Clinical trial NCT00392340: Topotecan, Vincristine, and Doxorubicin in Treating Young Patients With Refractory Stage 4 Neuroblastoma
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: recurrent neuroblastoma
disseminated neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-10-26
Enrollment: 63
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Objective response rate (complete or partial) > 50% after 2 courses of topotecan hydrochloride, vincristine, and doxorubicin hydrochloride
Secondary outcomes:
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
measure: Toxicity and incidence of adverse events
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Institute of Child Health at University of Bristol
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
Study officials:
affiliation: Royal Manchester Children's Hospital
name: Guy Makin, MD, PhD
role: STUDY_CHAIR
References: