NCT00813943已完成2 期
Cilengitide in Subjects With Newly Diagnosed Glioblastoma and Unmethylated MGMT Gene Promoter - a Multicenter, Open-label Phase II Study, Investigating Two Cilengitide Regimens in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy). [The CORE Study]
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- EMD Serono
- 入组人数
- 265
- 试验地点
- 2
- 主要终点
- Overall Survival (OS) Time
研究概览
简要总结
CORE is a Phase 2 clinical trial in newly diagnosed glioblastoma in subjects with an unmethylated O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) gene promoter in the tumor tissue.
The MGMT gene promoter is a section of deoxyribonucleic acid (DNA) that acts as a controlling element in the expression of MGMT. Methylation of the MGMT gene promoter has been found to appear to be a predictive marker for benefit from temozolomide (TMZ) treatment.
In a safety run-in period in dedicated study centers, the safety and tolerability of Cilengitide given as an intense treatment in combination with the first part of standard therapy will be assessed. Thereafter the trial will investigate the overall survival and progression-free survival in subjects receiving two different regimens of Cilengitide in combination with standard treatment versus standard treatment alone.
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
- •Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization [WHO] Grade IV, including glioblastoma subtypes, for example, gliosarcoma). The histological diagnosis has to be obtained from a neurosurgical resection of the tumor or by an open biopsy (stereotactic biopsy is not allowed)
- •Tumor tissue specimens from the glioblastoma surgery or open biopsy (formalin-fixed paraffin-embedded) must be available for MGMT gene promoter status analysis and central pathology review
- •Proven unmethylated MGMT gene promoter status (that is, cut-off ratio less than (<) 2 by means of applied test to determine MGMT gene promoter status)
- •Males or females greater than or equal to (>=) 18 years of age
- •Interval of >= 2 weeks but less than or equal to (=<) 7 weeks after surgery or biopsy before first administration of study treatment
- •Available post-operative gadolinium-enhanced magnetic resonance imaging (Gd-MRI) performed within < 48 hours after surgery
- •Stable or decreasing dose of steroids for >= 5 days prior to randomization
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
- •Has to meet 1 of the following recursive partitioning analysis (RPA) classifications:
- •Class III (Age < 50 years and ECOG PS 0)
- •Class IV (meeting one of the following criteria: a) Age < 50 years and ECOG PS 1 or b) Age >= 50 years, underwent prior partial or total tumor resection, Mini Mental State Examination [MMSE] >= 27)
- •Class V (meeting one of the following criteria: a) Age >= 50 years and underwent prior partial or total tumor resection, MMSE < 27 or b) Age >= 50 years and underwent prior tumor biopsy only)
- •Other protocol defined inclusion criteria could apply
排除标准
- •Prior chemotherapy within the last 5 years
- •Prior RTX of the head (except for low dose RTX for tinea capitis)
- •Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide
- •Prior systemic anti-angiogenic therapy
- •Placement of Gliadel® wafer at surgery
- •Planned surgery for other diseases
- •History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment
- •History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for >= 5 years are eligible for this study
- •History of coagulation disorder associated with bleeding or recurrent thrombotic events
- •Clinically manifest myocardial insufficiency (New York Heart Association [NYHA] III, IV) or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension
- •Inability to undergo Gd-MRI
- •Concurrent illness, including severe infection (for example, human immunodeficiency virus), which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety
- •Subject is pregnant (positive serum beta human chorionic gonadotropin [b-HCG] test at screening) or is currently breast-feeding, anticipates becoming pregnant/impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment
- •Current alcohol dependence or drug abuse
- •Known hypersensitivity to the study treatment
- •Legal incapacity or limited legal capacity
- •Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Temozolomide + Radiotherapy
Active Comparator
干预措施: Radiotherapy (Radiation)
Cilengitide (2-times weekly) + Temozolomide + Radiotherapy
Experimental
干预措施: Cilengitide (2-times weekly) (Drug)
Cilengitide (2-times weekly) + Temozolomide + Radiotherapy
Experimental
干预措施: Temozolomide (Drug)
Cilengitide (2-times weekly) + Temozolomide + Radiotherapy
Experimental
干预措施: Radiotherapy (Radiation)
Cilengitide (5-times weekly) + Temozolomide + Radiotherapy
Experimental
干预措施: cilengitide (5-times weekly) (Drug)
Cilengitide (5-times weekly) + Temozolomide + Radiotherapy
Experimental
干预措施: Temozolomide (Drug)
Cilengitide (5-times weekly) + Temozolomide + Radiotherapy
Experimental
干预措施: Radiotherapy (Radiation)
Temozolomide + Radiotherapy
Active Comparator
干预措施: Temozolomide (Drug)
结局指标
主要结局
Overall Survival (OS) Time
时间窗: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, Jun 2009 until cut-off date, (07 Feb 2013)
The OS time is defined as the time (in months) from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
次要结局
- Progression Free Survival (PFS) Time - Investigator and Independent Read(Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, Jun 2009 until cut-off date, (07 Feb 2013))
- Apparent Terminal Rate Constant(Days 1 and 5 of Week 1)
- Maximum Observed Plasma Concentration (Cmax)(Days 1 and 5 of Week 1)
- Time to Maximum Plasma Concentration (Tmax) and Terminal Elimination Half-Life (t1/2)(Days 1 and 5 of Week 1)
- Plasma Concentration at Pre-dose (Cpre) and Plasma Concentration at End of Infusion (CT)(Days 1 and 5 of Week 1)
- Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) and Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24])(Days 1 and 5 of Week 1)
- Number of Participants With Adverse Events (AEs), Serious AEs, Treatment-Related AEs, Treatment-Related Serious AEs, AEs Leading to Death, Treatment-Related AEs Leading to Death, AEs of Grade 3 or 4 and Treatment-Related AEs of Grade 3 or 4(Time from first dose up to 28 days after last dose of study treatment, reported between day of first participant randomized, that is, Jun 2009 until cut-off date (07 Feb 2013))
- Mean Residence Time From Time 0 to Infinity (MRT [0-infinity])(Days 1 and 5 of Week 1)
- Plasma Clearance (CL)(Days 1 and 5 of Week 1)
- Apparent Volume of Distribution During the Terminal Phase (Vz) and Apparent Volume of Distribution at Steady State (Vss)(Days 1 and 5 of Week 1)
- Number of Participants With AEs Belonging to Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) Thromboembolic Events and Hemorrhage With NCI-CTC Toxicity Grade 3 or 4(Time from first dose up to 28 days after last dose of study treatment, reported between day of first participant randomized, that is, Jun 2009 until cut-off date (07 Feb 2013))
- Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) and Lab Parameters(Time from first dose up to 28 days after last dose of study treatment, reported between day of first participant randomized, that is, Jun 2009 until cut-off date (07 Feb 2013))
研究者
研究点 (2)
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