Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- RP2D for DMF when combined with concurrent temozolomide and radiotherapy determined by the incidence of dose limiting toxicities (DLTs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
研究概览
简要总结
This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Dimethyl fumarate may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Drugs used in chemotherapy, such as temozolomide, 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving dimethyl fumarate with temozolomide and radiation therapy may work better in treating glioblastoma multiforme.
详细描述
PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) of dimethyl fumarate (DMF) when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed glioblastoma multiforme (GBM).
SECONDARY OBJECTIVES:
I. To evaluate the safety, tolerance, and toxicity of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.
II. To obtain a preliminary estimate of the efficacy of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) following either a surgical resection or biopsy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Subjects must have recovered from surgery or biopsy before study registration
- •Therapy must begin between 21 days (3 weeks) and 42 days (6 weeks) after the most recent brain tumor surgery(resection or biopsy)
- •Documentation of steroid doses 10-14 days prior to study registration and stable or decreasing steroid dose over the week prior to registration
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •Platelets >= 100,000/mm^3 (untransfused)
- •Hemoglobin >= 10 g/dL (the use of transfusion or other intervention to achieve hemoglobin >= 10 g/dL is acceptable)
- •Creatinine =< 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance > 45 mL/min
- •Total bilirubin =< 1.5 x ULN for the laboratory (total bilirubin criteria may be waived if a subject has documented Gilbert's syndrome)
- •Aspartate aminotransferase (AST) =< 3 x ULN for the laboratory
- •Alanine aminotransferase (ALT) =< 3 x ULN for the laboratory
- •Women of childbearing potential and male subjects must practice adequate contraception
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Prior invasive malignancy (except for non-melanoma skin cancer) unless disease free for >= 3 years
- •Recurrent malignant gliomas
- •Metastases detected below the tentorium or beyond the cranial vault
- •Prior chemotherapy or radiation therapy (RT) for the diagnosis of GBM or for cancers of the head and neck
- •Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy
- •Pregnant or lactating women
- •History of allergic reactions or intolerance to any of the required agents on the study
- •History of hypersensitivity to dacarbazine
- •Any treatment for GBM, other than surgery or anti-epileptic therapy, within 30 days prior to study treatment initiation
- •Other condition(s) that in the opinion of the investigator might compromise the objectives of the study or increase patient risk
研究组 & 干预措施
Treatment (dimethyl fumarate, temozolomide, radiation therapy)
CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide PO QD for 42-49 days and dimethyl fumarate PO BID or TID continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions
MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Dimethyl Fumarate (Drug)
Treatment (dimethyl fumarate, temozolomide, radiation therapy)
CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide PO QD for 42-49 days and dimethyl fumarate PO BID or TID continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions
MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Temozolomide (Drug)
Treatment (dimethyl fumarate, temozolomide, radiation therapy)
CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide PO QD for 42-49 days and dimethyl fumarate PO BID or TID continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions
MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
结局指标
主要结局
RP2D for DMF when combined with concurrent temozolomide and radiotherapy determined by the incidence of dose limiting toxicities (DLTs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
时间窗: Up to 6 weeks
Subjects' treatment dosing level, dose modification, DLTs, and evaluability for DLTs and response will be listed and summarized by basic descriptive statistics (such as frequency and proportion).
次要结局
- Progression free survival (PFS)(Time from registration to time of symptomatic and/or radiographic progression or death, whichever occurs first, assessed up to 2 years)
- Overall survival (OS)(Time from registration until death from any cause, assessed up to 2 years)
- Incidence of adverse events graded according to NCI CTCAE version 4.0(Up to 30 days after completion of treatment)
- Response rate assessed as per the Response Assessment in Neuro-oncology for magnetic resonance imaging scans or Macdonald criteria for computed tomography scans(Up to 2 years)