A Multicenter Phase 1 Study to Determine the Safety and Efficacy of Multiple Doses at Defined Intervals of Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL) Administered Via Intraventricular Catheter for Any Primary Solid Tumor Cancer With Leptomeningeal Metastases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
This is an open-label, multicenter, Phase 1 study to determine the safety and efficacy of multiple doses at defined intervals of rhenium (186Re) obisbemeda (rhenium-186 nanoliposome, 186RNL) administered via intraventricular catheter for any primary solid tumor cancer with leptomeningeal metastases to identify an MTD/MFD for a given dose, interval duration, and number of doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •At least 18 years of age.
- •Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
- •Documented LM from any primary solid tumor cancer per EANO-ESMO Clinical Practice Guidelines (Types I or IIA-C).
- •Karnofsky performance status of 70 to
- •Acceptable liver function:
- •Bilirubin ≤ 1.5 times the upper limit of normal.
- •AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal for subjects with normal liver.
- •AST (SGOT) and ALT (SGPT) ≤ 5.0 times the upper limit of normal for subjects with liver metastasis.
- •Acceptable renal function:
- •a. Creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation).
- •Acceptable hematologic functioning (without hematologic support):
- •ANC ≥ 1000 cells μL.
- •Platelet count ≥ 75,000/μL.
- •Hemoglobin ≥ 9.0 g/dL.
- •All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
- •Normal CSF flow and distribution by an accepted CSF flow study (e.g., 111Indium-DTPA or acceptable substitute) before first treatment with the study drug, based on study imaging interpretation and clinical correlation.
- •Corticosteroids are permitted as clinically indicated.
排除标准
- •The subject has not recovered to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study, at time of study registration.
- •a. Prior AEs due to alopecia, anemia, neutropenia, and lymphopenia are not required to be recovered to Grade ≤1 prior to study registration, assuming other inclusion criteria are satisfied.
- •Contraindications to the placement of an intraventricular catheter (i.e., Ommaya reservoir.)
- •Presence of or need for a Ventriculo-peritoneal or ventriculo-atrial shunt.
- •Females of childbearing potential who are pregnant, breastfeeding, or may possibly be pregnant, without a negative serum pregnancy test (see inclusion criteria).
- •Serious intercurrent illnesses, which could interfere with the planned treatment schedule.
- •Patients who had any therapeutic radiation dose to the whole brain regardless of when the radiation treatment was delivered, except:
- •Prior radiation dose to the spinal cord and/or cauda equina is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been > 14 days and ≤ 6 months, or was ≤45 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been > 6 months.
- •Prior stereotactic radiosurgery (SRS) to the brain or partial brain radiotherapy is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been > 14 days and ≤ 6 months, or was ≤ 45 Gy to the brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been > 6 months.
- •Prior or concurrent therapy:
- •a. Intrathecally delivered therapy: i. Concurrent: Concurrent intrathecal therapy. ii. Prior: Intrathecal therapy given less than 14 days before study registration.
- •b. Systemically delivered therapy: i. Concurrent: Systemically delivered therapy UNLESS LM develops while on systemically delivered therapy AND the systemically delivered therapy is NOT associated with more than grade 1 myelosuppression.
- •ii. Prior: Systemically delivered therapy given less than 28 days before study registration.
- •Projected survival of less than 60 days.
研究组 & 干预措施
Experimental: Multiple Doses
This is an open-label, multicenter, Phase 1 study to determine the safety and efficacy of multiple doses at defined intervals of rhenium (186Re) obisbemeda (rhenium-186 nanoliposome, 186RNL) administered via intraventricular catheter for any primary solid tumor cancer with leptomeningeal metastases to identify an MTD/MFD for a given dose, interval duration, and number of doses.
干预措施: 186RNL (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: 13 months
Evaluation of any toxicity associated with research treatment per Common Criteria for Adverse Events.
Safety and tolerability of multiple dose treatment
时间窗: 13 months
Evaluation of any toxicity associated with research treatment as determined by National Cancer Institute (NCI) common Terminology Criteria for adverse events (CTCAE).
Dose Distribution of 186RNL
时间窗: 13 months
SPECT imaging of the radioactive materials spread in the Cerebrospinal Fluid.
Maximum Tolerated Dose
时间窗: 13 months
Evaluation of any toxicity associated with research treatment per Common Criteria for Adverse Events.
Safety and tolerability of multiple dose treatment
时间窗: 13 months
Evaluation of any toxicity associated with research treatment as determined by National Cancer Institute (NCI) common Terminology Criteria for adverse events (CTCAE).
次要结局
- Evaluate Neurologic status by NANO scale(13 months)
- Determine the objective response rate (ORR).(13 months)
- Determine the overall survival (OS).(13 months)
- Characterize the dosimetry profile of 186RNL.(13 months)
- Determine neurologic progression-free survival (PFS).(13 months)
- Evaluate Neurologic status by NANO scale(13 months)