A Phase 0, First in Human, Open-label Study of Intravenous Aminolevulinic Acid HCl (ALA) and MR-Guided Focused Ultrasound Device (MRgFUS) in Participants With Recurrent High Grade Glioma (HGG)
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Biological changes associated with the sonodynamic therapy
研究概览
简要总结
A Phase 0 single center, first in human, open-label study of ascending energy doses of sonodynamic therapy (SDT) utilizing the MRgFUS combined with intravenous ALA to assess safety and efficacy in up to 45 participants with recurrent HGG. Eligible participants who are scheduled for resection will be administered intravenous (IV) aminolevulinic acid HCl (ALA) approximately six to seven (6-7) hours prior to receiving sonodynamic therapy (SDT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Arms A-D: Prior resection of histologically diagnosed high-grade gliomas (III and IV) defined as participants who have progressed on or following standard therapy as determined by the investigator. Arm E: Participant at first recurrence with an unmethylated HGG, has completed standard therapy and is not currently scheduled for resection.
- •Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI with positive perfusion.
- •Arms A-D (only): Have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with a volume of at least 6 cm3 and ≤ 20cm3 of targeted treatment area.
- •Age ≥18 at time of consent.
- •Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982).
- •Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility)
- •Adequate bone marrow function:
- •absolute neutrophil count ≥1,000/mcL
- •Platelets (at time of surgery) ≥100,000/mcL
- •hemoglobin ≥8.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator.
- •Adequate hepatic and renal function:
- •total bilirubin ≤1.5 X ULN. Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
- •AST(SGOT) ≤3 X institutional ULN
- •ALT(SGPT) ≤3 X institutional ULN
- •GGT ≤3 X institutional ULN
- •Serum creatinine ≤1.5 X institutional ULN
- •Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant has had a hysterectomy.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 3 months after the end of treatment administration.
- •For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 1 month after the end of treatment administration. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid.
- •Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day
- •A washout period of at least 14 days is required between last chemotherapy dose and Day 1 (provided the patient did not receive radiotherapy).
- •Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and Day
- •Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
- •Has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
- •Willingness and ability to comply with scheduled visits, treatment plans, Lifestyle Considerations, laboratory tests and other procedures.
排除标准
- •Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
- •Have had a recent (≤3 months prior to first dose of study drug) transient ischemic attack or stroke.
- •Significant vascular disease (e.g. aortic aneurysm)
- •Evidence of bleeding diathesis or coagulopathy
- •Diagnosis of porphyria
- •Unstable angina and/or congestive heart failure within the last 6 months
- •Transmural myocardial infarction within the last 6 months
- •Serious and inadequately controlled cardiac arrhythmia
- •Acute exacerbation of chronic obstructive pulmonary disease
- •Inability to undergo MRI (e.g., presence of a pacemaker)
- •Pregnancy or breastfeeding
- •Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
- •Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
- •Hypersensitivity against porphyrins
- •Treatment with another investigational drug within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
- •Has an Overall Skull Density Ratio of 0.45 (±0.05) or less as calculated from the screening CT.
研究组 & 干预措施
Arm C ALA Dose-escalation
In Arm C, the MRgFUS power/energy dose will be fixed based on Arm A MTD/OBD, with the SONALA-001 dose escalation.
干预措施: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS) (Combination Product)
Arm A Energy Dose-escalation
In Arm A, the dose-escalation cohort, there will be 3 cohorts of ascending MRgFUS power/energy dose combinations with a fixed SONALA-001 dose and fixed surgical time. Arm A will determine the power/energy dose combination for Arm B.
干预措施: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS) (Combination Product)
Arm B Time-escalation
In Arm B, the time-escalation cohort, the SONALA-001 and power/energy dose combination will be fixed. Participants will be enrolled into two time cohorts (2 days and 6 days post-SDT).
干预措施: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS) (Combination Product)
Arm D MRgFUS alone
In Arm D, MRgFUS treatment alone will be given at the optimal energy determined from previous Arms.
干预措施: MR-Guided Focused Ultrasound device (MRgFUS) (Device)
Arm E Optimal energy and ALA dose
In Arm E patients will receive treatment at the optimal energy and ALA dose determined form prior Arms.
干预措施: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS) (Combination Product)
结局指标
主要结局
Biological changes associated with the sonodynamic therapy
时间窗: Intraoperatively 4, 7, or 14 days post sonodynamic therapy
The percentage (%) of Cleaved Caspase-3 of the surgical tissue will be quantified and compared to intra-patient control specimens.
Radiographic evidence of tumor physiological imaging changes associated with SDT in recurrent HGG patients (Arm E)
时间窗: Intraoperatively 4, 7, or 14 days post sonodynamic therapy
Volume of enhancing tumor will quantified and compared between pre and post procedural scans (Arm E)
次要结局
- Progression-free survival(6 months)
- Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy(Pre and 14 Days Post-operative scan)
- To identify oxidative stress in tissue exposed to sonodynamic therapy in recurrent high-grade glioma patients.(Intraoperatively 2, 4, or 6 days post sonodynamic therapy)
- To characterize the biological changes associated with sonodynamic therapy in recurrent high-grade glioma patients.(Intraoperatively 4, 7, or 14 days post sonodynamic therapy)
- Overall Survival(24 months)
- Best Overall Response (BOR)(24 months)
- Performance of MRgFUS(Day 1)
- Safety and Tolerability(up to 30 days after the last study dose)
研究者
Nader Sanai
Deputy Director, Ivy Brain Tumor Center
St. Joseph's Hospital and Medical Center, Phoenix