This trial is active, not recruiting.

Conditions brain tumors, central nervous system tumors
Treatments lomustine, temozolomide, adjuvant therapy, radiation therapy
Phase phase 2
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date July 2005
End date September 2012
Trial size 118 participants
Trial identifier NCT00100802, ACNS0423, CDR0000407744, COG-ACNS0423, NCI-2012-02645, U10CA098543


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle.
lomustine Ceenu
temozolomide Temodar
adjuvant therapy
radiation therapy

Primary Outcomes

One year overall survival
time frame: Time to death from any cause, assessed up to 1 year after enrollment
The occurrence of death attributable to complications of protocol therapy
time frame: While receiving protocol therapy or within 30 days of the termination of protocol therapy

Eligibility Criteria

Male or female participants from 3 years up to 21 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.