A Safety Run-in/Randomized Phase II Trial of EMD 121974 in Conjunction With Concomitant and Adjuvant Temozolomide With Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 8
- 主要终点
- Dose Limiting Toxicities of EMD + RT and TMZ
研究概览
简要总结
Cilengitide may stop the growth of cancer by stopping blood flow to the tumor. 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 damage tumor cells. Giving cilengitide together with temozolomide and radiation therapy may kill more tumor cells. This randomized phase I/II trial is studying the side effects and best dose of cilengitide when given together with temozolomide and radiation therapy and to compare how well they work in treating patients with newly diagnosed glioblastoma multiforme
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety profile of EMD 121974 (cilengitide) when administered as a one-hour infusion twice a week concurrently with concomitant and adjuvant temozolomide with radiation therapy for newly diagnosed glioblastoma multiforme. (Safety Run-In)
II. To estimate overall survival in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. (Phase II)
SECONDARY OBJECTIVES:
I. To estimate and compare overall survival between a low dose treatment group and a high dose treatment group in newly diagnosed patients with glioblastoma multiforme treated with EMD 121974 concurrently with concomitant and adjuvant temozolomide with radiation therapy. (Phase II)
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
- 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 must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)
- •Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
- •Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- •Absolute neutrophil count >= 1500/mm^3
- •Platelets >= 100,000/mm^3
- •Creatinine =< 1.5 mg/dl or creatinine clearance >= 60 mL/min
- •Total bilirubin =< 1.5 mg/dl
- •Transaminases =< 4 times above the upper limits of the institutional normal
- •Patients must be able to provide written informed consent
- •Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment
- •Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative pregnancy test
- •Patients must have a Mini Mental State Exam score of >= 15
- •Patients must have tumor tissue form completed and signed by a pathologist
排除标准
- •Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
- •Patients who are pregnant or breast-feeding
- •Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents)
- •Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients who have been free of disease (any prior malignancy) for >= five years are eligible for this study
- •Patients who are unable to undergo an MRI evaluation
- •Patients with a history of wound-healing disorders, advanced coronary disease, or with a recent history (# 1 year) of peptic ulcer disease are ineligible
研究组 & 干预措施
Arm 1 (Safety Run In)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Doses of cilengitide: 500mg, 1000mg and 2000mg
Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: cilengitide (Drug)
Arm 1 (Safety Run In)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Doses of cilengitide: 500mg, 1000mg and 2000mg
Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: temozolomide (Drug)
Arm 1 (Safety Run In)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Doses of cilengitide: 500mg, 1000mg and 2000mg
Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: radiation therapy (Radiation)
Arm 1 (Safety Run In)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Doses of cilengitide: 500mg, 1000mg and 2000mg
Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: laboratory biomarker analysis (Other)
Arm 1 (Safety Run In)
INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Doses of cilengitide: 500mg, 1000mg and 2000mg
Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: pharmacological study (Other)
Phase II (Arm1-500mg)
INITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: cilengitide (Drug)
Phase II (Arm1-500mg)
INITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: temozolomide (Drug)
Phase II (Arm1-500mg)
INITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: radiation therapy (Radiation)
Phase II (Arm1-500mg)
INITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: laboratory biomarker analysis (Other)
Phase II (Arm1-500mg)
INITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: pharmacological study (Other)
Phase II (Arm 2 -2000mg)
INITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: cilengitide (Drug)
Phase II (Arm 2 -2000mg)
INITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: temozolomide (Drug)
Phase II (Arm 2 -2000mg)
INITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: radiation therapy (Radiation)
Phase II (Arm 2 -2000mg)
INITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: laboratory biomarker analysis (Other)
Phase II (Arm 2 -2000mg)
INITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6.
MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study
干预措施: pharmacological study (Other)
结局指标
主要结局
Dose Limiting Toxicities of EMD + RT and TMZ
时间窗: 10 weeks
pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting. Nonhematological toxicities Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)
Maximum Tolerated or Tolerable Dose (MTD) - 3 Pre-defined Doses
时间窗: 10 weeks
pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review any dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (safety run-in) DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting. cohorts at these 3 defined doses: 500mg, 1000mg and 2000mg MTD defined as: dose producing DLT in 2 out of 6 patients or dose level below the dose which produced DLT in \>/= 2 out of 3 patients, or in \>/= 3 out of 6 patients If no MTD (maximum tolerable dose) was defined through 3 steps of dose escalation, phase 2 will proceed with a randomized treatment allocation of the two pre-specified dosage arms: low dose; 500mg and high dose; 2000mg
Overall Survival (Phase II)
时间窗: up to 36 months
The overall survival is calculated from time of histological diagnosis to death occurance - median based on all 112 patients, all dose levels
次要结局
- Frequency of Hematologic and Nonhematologic Adverse Events(Up to 1 year)
- Overall Survival Based on Dose Level - Phase 2(Up to 3 years)