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

• Feasibility of delivering this chemotherapy regimen at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Feasibility defined as the ability to administer induction plus one maintenance cycle
  
  
• Feasibility defined as the ability to administer induction plus four maintenance cycles [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  This is the long-term feasibility endpoint. Defined as the ability to administer induction + four maintenance cycles (i.e., to start the fifth maintenance cycle) within 60 weeks
  
  

• Occurrence of toxic death [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
  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.
  
  
• Grade 3 or 4 thrombocytopenia and/or neutropenia [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
  Grade 3 or 4 thrombocytopenia and/or neutropenia that results in more than a 3 week delay in instituting the next cycle of chemotherapy despite protocol-directed reduction of up to 25% in Carboplatin and/or Temozolomide during the first 60 weeks of therapy
  
  
• Progression-free survival (PFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  Preliminary assessments of treatment efficacy will be based on response to induction therapy, 3-year progression-free survival (PFS)
  
  
• Event-free survival (EFS) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  Preliminary assessments of treatment efficacy will be based on response to induction therapy, 3-year event-free survival(EFS)
  
  
• Response rate categorized as complete response, partial response, stable disease, or progressive disease [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  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.
  
  

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.