Combination Chemotherapy, Surgery, and Radiation Therapy in Treating Infants With Neuroblastoma

Protocol for Infants With Neuroblastoma Diagnosed Under the Age of One Year

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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. Sometimes, the tumor may not need any treatment until it progresses. In this case, observation may be sufficient.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with surgery and radiation therapy works in treating infants with neuroblastoma.

Study Overview

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

Detailed Description

OBJECTIVES:

• Register all children < 12 months of age diagnosed with neuroblastoma.
• Evaluate possible prognostic factors in these patients with particular reference to the collection of biological material.
• Correlate outcome with factors other than stage in these patients.
• Determine criteria to modify treatment for some children with advanced disease without impairing survival.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 4 treatment groups according to disease stage.

• Group 1 (stage 1, 2A, or 2B disease): Patients undergo surgical resection of the tumor. Patients with paraspinal tumors may receive chemotherapy* to shrink the tumor before undergoing surgery. Patients with local recurrence after surgery proceed to treatment as in group 3. Patients with metastatic recurrence after surgery proceed to treatment as in group 4.
• Group 2 (stage 4S disease): Patients undergo observation only. Patients with hepatomegaly or progressive disease may receive chemotherapy*. Patients who do not respond to chemotherapy may undergo up to 4 courses of radiotherapy.
• Group 3 (stage 3 disease): Patients receive OPEC chemotherapy comprising vincristine IV and cyclophosphamide IV on day 1, cisplatin IV continuously over 24 hours on day 1, and etoposide IV over 4 hours on day 3 during courses 1, 3, and 5. Patients receive OJEC chemotherapy comprising vincristine IV, cyclophosphamide IV, etoposide IV over 4 hours, and carboplatin IV over 1 hour on day 1 during courses 2, 4, and 6. Courses repeat every 3 weeks with alternating OPEC and OJEC chemotherapy for 6 courses. Patients with residual disease then receive 4 additional courses of alternating OPEC and OJEC chemotherapy. Patients whose tumor becomes resectable after either 6 or 10 courses of chemotherapy undergo surgery. Patients with residual disease after 10 courses of chemotherapy are assessed by regular scans. Patients with disease progression on scans undergo radiotherapy. Patients with ganglioneuroma or total necrosis only with no evidence of neuroblastoma after either 6 or 10 courses of chemotherapy receive no further treatment.
• Group 4 (stage 4 disease): Patients receive alternating courses of OPEC and OJEC for 6 courses as in group 3. Patients who do not achieve metastatic complete response (CR) receive 4 additional courses of alternating OPEC and OJEC chemotherapy. Patients achieving metastatic CR after either 6 or 10 courses of chemotherapy undergo surgery to remove the tumor. Patients with macroscopic residual disease on resected specimen receive 4 additional courses of alternating OPEC and OJEC chemotherapy and then undergo biopsy. Patients with residual disease on biopsy are assessed by regular scans. Patients with disease progression on scans undergo radiotherapy. Patients with ganglioneuroma or total necrosis only after surgery with or without the 4 additional courses of chemotherapy receive no further treatment.

NOTE: * OJEC chemotherapy with a lower dose of carboplatin

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

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
    • London, England, United Kingdom, WIT 3AA
      • Meyerstein Institute of Oncology at University College of London Hospitals
    • 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
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Childrens Hospital for Wales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed newly diagnosed neuroblastoma

  • Any stage disease
  • No previously treated disease
  • Must be diagnosed before the first birthday
• Must be able to start treatment before reaching 13 months of age

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

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; Study Chair: Penelope Brock, MD, PhD, University College London Hospitals; Mary P. Gerrard, MBChB, FRCP, FRCPCH, Children's Hospital - Sheffield; Ann Barrett, University of Glasgow

Study record dates

Study Major Dates

• Study Start: September 1, 1992

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 7, 2006

Study Record Updates

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

More Information

Terms related to this study

• Keywords: disseminated neuroblastoma; localized unresectable neuroblastoma; stage 4S 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: CDR0000454726; CCLG-1992-05; EU-20593; CCLG-9205