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

Children's Cancer and Leukaemia Group

Status and phase: Unknown; Phase 2

Conditions: Neuroblastoma

Treatments: Drug: topotecan hydrochloride; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim

Study type: Interventional

Funder types: Other

Identifiers

NCT00392340

CDR0000508641

CCLG-NB-2006-05

EUDRACT-2005-000915-80

EU-20641

Details and patient eligibility

About

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.

Full 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.

Enrollment: 63 estimated patients

Sex: All

Ages: 1 to 20 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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