A Phase I Study of CCI-779, and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 11
- 主要终点
- Maximally tolerated dose (MTD), determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
研究概览
简要总结
This phase I trial is studying the side effects and best dose of temsirolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temsirolimus together with temozolomide and radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of temsirolimus when administered with temozolomide in combination with radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
II. Assess and describe the adverse events associated with this regimen in these patients.
III. Evaluate the early response to therapy in these patients using an automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging.
SECONDARY OBJECTIVES:
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
- •Histologically confirmed glioblastoma multiforme (GBM)
- •Gliosarcoma and other grade 4 astrocytoma variants (e.g., giant cell glioblastoma) allowed
- •Newly diagnosed disease
- •Has undergone surgical resection or biopsy of the tumor at least 1 week but no more than 6 weeks ago
- •ECOG performance status 0-2
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Hemoglobin ≥ 9.0 g/dL
- •Platelet count ≥ 100,000/mm^3
- •Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
- •Cholesterol < 350 mg/dL
- •Triglycerides < 400 mg/dL
- •AST ≤ 2.5 times ULN
- •Creatinine ≤ 1.5 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergy or intolerance to dacarbazine
- •No ongoing or active infection
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled illness
- •No gastrointestinal tract disease affecting ability to take oral medication or requiring IV alimentation
- •No significant traumatic injury within the past 21 days
- •No active, uncontrolled peptic ulcer disease
- •No other active cancers requiring therapy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •Willing and able to comply with antibiotic prophylaxis with either trimethoprim/sulfamethoxazole (daily or 3 times per week) or monthly IV pentamidine combined with daily levofloxacin
- •No prior chemotherapy for any brain tumor
- •No prior temozolomide or mTOR inhibitor therapies
- •No prior cranial radiotherapy
- •More than 21 days since prior major surgery (excluding neurosurgical biopsy or resection of GBM)
- •No prior surgical procedures affecting absorption
- •No concurrent enzyme-inducing anticonvulsants, including any of the following:
- •Carbamazepine
- •Phenytoin
- •Phenobarbital
- •Primidone
- •No other concurrent investigational agents
- •Not receiving warfarin prior to study registration
- •Concurrent warfarin allowed if patients develop an indication for it while enrolled on the protocol
排除标准
- 未提供
研究组 & 干预措施
Treatment (temsirolimus, temozolomide, radiation therapy)
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (temsirolimus, temozolomide, radiation therapy)
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: adjuvant therapy (Procedure)
Treatment (temsirolimus, temozolomide, radiation therapy)
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: 3-dimensional conformal radiation therapy (Radiation)
Treatment (temsirolimus, temozolomide, radiation therapy)
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: intensity-modulated radiation therapy (Radiation)
Treatment (temsirolimus, temozolomide, radiation therapy)
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temsirolimus (Drug)
Treatment (temsirolimus, temozolomide, radiation therapy)
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temozolomide (Drug)
结局指标
主要结局
Maximally tolerated dose (MTD), determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
时间窗: Up to 24 weeks
Time to treatment related toxicity as assessed by hematologic measures and CTCAE v3.0
时间窗: From registration to documentation of toxicity, up to 5 years
Time to treatment related toxicity greater than grade 3, assessed by CTCAE v3.0
时间窗: From registration to documentation of toxicity, up to 5 years
Time to progression
时间窗: From registration to documentation of progression, up to 5 years
Time to treatment failure
时间窗: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by patient, up to 5 years
Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals.The effect of dose and ancillary dichotomized covariates such as gender or age (\<50 years versus 50+ years) will be explored using logrank testing involving one covariate at a time.
Response to therapy associated with patient outcome, as assessed by automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging
时间窗: Up to 5 years
Logistic regression and Cox proportional hazards models will be used to determine the association between changes in tumor volume (as assessed by a software package) and tumor response and 12-month survival (logistic regression) and progression-free and overall survival (Cox proportional hazards models).
次要结局
未报告次要终点