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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neuroblastoma	Biological: filgrastim; Drug: doxorubicin hydrochloride; Drug: topotecan hydrochloride; Drug: vincristine sulfate	Phase 2

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	63 participants
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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)]
Study Start Date :	March 2008
Estimated Primary Completion Date :	January 2010

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Objective response rate (complete or partial) > 50% after 2 courses of topotecan hydrochloride, vincristine, and doxorubicin hydrochloride

Secondary Outcome Measures :

1. 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
2. Toxicity and incidence of adverse events

Eligibility Criteria

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Ages Eligible for Study:	1 Year to 20 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United Kingdom
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Great Ormond Street Hospital for Children
London, England, United Kingdom, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health at Royal Victoria Infirmary
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ

Sponsors and Collaborators

Children's Cancer and Leukaemia Group

Investigators

Study Chair:	Guy Makin, MD, PhD	Royal Manchester Children's Hospital

More Information

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ClinicalTrials.gov Identifier:	NCT00392340 History of Changes
Other Study ID Numbers:	CDR0000508641; CCLG-NB-2006-05; EUDRACT-2005-000915-80; EU-20641
First Posted:	October 26, 2006
Last Update Posted:	September 17, 2013
Last Verified:	June 2009

Keywords provided by National Cancer Institute (NCI):

recurrent neuroblastoma; disseminated neuroblastoma

Additional relevant MeSH terms:

Neuroblastoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Doxorubicin; Liposomal doxorubicin; Vincristine	Topotecan; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors