NCT00805376已完成1 期
Phase I Trial of Conditionally Replication-Competent Adenovirus (DNX-2401, Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) DNX-2401
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of DNX-2401 that can be injected directly into brain tumors and into the surrounding brain tissue where tumor cells can multiply. A second goal is to study how the new drug DNX-2401 affects brain tumor cells and the body in general.
详细描述
The Study Drug:
DNX-2401 (formerly known as Delta-24-RGD-4C) is a virus that works by killing brain tumor cells. It is made from a common cold virus, called adenovirus, type 5. This virus normally causes the common cold, and most people around the world have been exposed many times to this common, naturally-occurring virus during their lives. Two (2) changes have been made to the adenovirus to make DNX-2401. The first change was to make the virus only grow in cancer cells. The second change was made to allow DNX-2401 to enter cancer cells more easily. These changes make DNX-2401 more able to multiply and kill cancer cells and less likely to multiply in normal cells.
Study Groups:
Participants will eventually be divided into 2 groups (Groups A and B).
At first, all participants will only be enrolled into Group A. Participants in Group A will receive the study drug but will not have the recurrent malignant glioma tumor removed by surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically proven recurrent malignant primary glioma will be eligible. Glioma type will be restricted to: GBM, gliosarcoma (GS), anaplastic gliomas [anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic infiltrating glioma (AIG), mixed anaplastic glioma (MAG), anaplastic ependymoma]
- •Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan within 15 days prior to Day 0/Baseline procedure after failing prior surgical resection, biopsy, chemotherapy or radiation
- •For patients entered in Group A (see Treatment Plan) tumors must be accessible for stereotactic injection. Tumors must be between 1.0 - 5.0 cm in diameter
- •For patients entered in Group B (see Treatment Plan) tumors must be surgically resectable, and surgical resection must be indicated at the time of baseline evaluation. Tumors must be >1.0 cm in diameter.
- •Patients will consent to have a biopsy taken at the time of the stereotactic injection to confirm the presence of malignant glioma (based on frozen section) before injection of DNX-2401
- •For each patient there must be a consensus between the physician investigators in this study that injection will not deliver DNX-2401 into the ventricular system. Patients must have a stable steroid regimen for at least 1 week prior to DNX-2401 administration
- •Patients may or may not have had prior chemotherapy
- •Patients must be willing and able to give informed consent
- •Age > /= 18 years
- •Patients must have a Karnofsky performance status greater than or equal to 70
- •Patients must have recovered from the toxic effects of prior therapy (i.e., CTC grade 1 or less). For example, they must be at least two weeks after vincristine, 6 weeks after nitrosoureas, and 3 weeks after procarbazine or temozolomide administration
- •Patients must have adequate bone marrow function (absolute granulocyte count > 1,500 and platelet count of > 100,000), adequate liver function (SGPT and alkaline phosphatase < 2 times institutional normals and bilirubin <1.5 mg%), and adequate renal function (BUN or creatinine <1.5 times institutional normal) prior to starting therapy
- •This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender
- •No exclusion to this study will be based on race. Minorities will actively be recruited to participate. The malignant glioma patient population treated at MDACC over the past year is as follows: American Indian or Alaskan Native - 0, Asian or Pacific Islander - <2%, Black, not of Hispanic Origin - 3%, Hispanic - 6%, White, not of Hispanic Origin - 88%, Other or Unknown - 2%, Total - 100%
排除标准
- •Any radiotherapy within 4 weeks prior to date of DNX-2401 administration.
- •Active uncontrolled infection or severe intercurrent medical conditions. All patients must be afebrile at baseline (i.e., < 38.0 Celsius [C])
- •Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. If the medication can be discontinued , based on the clinical judgment of the surgeon, prior to DNX-2401 injection then patient may be eligible.
- •History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems
- •Female who is pregnant and/or nursing. Because of the potential risk of a recombinant virus containing a gene involved in cellular growth regulation and differentiation which could potentially affect a developing fetus or growing infant, females who are pregnant, at risk of pregnancy, or breast feeding a baby during the study period are excluded
- •Tumor position that, in the Investigator's opinion, would pose the risk of penetration of the cerebral ventricular system during injection with study drug. If, during the DNX-2401injection procedure, penetration of the ventricular system is suspected or confirmed, DNX-2401 administration will be aborted
- •Immunocompromised subjects, subjects with autoimmune conditions, active hepatitis (B or C) or HIV seropositivity
- •Patients with Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways
- •Multiple intracranial malignant glioma lesions at the time of recurrence. Multiple enhancing areas within a single tumor will not be considered multiple glioma lesions
- •Tumor involvement which would require ventricular, brainstem or posterior fossa injection or access through a ventricle in order to deliver the virus
- •Tumor involving the subependyma or suspected cerebrospinal fluid (CSF) dissemination
- •Documented extracranial metastasis
- •Biologic/immunotherapy (e.g., IL-2, IL-12, interferon) within 4 weeks of DNX-2401 administration
- •Concurrent chemotherapy, radiation or biological therapy
- •Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc.
- •White blood cell (WBC) < 2.5 x 103/mm3, absolute neutrophil count (ANC) < 1.5 x 103/mm3, platelet < 100,000/mm3, hemoglobin (Hgb) < 10.0 gm/dL, prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) > 1.8 x control
- •Grade 4 hematological toxicity
- •Serum creatinine > 1.5 mg/dL
- •Liver transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) or total bilirubin > 2x the upper limits of normal
- •Vaccinations of any kind within 30 days prior to Delta-24-RGD-4C administration
- •Current diagnosis of other cancer except curative cervical cancer in situ, basal or squamous cell carcinoma of the skin. Patients with a history of another cancer, but who are cancer free for a minimum of three years remain eligible
- •History of encephalitis, multiple sclerosis, other CNS infection or primary CNS disease that would interfere with subject evaluation
- •Patients with history of prior gene transfer therapy or prior therapy with cytolytic virus of any type, especially DNX-2401
- •Males or females who refuse to use a double-barrier form of birth control during the study and for up to 6 months after injection with DNX-2401
研究组 & 干预措施
Group A: DNX-2401
Experimental
Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.
干预措施: DNX-2401 (Drug)
Group B: DNX-2401 + Surgery
Experimental
DNX-2401 injection + Tumor removal
干预措施: DNX-2401 (Drug)
Group B: DNX-2401 + Surgery
Experimental
DNX-2401 injection + Tumor removal
干预措施: Tumor Removal (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD) DNX-2401
时间窗: Assessed during 14 day waiting period between doses (every 28 days).
Each cohort of three subjects each sequentially assigned to escalating doses of DNX-2401, with acceptable grade of neurotoxicity Common Toxicity Criteria (CTC) \< grade 3, related to the study drug, and according to standard Gehan phase I dose-escalating criteria for toxicity.
次要结局
未报告次要终点
研究者
研究点 (1)
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