Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas
This study has been completed.
Sponsor:
Children's Oncology Group
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00100802
First received: January 6, 2005
Last updated: March 6, 2013
Last verified: March 2013
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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 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: 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:
Further study details as provided by Children's Oncology Group:
Primary Outcome Measures:
- Event-free survival [ Time Frame: Time to disease progression, disease relapse, occurence of a second malignant neoplasm, or death from any cause assessed at 1 year ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Cumulative incidence of toxic death primarily attributable to complications of treatment
| Enrollment: | 118 |
| Study Start Date: | March 2005 |
| Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Surgery, Chemoradiotherapy, Rest, Maintneance, FUP
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/m 2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temolomide. 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.
|
Drug: lomustine
Capsule
Other Names:
Drug: temozolomide
Capsule
Other Names:
Procedure: adjuvant therapy
Radiation: radiation therapy
|
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
Show 150 Study LocationsSponsors and Collaborators
Children's Oncology Group
Investigators
| Study Chair: | Regina Jakacki, MD | Children's Hospital of Pittsburgh of UPMC |
More Information
Additional Information:
Publications:
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00100802 History of Changes |
| Other Study ID Numbers: | ACNS0423, CDR0000407744, COG-ACNS0423 |
| Study First Received: | January 6, 2005 |
| Last Updated: | March 6, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Children's Oncology Group:
|
childhood high-grade cerebral astrocytoma childhood spinal cord neoplasm |
Additional relevant MeSH terms:
|
Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Neoplasms Nervous System Diseases Lomustine Temozolomide |
Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013