Efficacy and Safety of Low Dose Temozolomide Plus Metformin as Combination Chemotherapy Compared With Low Dose Temozolomide Plus Placebo in Patient With Recurrent or Refractory Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 81
- 试验地点
- 12
- 主要终点
- Comparison of progression-free survival obtained from progression-free survival curve
研究概览
简要总结
A phase 2 clinical trial for the efficacy and safety of low dose Temozolomide plus metformin as combination chemotherapy compared with low dose Temozolomide plus placebo in patient with recurrent or refractory Glioblastoma
详细描述
Studies will investigate the efficacy and safety of low dose Temozolomide with Metformin or placebo for the patients with recurrent or refractory Glioblastoma.
The dosage of the Metformin will follow the domestically permitted dose to minimize side effects.
The patients will be allocated randomly to arm 1(experimental) and arm 2(placebo controlled) and administered the investigational products for up to 6 cycle. Each cycle consists of 4 weeks.
After 6 cycle(24 weeks), the patients will be checked progression and survival every 24 weeks up to 96 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blinded
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Progressive or recurrent Glioblastoma conformed by histopathological or radiological diagnosis. Progressive or recurrent Glioblastoma during or after standard therapy (Temozolomide after Temozolomide and radiation therapy; Stupp regimen) after histopathological diagnosis of Glioblastoma Recurrence or progression is diagnosed according to histopathological diagnosis or revised RANO(Response Assessment in Neuro-Oncology) criteria c
- •Karnofsky performance status(KPS) ≥ 60%
- •Age ≥ 19 years old
- •At least 4 weeks after operation or chemotherapy
- •Normal in hematological finding, liver and kidney function
- •Hematology ANC > 1.500/mm³, Platelet > 100,000/mm³, WBC > 3×10^9/L, Hemoglobin > 9g/dL
- •Liver function Total Bilirubin level ≤ 1.5×ULN(in case of isolated hyperbilirubinemia ≤2.5 x ULN) AST / ALT < 2.5×ULN
- •Renal function Serum creatinine ≤ 1.5mg/dL
- •Be informed of the nature of the study and obtained a written informed consent
- •A legal representative agrees to the trial when a subject is unable to communicate smoothly due to neurologic defect
- •If a fertile woman who has been confirmed negative to a urine or blood pregnancy test within 28 days prior to the trial
排除标准
- •Pregnant or breast feeding
- •Cancer history within 5 years excluding cancer in the skin cells and cervix
- •Active infections within two weeks
- •Leptomeningeal metastasis
- •Patients diagnosed with diabetes
- •Hypersensitive or intolerance to Metformin
- •Patients who are currently taking Metformin, sulfonylureas, thiazolidinediones, and insulin, regardless of reason
- •Other serious diseases or medical conditions that include :
- •Patients who suffer from unstable heart disease despite treatment.
- •Patients having a heart attack within 6 months prior to the start of trial
- •Patients who suffer from severe nerve or psychosis that includes dementia or strokes.
- •Patients with an uncontrolled infection
- •Patient with uncontrolled hypertension, congestive heart failure, unstable angina, or incomplete arrhythmia
- •Those who have participated in other clinical trials may not recover from the toxicity of the treatment.
研究组 & 干预措施
Temozolomide+metformin
Temozolomide :
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks
Metformin :
- 1st cycle (4 weeks)
- 1 week(1st~7th day) = 1,000mg/day
- 1 week(8th~14th day) = 1,500mg/day
- 2 weeks(15th ~28th day) = 2,000mg/day
- 2nd to 6th cycle (20 weeks) = 2,000mg/day
干预措施: Temozolomide+Metformin (Drug)
Temozolomide+placebo
Temozolomide :
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks
Placebo:
- 1st cycle (4 weeks)
- 1 week(1st~7th day) = 1,000mg/day
- 1 week(8th~14th day) = 1,500mg/day
- 2 weeks(15th~28th day) = 2,000mg/day
- 2nd to 6th cycle (20 weeks) = 2,000mg/day
干预措施: Temozolomide+Placebo (Drug)
结局指标
主要结局
Comparison of progression-free survival obtained from progression-free survival curve
时间窗: 24 weeks
Comparison of progression-free survival obtained from progression-free survival curve
次要结局
- Tumor control probability(4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks)
- 6 month progression free survival(24 weeks)
- Response Rate(4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks)
- Assessment of the quality of life of cancer patients(4 weeks, 8 weeks, 16 weeks, 24 weeks)
- 6 month overall survival(24 weeks)
研究者
Yong-Kil Hong
MD., PhD.
Seoul St. Mary's Hospital