Clinical trial NCT00276679: Temozolomide in Treating Young Patients With High-Risk Relapsed or Refractory Neuroblastoma
Official title: Phase II Study of Temozolomide (Temodal) in Children Over 1 Year of Age With Relapsed or Refractory High Risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: recurrent neuroblastoma
disseminated neuroblastoma
localized unresectable neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-01-13
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Centre Hospitalier Regional de Purpan
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
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 at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: Royal London Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
state: England
city: Manchester
country: United Kingdom
facility: Central Manchester and Manchester Children's University Hospitals NHS Trust
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
state: Scotland
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
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: Centre Hospitalier Regional de Purpan
name: Herve Rubie, MD
role: STUDY_CHAIR
affiliation: University of Newcastle Upon-Tyne
name: Andrew David J. Pearson, MD, FRCP, DCh
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Julia Chisholm, MD
References:
citation: Rubie H, Chisholm J, Defachelles AS, Morland B, Munzer C, Valteau-Couanet D, Mosseri V, Bergeron C, Weston C, Coze C, Auvrignon A, Djafari L, Hobson R, Baunin C, Dickinson F, Brisse H, McHugh K, Biassoni L, Giammarile F, Vassal G; Societe Francaisedes Cancers de l'Enfant; United Kingdom Children Cancer Study Group-New Agents Group Study. Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Societe Francaise des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. J Clin Oncol. 2006 Nov 20;24(33):5259-64. doi: 10.1200/JCO.2006.06.1572.