Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00100802

Purpose

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, 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 temozolomide and lomustine after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: lomustine Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Radiation Therapy

Drug Information available for: Lomustine Temozolomide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Correlation of MGMT and p53 expression in tumor tissue with outcome [ Designated as safety issue: No ]
Correlation of polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in tumors with survival [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	March 2005
Estimated Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.
Determine the toxicity of this regimen in these patients.
Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.
Correlate polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.
Maintenance chemotherapy: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50-100 patients will be accrued for this study within 1-1.5 years.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Gliosarcoma
Primary spinal cord malignant gliomas allowed
No primary brainstem tumors
Has undergone surgical resection or biopsy of the tumor within the past 31 days
- Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries
  - Post-operative MRI not required for patients who undergo biopsy only
No evidence of neuraxis dissemination
- Spine MRI and cerebrospinal fluid cytology required only if clinically indicated

PATIENT CHARACTERISTICS:

Age

3 to 21

Performance status

Karnofsky 50-100% (for patients > 16 years of age)
Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

At least 8 weeks

Hematopoietic

Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3 (transfusion independent)
Hemoglobin ≥ 8 g/dL (transfusions allowed)

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT ≤ 2.5 times ULN
Albumin ≥ 2 g/dL

Renal

Creatinine ≤ 1.5 times ULN OR
Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal

Pulmonary

No evidence of dyspnea at rest
No exercise intolerance
Pulse oximetry ≥ 94% (if determination is clinically indicated)

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 2 months after study participation
Able to swallow oral medication
Seizures allowed provided they are well controlled with anticonvulsants
No hypersensitivity to temozolomide

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior biologic agents

Chemotherapy

No prior chemotherapy

Endocrine therapy

Prior corticosteroids allowed
No concurrent corticosteroids as an antiemetic
Concurrent corticosteroids allowed only for treatment of increased intracranial pressure

Radiotherapy

No concurrent radiotherapy using cobalt-60

Surgery

See Disease Characteristics

Other

No other prior treatment
No concurrent phenobarbital or cimetidine
No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00100802

Show 150 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Regina Jakacki, MD

Children's Hospital of Pittsburgh

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000407744, COG-ACNS0423
Study First Received:	January 6, 2005
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00100802 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

childhood high-grade cerebral astrocytoma
childhood spinal cord neoplasm

Study placed in the following topic categories:

Astrocytoma
Lomustine
Spinal Cord Neoplasm
Adjuvants, Immunologic
Spinal Cord Neoplasms
Antineoplastic Agents, Alkylating

Glioma
Central Nervous System Neoplasms
Alkylating Agents
Temozolomide
Nervous System Neoplasms

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Lomustine
Central Nervous System Neoplasms
Temozolomide
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Nervous System Neoplasms

ClinicalTrials.gov processed this record on August 30, 2009