Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
This phase I trial studies the side effects and best dose of carcinoembryonic antigen-expressing measles virus (MV-CEA) in treating patients with glioblastoma multiforme that has come back. A virus, called MV-CEA, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and toxicity of intratumoral and resection cavity administration of an Edmonston's strain measles virus genetically engineered to produce CEA (MV-CEA) in patients with recurrent glioblastoma multiforme.
II. To determine the maximum tolerated dose (MTD) of MV-CEA. III. To characterize viral gene expression at each dose level as manifested by CEA titers.
IV. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration.
V. To assess humoral and cellular immune response to the injected virus. VI. To assess in a preliminary fashion antitumor efficacy of this approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed glioma with histologic confirmation at initial diagnosis or recurrence
- •Candidate for gross total or subtotal resection
- •Absolute neutrophil count (ANC) >= 1500/uL
- •Platelets (PLT) >= 100,000/uL
- •Total bilirubin =< 1.5 x upper normal limit (ULN)
- •Aspartate aminotransferase (AST) =< 2 x ULN
- •Creatinine =< 2.0 x ULN
- •Hemoglobin (Hgb) >= 9.0 gm/dL
- •Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.3 x ULN
- •Ability to provide informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay
- •Normal serum CEA levels (< 3 ng/ml) at the time of registration
- •Willing to provide biologic specimens as required by the protocol
- •Negative serum pregnancy test done =< 7 days prior to registration (for women of childbearing potential only)
排除标准
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Active infection =< 5 days prior to registration
- •History of tuberculosis or history of purified protein derivative (PPD) positivity
- •Any of the following therapies:
- •Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based chemotherapy)
- •Immunotherapy =< 4 weeks prior to registration
- •Biologic therapy =< 4 weeks prior to registration
- •Bevacizumab =< 12 weeks prior to registration
- •Non-cytotoxic antitumor drugs, i.e., small molecule cell cycle inhibitors =< 2 weeks prior to registration
- •Radiation therapy =< 6 weeks prior to registration
- •Any viral or gene therapy prior to registration
- •Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
- •New York Heart Association classification III or IV
- •Requiring blood product support
- •Inadequate seizure control
- •Expected communication between ventricles and resection cavity as a result of surgery
- •Human immunodeficiency virus (HIV)-positive test result, or history of other immunodeficiency
- •History of organ transplantation
- •History of chronic hepatitis B or C
- •Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
- •Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
- •Allergy to measles vaccine or history of severe reaction to prior measles vaccination
研究组 & 干预措施
Arm A (resection cavity administration)
Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (resection cavity administration)
Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm B (intratumoral and resection cavity administration)
Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by MV-CEA IT through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (intratumoral and resection cavity administration)
Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by MV-CEA IT through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm A (resection cavity administration)
Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity.
干预措施: Carcinoembryonic Antigen-Expressing Measles Virus (Biological)
Arm B (intratumoral and resection cavity administration)
Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by MV-CEA IT through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed.
干预措施: Carcinoembryonic Antigen-Expressing Measles Virus (Biological)
结局指标
主要结局
Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities
时间窗: 2 weeks
The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include hematologic events grade 3 or higher (except grade 3 ANC lasting \< 72 hours), non-hematologic events graded 3 or higher (except grade 3 nausea, vomiting, or diarrhea were to be considered DLT only if patient was receiving the max supportive care and alopecia was not considered dose limiting), neurologic toxicity grade 2 or higher, grade 2 allergic reactions asymptomatic bronchospasm and/or urticarial, grade 3 or higher allergic reactions, viremia lasting for 6 weeks or more from last viral administration deemed at least possibly related to treatment. The number of patients reporting a dose-limiting event are reported.
Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0
时间窗: Up to 2 weeks
The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population.
次要结局
- Progression-free Survival (PFS)(Length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up, assessed up to 6 months)
- Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence(Up to 2 weeks)
- Survival(Up to 13 years)