Radiation Therapy Followed By Combination Chemotherapy in Treating Young Patients With Supratentorial Primitive Neuroectodermal Tumors

Hyperfractionated Accelerated Radiotherapy (HART) With Chemotherapy (Cisplatin, CCNU, Vincristine) for Non-Pineal Supratentorial Primitive Neuroectodermal Tumours

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as lomustine, cisplatin, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy followed by combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy followed by combination chemotherapy works in treating young patients with supratentorial primitive neuroectodermal tumors.

Study Overview

• Status: Unknown
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Radiation: radiation therapy; Drug: vincristine sulfate; Procedure: adjuvant therapy; Drug: cisplatin; Drug: lomustine

Detailed Description

OBJECTIVES:

Primary

• Determine the toxicity of hyperfractionated accelerated radiotherapy (HART) in pediatric patients with nonpineal supratentorial primitive neuroectodermal tumors.

Secondary

• Determine overall and relapse-free survival of patients treated with HART followed by adjuvant combination chemotherapy comprising lomustine, cisplatin, and vincristine.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Radiotherapy: Patients undergo hyperfractionated accelerated radiotherapy (HART) twice a day, 5 days a week, for 5 weeks.
• Adjuvant combination chemotherapy: Six weeks after the last radiotherapy dose, patients receive oral lomustine once and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 . Treatment repeats every 6 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 12
    • Our Lady's Hospital for Sick Children Crumlin
• 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
    • 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
    • Manchester, England, United Kingdom, M27 4HA
      • Royal Manchester Children's Hospital
    • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
      • Sir James Spence Institute of Child Health at Royal Victoria Infirmary
    • 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 - 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: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven nonpineal supratentorial primitive neuroectodermal tumors

  • No supratentorial atypical teratoid/rhabdoid tumors or medulloepitheliomas

• Localized or metastatic disease

  • Metastatic disease is defined as unequivocal evidence of supratentorial metastases and/or spinal metastases on pre-operative or postoperative MRI scan OR tumor cells seen on cytospin analysis of lumbar cerebrospinal fluid (stage M1) performed between 15 days and 21 days after surgery
• Has undergone surgical resection within the past 4-6 weeks

PATIENT CHARACTERISTICS:

• Able to cooperate with twice daily fractions of radiotherapy
• Hemoglobin ≥ 10 g/dL
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Neurologically stable (or improving) during the week before starting radiotherapy
• Lansky performance status 30-100% (for patients 1 to 16 years of age) OR
• Karnofsky performance status 30-100% (for patients over 16 years of age)
• Must be able to comply with the chemotherapy protocol (e.g., no hearing loss, renal impairment)
• No presence of active uncontrolled infection
• No previous malignant disease
• Not pregnant or nursing
• No syndrome with recognized potential for increased sensitivity to radiotherapy and/or chromosomal fragility

PRIOR CONCURRENT THERAPY:

• No previous chemotherapy or radiotherapy
• The patient should not be receiving steroids, if possible, at the start of radiotherapy or should be on a stable or reducing dose of steroids during the week before starting radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity measured by hematological, gastrointestinal, mucosal, neurological, and skin morbidity during treatment and for 6 weeks after completion of treatment

Secondary Outcome Measures

Outcome Measure
Overall and relapse free survival at follow up every 2 months for 1 year, every 3 months for 2 years, and then every 6 months for 2 years

Collaborators and Investigators

• Sponsor: Children's Cancer and Leukaemia Group
• Investigators: Barry Pizer, MD, Royal Liverpool Children's Hospital, Alder Hey; David Ellison, MD, Northern Centre for Cancer Treatment at Newcastle General Hospital; Study Chair: Frank Saran, MD, Royal Marsden NHS Foundation Trust; Christopher Chandler, MD, King's College Hospital NHS Trust; Roger Taylor, MD, Cookridge Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Anticipated): March 1, 2010

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (Estimate): January 11, 2006

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: untreated childhood supratentorial primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Vincristine; Lomustine
• Other Study ID Numbers: CCLG-CNS-2004-01; CDR0000454540 (Registry Identifier: PDQ (Physician Data Query)); EU-20580