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

September 16, 2013 updated by: Children's Cancer and Leukaemia Group

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)]

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 20 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Cancer and Leukaemia Group

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (ANTICIPATED)

January 1, 2010

Study Registration Dates

First Submitted

October 25, 2006

First Submitted That Met QC Criteria

October 25, 2006

First Posted (ESTIMATE)

October 26, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

September 17, 2013

Last Update Submitted That Met QC Criteria

September 16, 2013

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000508641
  • CCLG-NB-2006-05
  • EUDRACT-2005-000915-80
  • EU-20641

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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