Temozolomide in Treating Young Patients With High-Risk Relapsed or Refractory Neuroblastoma

Children's Cancer and Leukaemia Group

Status and phase: Completed; Phase 2

Conditions: Neuroblastoma

Treatments: Drug: temozolomide

Study type: Interventional

Funder types: Other

Identifiers

NCT00276679

CCLG-NAG-2003-02

CDR0000454577

EU-20591

CCLG-SFOP-NAG-2003-02

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with high-risk relapsed or refractory neuroblastoma.

Full description

OBJECTIVES:

Primary

• Determine the anti-tumor activity of temozolomide in young patients with high-risk relapsed or refractory neuroblastoma.

Secondary

• Determine the duration of response in patients treated with this drug.
• Determine tolerability of this drug in these patients
• Determine the tumor expression of the cellular repair mechanisms which repair DNA damage (O6-methylguanine-DNA methyltransferase [MGMT] and mismatch repair [MMR] systems) in patients treated with this drug.
• Correlate MGMT and MMR expression with outcomes in patients treated with this drug.
• Determine if MGMT and MMR expression/activity changes in the tumor during initial presentation, treatment, and relapse/progression in patients treated with this drug.
• Determine the activity of MGMT in bone marrow taken at relapse, in terms of hematological toxicity, in patients treated with this drug.

OUTLINE: This is a multicenter, open label, nonrandomized study.

Patients receive oral temozolomide once daily for 5 days. Treatment repeats every 28 days for 2 courses. Patients achieving stable or responding disease after completion of the 2 courses may receive up to 10 additional courses of treatment in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Sex: All

Ages: 1 to 16 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven neuroblastoma

  • High-risk relapsed or refractory disease, defined as 1 of the following:

    • Metastatic disease
    • Localized MYC-N amplified disease
    • Localized non MYC-N amplified disease at second relapse

• Measurable primary or metastatic disease by cross-sectional imaging or MIBG scan

PATIENT CHARACTERISTICS:

• Lansky performance status 40-100%
• Life expectancy > 2 months
• Not pregnant or nursing
• Fertile patients must use effective contraception during the course of this study and for 6 months after study completion
• Organ toxicity < grade 2
• Platelets ≥ 100,000/mm^3 (50,000/mm^3 after stem cell transplant or in case of marrow involvement)
• Neutrophil count ≥ 500/mm^3
• Bilirubin < 1.5 times normal
• AST and ALT ≤ 2.5 times normal
• No known HIV positivity

PRIOR CONCURRENT THERAPY:

• More than 21 days since prior chemotherapy treatment (isotretinoin is counted as chemotherapy for this purpose)
• More than 30 days since prior radiotherapy except local palliative treatment for pain control
• No more than 2 prior treatments for neuroblastoma
• No other concurrent investigative treatment for neuroblastoma