Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin, vincristine, and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells. PURPOSE: This pilot study is studying giving carboplatin and vincristine together with temozolomide in treating children with progressive and/or symptomatic low-grade glioma.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility and toxicity of an induction and maintenance regimen comprising carboplatin, vincristine, and temozolomide in children with progressive and/or symptomatic low-grade gliomas. Secondary Determine response rate in patients treated with this regimen. Determine 3-year progression-free survival and overall survival of patients treated with this regimen. Correlate response and progression-free survival with the genomic profile of tumors in patients treated with this regimen. OUTLINE: This is a pilot study. Induction therapy: Patients receive carboplatin IV over 1 hour on days 1, 8, 15, and 22; vincristine IV on days 1, 8, 15, 22, 29, and 36; and oral temozolomide on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin and temozolomide as in induction therapy and vincristine IV on days 1, 8, and 15. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 2 years.

Official Title
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A Pilot Study Using Carboplatin, Vincristine And Temozolomide For Children ≤ 10 Years With Progressive/Symptomatic Low-Grade Gliomas

Conditions
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Brain Tumor, Central Nervous System Tumor

Intervention / Treatment
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* Drug: carboplatin
* Drug: temozolomide
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed progressive and/or symptomatic low-grade glioma, including any of the following: WHO grade I or II astrocytoma Grade I or II oligodendrogliomas Mixed oligodendrogliomas Gangliogliomas Measurable disease Progressive and/or symptomatic supratentorial or spinal cord tumors that cannot be removed for anatomical reasons are allowed Optic pathway tumors allowed provided there is evidence of progressive disease by MRI and/or symptoms of deteriorating vision, progressive hypothalamic/pituitary dysfunction, or diencephalic syndrome Dorsally exophytic brainstem gliomas that were previously resected more than 50% are allowed provided the residual tumor shows progression (with or without symptoms) No diffuse brain stem tumors No type 1 neurofibromatosis PATIENT CHARACTERISTICS: Age 10 and under Performance status ECOG 0-2 Lansky 50-100% Life expectancy Not specified Hematopoietic Hemoglobin ≥ 8.0 gm/dL Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT < 2.5 times ULN Renal Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR Creatinine ≤ 0.8 mg/dL (age 5 and under) OR ≤ 1.0 mg/dL (age 6 to10) Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunomodulating agents Chemotherapy No other concurrent anticancer chemotherapy Endocrine therapy Prior corticosteroids allowed No concurrent corticosteroids except for the treatment of increased intracranial pressure Radiotherapy Not specified Surgery See Disease Characteristics Prior surgery allowed Other No other prior therapy

Ages Eligible for Study
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Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (carboplatin, vincristine sulfate, temozolomide)<br>Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. | Drug: carboplatin<br>* Given IV<br>* Other names: NSC #241240;Drug: temozolomide<br>* Given orally<br>* Other names: NSC# 362856;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Term Feasibility Success | Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure. | 24 weeks | 
| Long Term Feasibility Success | Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success. | 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Toxic Death | Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin. | Up to 6 years after the start of protocol therapy | 
| Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia. | Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy. | Up to 18 months of protocol therapy | 
| Percent Probability of Progression-free Survival (PFS) | Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment. | 3 years | 
| Percentage Probability of Event-free Survival (EFS) | Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment. | Six years | 
| Total Number of Patients Experiencing a Response | Response as complete response, partial response, stable disease, or progressive disease using three-dimensional imaging measurements (preferable) or two-dimensional imaging measurements, as well as the response in the context of multiple lesions or disseminated disease. | Up to 18 months of protocol therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated childhood cerebellar astrocytoma, untreated childhood visual pathway and hypothalamic glioma, childhood spinal cord neoplasm, childhood oligodendroglioma, childhood low-grade cerebral astrocytoma