Topotecan, Vincristine, and Doxorubicin in Treating Young Patients With Refractory Stage 4 Neuroblastoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as topotecan, vincristine, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving topotecan together with vincristine and doxorubicin works in treating young patients with refractory stage 4 neuroblastoma.

Detailed Description
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OBJECTIVES: Primary Assess whether treatment with topotecan hydrochloride, vincristine, and doxorubicin hydrochloride can achieve a satisfactory response rate in pediatric patients with stage 4 neuroblastoma that failed to respond to rapid first-line treatment. Secondary Determine time to progression in these patients. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter, open-label study. Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5 and vincristine IV continuously and doxorubicin hydrochloride IV continuously over 48 hours on days 5 and 6. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 9 and continuing until blood counts recover. Treatment repeats every 21-28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve partial response (PR) after two courses of treatment receive an additional two courses. Patients who achieve complete response or very good PR are treated according to the standard therapy in protocol SIOP-EUROPE- HR-NBL-1. Patients who fail to achieve PR after 2 courses receive further treatment at the physician's discretion. Patients are followed periodically for at least 3 years. PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study.

Official Title
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An Open-Label, Multicentre, Phase II Study of TVD as Treatment for Children With Stage 4 Neuroblastoma Failing to Respond to First-Line Treatment According to HR-NBL-01/ E-SIOP [Topotecan-Vincristine-Doxorubicin in Children With Stage 4 Neuroblastoma Failing to Respond to COJEC (TVD)]

Conditions
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Neuroblastoma

Intervention / Treatment
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* Biological: filgrastim
* Drug: doxorubicin hydrochloride
* Drug: topotecan hydrochloride
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage 4 neuroblastoma Failed to achieve adequate metastatic partial response after first-line therapy while enrolled on protocol SIOP-EUROPE-HR-NBL-1 PATIENT CHARACTERISTICS: Neutrophil count > 1,000/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.36 mg/dL Bilirubin ≤ 2.92 mg/dL AST and ALT < 2.5 times upper limit of normal Glomerular filtration rate ≥ 60 mL/min Normal cardiac function on echocardiography No severe organ dysfunction No active hepatitis C or hepatitis B virus positivity No HIV infection PRIOR CONCURRENT THERAPY: No anti-tumor chemotherapy within the past 10 days No radiotherapy within the past 30 days No other investigational drugs within the past 30 days No prior doxorubicin hydrochloride

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: topotecan hydrochloride|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (complete or partial) > 50% after 2 courses of topotecan hydrochloride, vincristine, and doxorubicin hydrochloride |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at the time of local progression or relapse, progression of pre-existing metastases, metastatic relapse, second primary malignancy, or death from any cause |  |  | 
| Toxicity and incidence of adverse events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent neuroblastoma, disseminated neuroblastoma