Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors
Condition: Brain and Central Nervous System Tumors; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as temozolomide, vincristine, and irinotecan,
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill
      more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when
      given together with temozolomide and vincristine in treating young patients with refractory
      solid tumors.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the maximum tolerated dose and recommended phase II dose of irinotecan when
           administered with temozolomide and vincristine in young patients with refractory solid
           tumors, including brain tumors.

        -  Determine the toxic effects of this regimen in these patients.

        -  Compare the toxic effects of this regimen in patients with low- vs high-risk UGT1A1
           genotypes.

        -  Determine the pharmacokinetics of irinotecan in these patients.

      Secondary

        -  Determine, preliminarily, the antitumor activity of this regimen in these patients.

        -  Correlate UGT1A1, UGT1A7, UGT1A9, and BCRP genotypes with the pharmacokinetics and
           pharmacodynamics of irinotecan and its metabolites in these patients.

      OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified
      according to UGT1A1 genotype (high-risk [7/7 or 6/7 genotype AND bilirubin ≥ 0.6 mg/dL] vs
      low-risk [absence of high-risk criteria]) if a high-risk patient experiences a dose-limiting
      toxicity (DLT).

      Patients receive oral temozolomide on days 1-5 and oral irinotecan on days 1-5 and 8-12.
      Patients also receive vincristine IV over 1 minute on days 1 and 8. Treatment repeats every
      21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
      patients experience DLT.

      After completion of study treatment, patients are followed for 1 month and then annually
      thereafter.

      PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18 months.
    

Intervention name(s): irinotecan hydrochloride; temozolomide; vincristine sulfate
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Irinotecan; Vincristine; Temozolomide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified childhood solid tumor, protocol specific; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood brain stem glioma; recurrent childhood brain tumor; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood visual pathway and hypothalamic glioma; childhood oligodendroglioma; childhood craniopharyngioma; childhood choroid plexus tumor; childhood infratentorial ependymoma; childhood supratentorial ependymoma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebral astrocytoma; childhood central nervous system germ cell tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood subependymal giant cell astrocytoma; childhood atypical teratoid/rhabdoid tumor