Radiation Therapy and Combination Chemotherapy in Treating Young Patients With Metastatic Medulloblastoma Who Have Undergone Surgery

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Hyperfractionated Accelerated Radiotherapy (HART) With Chemotherapy (Cisplatin, CCNU, Vincristine) for Metastatic (M1-3) Medulloblastoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00276666
• Other study ID #: CDR0000454549
• Secondary ID: CCLG-CNS-2001-06
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 12, 2006
• Last updated: September 16, 2013
• Start date: November 2001

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as lomustine, vincristine, and cisplatin, 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 together with combination chemotherapy after surgery may kill any tumor cells that remain.

PURPOSE: This phase II trial is studying giving radiation therapy together with combination chemotherapy to see how well it works in treating young patients with metastatic medulloblastoma who have undergone surgery.

Description:

OBJECTIVES:

• Determine the toxicity of hyperfractionated accelerated radiotherapy (HART) in young patients with metastatic medulloblastoma.

• Determine the toxicity of chemotherapy (vincristine during radiotherapy and 8 courses of lomustine, cisplatin, and vincristine after radiotherapy) in association with HART in these patients.

OUTLINE: This is a multicenter study.

• Radiotherapy and vincristine: Beginning 4-6 weeks after surgery, patients undergo hyperfractionated accelerated radiotherapy (HART) twice a day, 5 days a week, for 5 weeks. Patients also receive vincristine IV once weekly for 8 weeks beginning in week 1*. Approximately 6-8 weeks after completion of radiotherapy, patients proceed to maintenance chemotherapy.

NOTE: *The first 7 patients undergo radiotherapy without receiving vincristine

• Maintenance chemotherapy: Patients receive oral lomustine once on day 1 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 5 years.

PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven medulloblastoma

• The following variants of medulloblastoma are also eligible:

• Nodular/desmoplastic medulloblastoma

• Medullomyoblastoma

• Melanotic medulloblastoma

• Metastatic disease, meeting at least 1 of the following criteria:

• Unequivocal evidence on pre- or post-operative MR scan of supratentorial (stage M2) metastases and/or spinal metastases (stage M3)

• Tumor cells seen on cytospin analysis of lumbar cerebral spinal fluid (CSF) (stage M1) performed between 15 days and 21 days after surgery

• Involvement of CSF pathways by tumor is defined as the unequivocal identification of primitive neuroectodermal cells, either on cytological grounds or with a combination of cytological and immunocytological features (e.g., reactivity for GFAP or a neuronal marker, such as synaptophysin)

• Underwent surgery to remove the tumor no more than 6 weeks ago

PATIENT CHARACTERISTICS:

• 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 (1-16 years) or Karnofsky (>16 years) performance status 30-100%

• No active infection

• No prior malignant disease

• Not pregnant or nursing

• No syndrome with recognized potential for increased sensitivity to radiotherapy and/or chromosomal fragility

• Not require anesthesia

• No hearing loss or renal impairment that would make the patient unable to comply with 'Packer' chemotherapy protocol

PRIOR CONCURRENT THERAPY:

• No steroids, if possible, at the start of radiotherapy OR on a stable or reducing dose of steroids during the week before starting radiotherapy

• No prior chemotherapy or radiotherapy

• Dexamethasone should not be used as an anti-emetic unless other therapies fail

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Medulloblastoma
• Nervous System Neoplasms

Intervention

Drug:
• cisplatin

• lomustine

• vincristine sulfate

Procedure:
• adjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Institute of Child Health at University of Bristol	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Cookridge Hospital	Leeds	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	Royal London Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity			Yes