A Phase 1b, Randomized, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) and Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma (TARGET-I)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 4
- 主要终点
- Objective response rate (ORR) determined by MRI scan review
研究概览
简要总结
Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant primary brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase Ib study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified, conditionally replicative and oncolytic human-derived adenovirus. DNX-2401 is delivered directly into the tumor where it may establish an active infection by replicating in and killing tumor cells.
详细描述
Enrollment has been completed for the randomized portion of the study with ongoing evaluation of tumor response and safety. No additional subjects will be randomized or receive interferon gamma (IFN-γ).
The non-randomized portion of the study is open for screening and enrollment. Eligible subjects will receive a single intratumoral injection of DNX-2401 into a recurrent glioblastoma or gliosarcoma brain tumor using the Alcyone MEMS Cannula (AMC™) System (cannula). Tumor response and safety will be evaluated.
After receiving DNX-2401, subjects will return to the clinic for study visits at regular intervals for safety monitoring, MRI scans and other assessments for up to 18 months. Thereafter, they will be followed closely for safety and survival.
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
- •Glioblastoma or gliosarcoma in first or second recurrence only
- •Documented tumor recurrence or progression after failing prior surgical resection, chemotherapy, or radiation
- •Tumor size greater than or equal to 1.0 cm in two perpendicular diameters
- •Not undergoing surgical resection or for whom gross total resection is not possible
- •Karnofsky Performance Status greater than or equal to 70%
排除标准
- •Multiple intracranial malignant glioma lesions
- •Tumor location or involvement that would result in risk of ventricular penetration during tumor injection
- •Tumor involving both hemispheres or that which involves the subependyma or suspected cerebrospinal fluid dissemination
- •Tumor involving brain stem
- •Documented extracranial metastasis
- •Inability to undergo MRI
- •Pregnant or nursing females
- •Any medical condition that precludes the surgery necessary to administer DNX-2401 into the tumor using the cannula
- •Immunocompromised subjects or those with autoimmune conditions, active hepatitis or positive for human immunodeficiency virus (HIV)
- •Li-Fraumeni Syndrome
- •Other protocol-defined inclusion/exclusion criteria may apply as outlined in the relevant protocol version
研究组 & 干预措施
DNX-2401 alone
Single intratumoral injection of DNX-2401
干预措施: Single intratumoral injection of DNX-2401 (Drug)
DNX-2401 + Interferon gamma (IFN-γ)
Interferon gamma (IFN-γ) beginning at Day 14
干预措施: Single intratumoral injection of DNX-2401 (Drug)
DNX-2401 + Interferon gamma (IFN-γ)
Interferon gamma (IFN-γ) beginning at Day 14
干预措施: Interferon-gamma (Drug)
结局指标
主要结局
Objective response rate (ORR) determined by MRI scan review
时间窗: 1.5 years
Interval tumor size change will be measured
次要结局
- Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma(1.5 years)
- Changes in responses to quality of life questionnaires(1.5 years)
- Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings(1.5 years)
- Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment(1.5 years)
- Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).(1.5 years)