Phase II Clinical Trial of Patients With High-Grade Glioma Treated With Intra-Arterial Carboplatin-Based Chemotherapy, Randomized to Treatment With or Without Delayed Intravenous Sodium Thiosulfate as a Potential Chemoprotectant Against Severe Thrombocytopenia
试验速览
- 阶段
- 2 期
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with histologically confirmed high-grade glioma are eligible; diagnosis of high-grade glioma will be made on the basis of needle biopsy, open biopsy, or surgical resection
- •Subjects may have had prior focal or systemic radiation or chemotherapy; at least 14 days must have elapsed since radiation treatment and 28 days since prior chemotherapy
- •Performance status (Eastern Cooperative Oncology Group [ECOG]) must be less than or equal to 2 (Karnofsky greater than or equal to 50)
- •White blood cell count >= 2.5 x 10^3/mm^3
- •Absolute granulocyte count >= 1.2 x 10^3/mm^3
- •Platelets >= 100 x 10^3/mm^3
- •Creatinine < 1.8
- •Bilirubin < 2.0
- •Baseline aspartate aminotransferase (AST)/alanine aminotransferase (ALT) serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) must be < 2.5 x institutional upper limits of normal
- •Subject (or legal guardian) must sign a written informed consent in accordance with institutional guidelines
- •Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform the investigator
排除标准
- •Subjects with rapidly progressing central nervous system (CNS) disease with associated neurological deterioration
- •Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failure
- •Subjects who are pregnant, have a positive serum human chorionic gonadotropin (hCG) or are lactating
- •Subjects who have contraindications to carboplatin, cyclophosphamide, etoposide phosphate, or sodium thiosulfate
研究组 & 干预措施
Arm I (combination chemotherapy)
Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm I (combination chemotherapy)
Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm I (combination chemotherapy)
Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Etoposide Phosphate (Drug)
Arm I (combination chemotherapy)
Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm II (combination chemotherapy, sodium thiosulfate)
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 later.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm II (combination chemotherapy, sodium thiosulfate)
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 later.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm II (combination chemotherapy, sodium thiosulfate)
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 later.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Etoposide Phosphate (Drug)
Arm II (combination chemotherapy, sodium thiosulfate)
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 later.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm II (combination chemotherapy, sodium thiosulfate)
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 later.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Sodium Thiosulfate (Drug)
结局指标
主要结局
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
时间窗: Up to 4 weeks after completion of study treatment
The Pearson chi-square test will be the primary test to compare rates.
次要结局
- Number of dose reductions and transfusions due to platelet toxicity(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(Up to 10 years)
- Time to response(Up to 10 years)
- Time to disease progression(Up to 10 years)
- Granulocyte count(Up to 30 days after completion of study treatment)
- Erythrocyte counts(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(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(Up to 60 days after completion of study treatment)
研究者
Edward Neuwelt
Principal Investigator
OHSU Knight Cancer Institute