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

Neuroblastoma Clinical Trial

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)]

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00392340
• Other study ID #: CDR0000508641
• Secondary ID: CCLG-NB-2006-05E
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 25, 2006
• Last updated: September 16, 2013
• Start date: March 2008

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 63
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 20 Years

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• filgrastim

Drug:
• doxorubicin hydrochloride

• topotecan hydrochloride

• vincristine sulfate

Locations

Country	Name	City	State
United Kingdom	Institute of Child Health at University of Bristol	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (complete or partial) > 50% after 2 courses of topotecan hydrochloride, vincristine, and doxorubicin hydrochloride			No
Secondary	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			No
Secondary	Toxicity and incidence of adverse events			Yes