A Phase 2 Study of MEDI-575 in Adult Subjects With Recurrent Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Progression-free Survival Rate at 6 Months
研究概览
简要总结
The primary objective of this Phase II study is to evaluate the progression-free survival at 6 months in adult subjects with a first recurrence of Glioblastoma Multiforme who are treated with MEDI-575.
详细描述
This is a Phase 2, multicenter, open-label, single-arm study to evaluate the antitumor activity, safety, and pharmacology of MEDI-575 in adult subjects with first recurrence of GBM.
Approximately 55 subjects will be enrolled to determine the preliminary efficacy profile of MEDI-575 in the treatment of subjects with first recurrence of GBM. Subjects will receive MEDI-575 as a 60-minute IV infusion on Day 1 every 21 days until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, or other reasons for subject withdrawal.
The primary assessment of antitumor activity is PFS-6; tumor response and progression will be determined using Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group v.1. Approximately 15 investigational sites in the United States will participate in this study. All subjects will be followed every 3 months for the duration of the trial (defined as 9 months from the date the last subject is entered into the trial or when the sponsor stops the study.
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 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent and HIPAA authorization (applies to covered entities in the USA only) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
- •Age ≥18 years old at the time of screening
- •Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma)
- •Previous first line treatment with radiotherapy and temozolomide (treatment prior to radiation and temozolomide permitted, [ie, Gliadel])
- •Documented first recurrence of GBM by diagnostic biopsy or by contrast-enhanced magnetic resonance imaging (MRI) as per Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (Wen et al, 2010)
- •Life expectancy ≥ 12 weeks
- •Adequate hematologic and organ function
- •Negative serum pregnancy test (women only)
- •Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential
排除标准
- •Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, hormonal therapy or investigational agent 30 days prior to study entry
- •Concurrent enrollment in another clinical study involving an investigational agent
- •Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
- •Previous mAb treatment specifically directed against PDGF or PDGF receptors
- •Previous bevacizumab or other VEGF and anti-angiogenic treatment
- •More than 1 recurrence of GBM
- •Any surgery (not including minor diagnostic procedures) within 2 weeks prior to baseline disease assessments; or not fully recovered from any side effects of previous procedures
- •History of serious allergy or reaction to any component of the MEDI-575 formulation
- •New York Heart Association ≥ Grade 2 congestive heart failure within 6 months prior to study entry
- •Uncontrolled or significant cardiovascular disease
- •History of other invasive malignancy within 5 years prior to study entry except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
- •History of active human immunodeficiency virus or active hepatitis B or C viral infection will be excluded to eliminate the risk of increased AEs due to immune compromise.
- •Systemic immunosuppressive therapy.
- •Subjects taking corticosteroids must be on a stable dose for 7 days prior to initiation of treatment with MEDI-575 16) Presence of extracranial metastatic or leptomeningeal disease
研究组 & 干预措施
MEDI-575, 25 mg/kg
MEDI-575 administered as an intravenous infusion at 25 mg/kg over a period of 60-minutes on Day 1 of each 21-day cycle until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, or other reasons for participants withdrawal.
干预措施: MEDI-575 (Drug)
结局指标
主要结局
Progression-free Survival Rate at 6 Months
时间窗: 6 months
Progression-free survival (PFS) rate at 6 months is defined as the proportion of participants who neither progressed nor died before 6 months after the first dose. Progression was determined using Updated Response Assessment Criteria of High Grade Gliomas: Response Assessment in Neuro-Oncology Working Group (RANO criteria). Progression was defined as at least 25% increase in measurement of enhancing lesions compared with the smallest tumor measurement obtained during the study; or significant increase in T2/fluid attenuated inversion recovery (FLAIR) nonenhancing lesion compared with baseline scan or best response; or any new lesion; or clear clinical deterioration; or failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease. PFS-6 was estimated using Kaplan-Meier method.
次要结局
- Percentage of Participants With Objective Response(Study entry through the end of the study, up to 21 months)
- Time to Response
- Time to Progression(Study entry until the first documented disease progression, up to 16 months)
- Progression-free Survival Rate at 3 Months and 9 Months(3 months and 9 months)
- Percentage of Participants With Expression of PDGFR Alpha in the Tumor Samples(Screening (Day-28 to Day -1))
- Treatment-emergent Adverse Events Related to Laboratory Parameters(Baseline to last record on study, up to 21 months)
- Duration of Response
- Number of Participants With Worst ECOG Performance Status On-study and Last Record On-study(Baseline to last record on study, up to 21 months)
- Percentage of Participants With Best Overall Response(Study entry through the end of the study, up to 21 months)
- Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations(Baseline to last record on study, up to 21 months)
- Treatment-emergent Adverse Events Related to Vital Sign Parameters(Baseline to last record on study, up to 21 months)
- Progression-free Survival(9 months)
- Overall Survival(Study entry to death, up to 16 months)
- Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events(Baseline to last record on study, up to 21 months)