PHASE I-II TRIAL OF METRONOMIC TEMOZOLAMIDE WITH INTERMITTENT INTENSIFICATION AND IRINOTECAN IN PATIENTS WITH RECURRENT GLIOBLASTOMA
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 30
- 主要终点
- Efficacy of the treatment (Phase I)
研究概览
简要总结
Indication:
Subjects with glioblastoma at first relapse after surgery, radiotherapy and first-line temozolomide (TMZ).
Objectives:
- Phase I endpoint:
- To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous, and metronomic regimen of TMZ, given in 28-day cycles.
- Phase II endpoints:
Primary endpoint: Progression-free survival at 6 months. Secondary endpoints: Response rate, toxicity profile, overall survival.
Complementary studies:
To assess the effect of treatment on plasma concentration of thrombospondin-1 (TSP1), soluble VEGF receptor 1 (sVEGF-1) and VEGF-A, and their correlation with clinical outcome.
- To assess the correlation between immunohistochemical expression of PTEN and MGMT proteins, and clinical outcomes.
详细描述
Study Design: Open label, phase I - II trial. Phase I trial: TMZ will be administered in a fixed schedule as follows:
TMZ
- 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
- 100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
.100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ.(Level 1).One cycle = 28 days. CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Patients > 18 years old
- •Histological confirmed GB at first relapse, assessed by MRI scan, after surgical resection or biopsy, radiotherapy, and first-line chemotherapy with TMZ. A TMZ treatment duration of at least 3 months is required. Previous chemotherapy with CPT-11 is not allowed.
- •Karnofsky performance status ≥
- •ANC ≥ 1500/ μl, platelet count ≥ 100000/ μl, haemoglobin > 10 g/dl, serum creatinine and total bilirubin < 1.5 times the upper limit of laboratory normal, transaminases < 3.0 times the upper limit of laboratory normal.
- •Stable or descending corticosteroid dose ≥ 72 hours before baseline MRI and study treatment.
- •Life expectancy greater than 3 months
- •Written informed consent.
排除标准
- •Pregnancy or breastfeeding.
- •Neurological impairment that precludes comprehension or treatment administration
- •Vomiting or other condition that interfere with oral administration of TMZ
- •Previous or concurrent malignancy, excluding basal cell carcinomas or in situ cervical cancer.
- •Concurrent disease that could interfere with treatment
- •Concurrent treatment with enzyme-inducing drugs. Patients under enzyme-inducing anticonvulsants should discontinue treatment at least one week before study treatment and begin a new anti-epileptic treatment with non enzyme-inducing drugs if indicated.
研究组 & 干预措施
Temozolamide, irinotecan
Phase I trial:
TMZ will be administered in a fixed schedule as follows:
TMZ 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ. (Level 1)
One cycle = 28 days
CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 .
干预措施: Temozolamide, irinotecan (Drug)
结局指标
主要结局
Efficacy of the treatment (Phase I)
时间窗: every patient should receive at least one cycle ( 28 days)
To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous and metronomic regimen of TMZ, given in 28-days cycles to use the Recommended Dose in phase II
Progression-free survival (Phase II)
时间窗: Since the initial of the treatment until the patient progression
The time the patient is not in progression, since the beginning of the treatment
次要结局
- Assess the toxicity of the treatment(the patients will be followed until disease progression)
- Progression-free survival at 6 months(6 months since the pacient is included in the trial)
- overall survival(the patients will be followed until death)