This randomized phase II trial studies how well giving combination chemotherapy with or without sodium thiosulfate works in preventing low platelet count while treating patients with malignant brain tumors. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sodium thiosulfate may prevent low platelet counts in patients receiving chemotherapy. It is not yet known whether combination chemotherapy is more effective with or without sodium thiosulfate in preventing low platelet count during treatment for brain tumors.
PRIMARY OBJECTIVE: I. Determine the effect of delayed administration of sodium thiosulfate on the rates of platelet toxicity (i.e. platelet count less than 20,000), in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate. SECONDARY OBJECTIVES: I. Assess tumor response in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate, with or without delayed sodium thiosulfate. II. Assess the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts, in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate. III. Assess hearing changes, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hertz \[Hz\]), and at higher frequencies above standard testing (9000 to 16000 Hz). IV. Assess quality of life in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide phosphate. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cyclophosphamide intravenously (IV), etoposide phosphate IV, and carboplatin intra-arterially (IA) over 10 minutes on day 1. ARM II: Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours after carboplatin. In both arms, treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
48
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
OHSU Knight Cancer Institute
Portland, Oregon, United States
Rate of platelet toxicities (i.e. platelet count less than 20,000), graded according to the National Cancer Institute Common Toxicity Criteria version 3.0
The Pearson chi-square test will be the primary test to compare rates.
Time frame: Up to 4 weeks after completion of study treatment
Number of dose reductions and transfusions due to platelet toxicity
Analyzed using generalized estimating equations and/or a generalized mixed model (for repeated measures analysis of variance) and the third using mixed model repeated measures analysis of variance model.
Time frame: Up to 30 days after completion of study treatment
Tumor response (complete response + partial response + stable disease) assessed by neurologic exams, radiographic studies, and steroid dose
The Pearson chi-square test will be the primary test to compare rates. Comparisons of rates will use the Pearson Chi-square test and logistic regression to adjust for potential confounders.
Time frame: Up to 10 years
Time to response
Descriptive summaries include Kaplan-Meier plots.
Time frame: Up to 10 years
Time to disease progression
Comparisons of time to disease progression will use the log rank test and the Cox proportional hazards model to adjust for potential confounders.
Time frame: Up to 10 years
Granulocyte count
The Pearson chi-square test will be the primary test to compare rates.
Time frame: Up to 30 days after completion of study treatment
Erythrocyte counts
The Pearson chi-square test will be the primary test to compare rates.
Time frame: Up to 30 days after completion of study treatment
Change in hearing levels, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hz), and at higher frequencies above standard testing (9000 to 16000 Hz) based on American Speech-Language-Hearing Association criteria
Descriptive summaries for hearing levels will include means by time and plots of hearing levels by patient over time. The analyses for hearing will include both a time to oto-toxicity (based on American Speech-Language-Hearing Association criteria) comparison using the log rank test and a repeated measure analysis of covariance of the actual hearing levels (with baseline hearing levels as the covariate). Separate analyses will be performed for each hearing frequency with no adjustment for multiple comparisons (as these analyses are descriptive in nature).
Time frame: Baseline up to 30 days after completion of study treatment
Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Quality of Life Questionnaire-Brain Module-20
Summarized by means over time and by plots of values over time for each patient. Quality of life data comparisons between the groups will use repeated measure analysis of covariance (baseline assessment as the covariate).
Time frame: Up to 60 days after completion of study treatment
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