Combination Chemotherapy Followed By Surgery With or Without Radiation Therapy in Treating Young Patients With Stage II or Stage III Neuroblastoma

Randomized Study of Radiotherapy in Patients With Stage 2B/3 (INSS) Neuroblastoma in Children Over 1 Year of Age

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.

Study Overview

• Status: Unknown
• Conditions: Neuroblastoma
• Intervention / Treatment: Drug: carboplatin; Drug: cyclophosphamide; Radiation: radiation therapy; Drug: etoposide; Drug: vincristine sulfate; Procedure: neoadjuvant therapy; Drug: cisplatin; Procedure: conventional surgery

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 12
    • Our Lady's Hospital for Sick Children
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B4 6NH
      • Birmingham Children's Hospital
    • Bristol, England, United Kingdom, BS2 8AE
      • Institute of Child Health at University of Bristol
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • Liverpool, England, United Kingdom, L12 2AP
      • Royal Liverpool Children's Hospital, Alder Hey
    • London, England, United Kingdom, E1 1BB
      • Royal London Hospital
    • London, England, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children NHS Trust
    • Manchester, England, United Kingdom, M27 4HA
      • Central Manchester and Manchester Children's University Hospitals NHS Trust
    • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
      • Sir James Spence Institute of Child Health
    • Nottingham, England, United Kingdom, NG7 2UH
      • Queen's Medical Centre
    • Oxford, England, United Kingdom, 0X3 9DU
      • Oxford Radcliffe Hospital
    • Sheffield, England, United Kingdom, S10 2TH
      • Children's Hospital - Sheffield
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust - Surrey
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT12 6BE
      • Royal Belfast Hospital for Sick Children
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZG
      • Royal Aberdeen Children's Hospital
    • Edinburgh, Scotland, United Kingdom, EH9 1LF
      • Royal Hospital for Sick Children
    • Glasgow, Scotland, United Kingdom, G3 8SJ
      • Royal Hospital for Sick Children
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Beatson Oncology Centre
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Childrens Hospital for Wales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Children's Cancer and Leukaemia Group
• Investigators: Andrew David J. Pearson, MD, FRCP, DCh, University of Newcastle Upon-Tyne; S. J. Keith Holmes, DO, St. George's Hospital; Janice A. Kohler, MD, FRCP, University Hospital Southampton NHS Foundation Trust; Jack van Hoff, MD, Yale University; Robert P. Castleberry, MD, University of Alabama at Birmingham; Kevin Murray, MD, Mercy Regional Cancer Center at Mercy Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 1995

Study Registration Dates

• First Submitted: January 12, 2006
• First Submitted That Met QC Criteria: January 12, 2006
• First Posted (Estimate): January 13, 2006

Study Record Updates

• Last Update Posted (Estimate): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: January 1, 2006

More Information

Terms related to this study

• Keywords: localized unresectable neuroblastoma; regional neuroblastoma; localized resectable neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Carboplatin; Etoposide; Vincristine
• Other Study ID Numbers: CDR0000454725; CCLG-NB-1995-02; EU-20595; UKCCSG-ENSG-9