Clinical trial NCT00276731: Combination Chemotherapy Followed By Surgery With or Without Radiation Therapy in Treating Young Patients With Stage II or Stage III Neuroblastoma
Official title: Randomized Study of Radiotherapy in Patients With Stage 2B/3 (INSS) Neuroblastoma in Children Over 1 Year of Age
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Neuroblastoma
Keywords: localized resectable neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-01-13
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy 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. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain. It is not yet know whether combination chemotherapy followed by surgery alone is more effective than combination chemotherapy followed by surgery and radiation therapy in treating neuroblastoma.

PURPOSE: This randomized phase III trial is studying combination chemotherapy followed by surgery to see how well it works compared to combination chemotherapy followed by surgery and radiation therapy in treating young patients with stage II or stage III neuroblastoma.

Detailed description: OBJECTIVES:

* Compare the local control and event-free and overall survival of young patients with stage IIB and III neuroblastoma treated with neoadjuvant combination chemotherapy followed by surgery with vs without radiotherapy.
* Determine the toxic effects of these regimen in these patients.

OUTLINE: This is a multicenter, randomized study.

* Induction combination chemotherapy: Patients receive vincristine IV and cyclophosphamide IV on day 1. Patients also receive cisplatin IV continuously over 24 hours on day 1 and etoposide IV over 4 hours on day 2 during courses 1, 3, and 5 and carboplatin IV over 1 hour and etoposide IV over 4 hours on day 1 during courses 2 and 4. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to surgery unless complete resection was done during initial staging and complete response was maintained.
* Surgery: Patients undergo biopsy or surgical resection of the tumor 2-3 weeks after completion of induction combination chemotherapy.
* Post-surgical treatment: Patients are randomized to 1 of 2 treatment arms.

  * Arm I: Patients receive two additional courses of combination chemotherapy comprising vincristine, cisplatin, etoposide, and cyclophosphamide in course 6 and vincristine, carboplatin, etoposide, and cyclophosphamide in course 7.
  * Arm II: Patients undergo radiotherapy 2-4 weeks after surgery. Beginning 3 weeks after completion of radiotherapy, patients receive chemotherapy as in arm I After completion of study treatment, patients are evaluated periodically.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed stage IIB or III neuroblastoma

  * No n-myc amplification

PATIENT CHARACTERISTICS:

* Not specified

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy or radiotherapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
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: Beatson Oncology Centre
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: University of Glasgow
name: Ann Barrett
role: STUDY_CHAIR
affiliation: St. George's Hospital
name: S. J. Keith Holmes, DO
affiliation: University Hospital Southampton NHS Foundation Trust
name: Janice A. Kohler, MD, FRCP
affiliation: University of Newcastle Upon-Tyne
name: Andrew David J. Pearson, MD, FRCP, DCh
affiliation: Yale University
name: Jack van Hoff, MD
affiliation: University of Alabama at Birmingham
name: Robert P. Castleberry, MD
affiliation: Mercy Regional Cancer Center at Mercy Medical Center
name: Kevin Murray, MD
References: