles of therapy:
Cycle 1:Cyclophosphamide 1 gm/m2 daily x 2 I.V. day 1 and 2 Adriamycin 35 mg/m2 I.V. day 1 only, MESNA: 250 mg/m2 I.V. immediately following cyclophosphamide infusion and at 3 and 6 hours post-infusion, and Etoposide: 30 mg/m2 over 30 minutes, followed by 250 mg/m2/day x 3 days I.V. by continuous infusion (days 2-5) Cycles 2 and 4- Cisplatin 40 mg/m2/day x 5 I.V. over 1 hour (days 1-5) Etoposide 200 mg/m2/day x 3 I.V. over 1 hour (days 2,3,4) Cycle 3: Carboplatin: dose adapted from GFR on day 1. Dose in mg/m2 = 8 x [(0.93 GFR) + 15] Ifosfamide: 2 gm/m2 I.V. over 1 hour daily x 3 (days 2, 3, 4) MESNA: 500 mg/m2 I.V. immediately after ifosfamide and 3 and 6 hours later Etoposide: 100 mg/m2 IV daily x 3 over 1 hour (days 2, 3, 4).
Topotecan, Cyclophosphamide, and MESNA- Intensification Therapy:
Topotecan - targeted dose - daily x 5 days for two weeks. Cyclophosphamide 750 mg/m2 IV over 1 hour on days 8 through 12. MESNA 175 mg/m2 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 mg/m2/day IV, over one hour q.o.d. x 3 Etoposide 500 mg/m2/day IV, over 6 hours q.o.d. x 3. Infusion of previously collected peripheral blood stem cells on day 8
Details for Intervention: Procedure/Surgery: 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Therapy for Children With Advanced Stage High Risk Neuroblastoma|
|Study Start Date :||October 1997|
|Actual Primary Completion Date :||April 2001|
|Actual Study Completion Date :||April 2001|
Drug: Topotecan, Cyclophosphamide, Cisplatin, Doxorubicin, Etoposide, Ifosfamide, Carboplatin
See Detailed Description section for details of treatment interventions.Procedure: Peripheral Blood Stem Cell Transplant
See Detailed Description section for details of treatment interventions.
- Response rate [ Time Frame: 5 years ]
- Feasibility/toxicity of an intensification phase of high-dose chemotherapy with topotecan and cyclophosphamide followed by autologous peripheral blood stem cell transplant [ Time Frame: 5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00186849
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||Wayne L. Furman, MD||St. Jude Children's Research Hospital|