## Protocol Section
### Identification Module
**NCT ID:** NCT00276679

**Brief Title:** 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

#### Organization Study ID Info
**ID:** CDR0000454577
#### Organization
**Class:** NIH
**Full Name:** National Cancer Institute (NCI)
#### Secondary ID Infos
**ID:** CCLG-NAG-2003-02
**ID:** EU-20591
**ID:** CCLG-SFOP-NAG-2003-02
### Status Module
#### Completion Date
**Date:** 2006-11

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2013-09-17

**Type:** ESTIMATED

**Last Update Submit Date:** 2013-09-16

**Overall Status:** COMPLETED

#### Start Date
**Date:** 2003-04

**Status Verified Date:** 2006-01

#### Study First Post Date
**Date:** 2006-01-13
**Type:** ESTIMATED
**Study First Submit Date:** 2006-01-12
**Study First Submit QC Date:** 2006-01-12
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Children's Cancer and Leukaemia Group

### Description Module

**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.

### Conditions Module

**Conditions:**

- Neuroblastoma

**Keywords:**

- recurrent neuroblastoma

- disseminated neuroblastoma

- localized unresectable neuroblastoma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

### Interventions

#### Intervention 1

**Name:** temozolomide

**Type:** DRUG

### Eligibility Module

**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

**Maximum Age:** 16 Years

**Minimum Age:** 1 Year

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Toulouse

**Country:** France

**Facility:** Centre Hospitalier Regional de Purpan

**Zip:** 31026

**Location 2:**

**City:** Dublin

**Country:** Ireland

**Facility:** Our Lady's Hospital for Sick Children

**Zip:** 12

**Location 3:**

**City:** Birmingham

**Country:** United Kingdom

**Facility:** Birmingham Children's Hospital

**State:** England

**Zip:** B4 6NH

**Location 4:**

**City:** Bristol

**Country:** United Kingdom

**Facility:** Institute of Child Health at University of Bristol

**State:** England

**Zip:** BS2 8AE

**Location 5:**

**City:** Cambridge

**Country:** United Kingdom

**Facility:** Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

**State:** England

**Zip:** CB2 2QQ

**Location 6:**

**City:** Leeds

**Country:** United Kingdom

**Facility:** Leeds Cancer Centre at St. James's University Hospital

**State:** England

**Zip:** LS9 7TF

**Location 7:**

**City:** Leicester

**Country:** United Kingdom

**Facility:** Leicester Royal Infirmary

**State:** England

**Zip:** LE1 5WW

**Location 8:**

**City:** Liverpool

**Country:** United Kingdom

**Facility:** Royal Liverpool Children's Hospital, Alder Hey

**State:** England

**Zip:** L12 2AP

**Location 9:**

**City:** London

**Country:** United Kingdom

**Facility:** Royal London Hospital

**State:** England

**Zip:** E1 1BB

**Location 10:**

**City:** London

**Country:** United Kingdom

**Facility:** Great Ormond Street Hospital for Children NHS Trust

**State:** England

**Zip:** WC1N 3JH

**Location 11:**

**City:** Manchester

**Country:** United Kingdom

**Facility:** Central Manchester and Manchester Children's University Hospitals NHS Trust

**State:** England

**Zip:** M27 4HA

**Location 12:**

**City:** Newcastle-Upon-Tyne

**Country:** United Kingdom

**Facility:** Sir James Spence Institute of Child Health

**State:** England

**Zip:** NE1 4LP

**Location 13:**

**City:** Nottingham

**Country:** United Kingdom

**Facility:** Queen's Medical Centre

**State:** England

**Zip:** NG7 2UH

**Location 14:**

**City:** Oxford

**Country:** United Kingdom

**Facility:** Oxford Radcliffe Hospital

**State:** England

**Zip:** 0X3 9DU

**Location 15:**

**City:** Sheffield

**Country:** United Kingdom

**Facility:** Children's Hospital - Sheffield

**State:** England

**Zip:** S10 2TH

**Location 16:**

**City:** Southampton

**Country:** United Kingdom

**Facility:** Southampton General Hospital

**State:** England

**Zip:** SO16 6YD

**Location 17:**

**City:** Sutton

**Country:** United Kingdom

**Facility:** Royal Marsden NHS Foundation Trust - Surrey

**State:** England

**Zip:** SM2 5PT

**Location 18:**

**City:** Belfast

**Country:** United Kingdom

**Facility:** Royal Belfast Hospital for Sick Children

**State:** Northern Ireland

**Zip:** BT12 6BE

**Location 19:**

**City:** Aberdeen

**Country:** United Kingdom

**Facility:** Royal Aberdeen Children's Hospital

**State:** Scotland

**Zip:** AB25 2ZG

**Location 20:**

**City:** Edinburgh

**Country:** United Kingdom

**Facility:** Royal Hospital for Sick Children

**State:** Scotland

**Zip:** EH9 1LF

**Location 21:**

**City:** Glasgow

**Country:** United Kingdom

**Facility:** Royal Hospital for Sick Children

**State:** Scotland

**Zip:** G3 8SJ

**Location 22:**

**City:** Cardiff

**Country:** United Kingdom

**Facility:** Childrens Hospital for Wales

**State:** Wales

**Zip:** CF14 4XW

#### Overall Officials

**Official 1:**

**Affiliation:** Centre Hospitalier Regional de Purpan

**Name:** Herve Rubie, MD

**Role:** STUDY_CHAIR

**Official 2:**

**Affiliation:** University of Newcastle Upon-Tyne

**Name:** Andrew David J. Pearson, MD, FRCP, DCh

**Official 3:**

**Affiliation:** Great Ormond Street Hospital for Children NHS Foundation Trust

**Name:** Julia Chisholm, MD

### References Module

#### 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.

**PMID:** 17114659

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018241

- Term: Neuroectodermal Tumors, Primitive, Peripheral

- ID: D000018242

- Term: Neuroectodermal Tumors, Primitive

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M12391

- Name: Neuroblastoma

- Relevance: HIGH

- As Found: Neuroblastoma

- ID: M20387

- Name: Neuroectodermal Tumors, Primitive, Peripheral

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T4085

- Name: Neuroblastoma

- Relevance: HIGH

- As Found: Neuroblastoma

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009447

- Term: Neuroblastoma

### Intervention Browse Module - Ancestors

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1692

- Name: Temozolomide

- Relevance: HIGH

- As Found: Skills

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077204

- Term: Temozolomide

### Misc Info Module

- Version Holder: 2024-05-24
