A Randomized Pivotal Study Assessing the Safety and Efficacy of Targeted Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound During the Standard of Care Treatment of Brain Metastases of Non-small Cell Lung Cancer (NSCLC) Origin
概览
- 阶段
- 3 期
- 干预措施
- Blood Brain Barrier Opening - Oncology
- 疾病 / 适应症
- 未指定
- 发起方
- InSightec
- 入组人数
- 30
- 试验地点
- 16
- 主要终点
- tumor lesion(s) on the MRI images
- 状态
- 招募中
- 最后更新
- 16天前
概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the treatment of NSCLC brain metastases in patients who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors.
详细描述
This is a prospective, multi-center, randomized, two-arm, controlled, pivotal clinical trial to evaluate the safety and efficacy of targeted blood brain barrier opening using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors for their primary disease. The study will be conducted at up to 30 centers in the US. The immunotherapy regimen (every 3 weeks for 6 cycles) of prescribed ICI therapy is per the FDA approved labeling and the subjects prescribed standard of care therapy for their primary NSCLC. The study aims to demonstrate superiority of Exablate BBBO targeted to their brain metastases over the standard of care without Exablate BBBO with respect to the percentage of subjects achieving Objective Response Rate (ORR) by 6 months follow-up.
研究者
入排标准
入选标准
- •Participant is ≥ 18 years of age
- •The participant provides written informed consent for the trial
- •Participant is willing to comply with all study procedures for the duration of the study
- •Participant has a Karnofsky Performance Status ≥ 70% and/or ECOG 0-2
- •Participant is a NSCLC subject prescribed immune checkpoint inhibitor systemic therapy according to on-label use with the target brain lesion(s) measuring ≥ 0.5 cm in longest diameter. Target mets may include: De novo mets for which surgery and radiation can be deferred, Mets with or without history of prior radiation, Mets with history of radiation after at least 8 weeks since last radiation treatment, and In the event a previously treated met has progressed according to institutional practice within 4 weeks post radiation treatment, the met may be study eligible, and/or if in the opinion of the Investigator, the subject may benefit from the study procedure.
- •Female subject is not planning pregnancy during the study duration and confirmed NOT PREGNANT each procedure day.
- •Screening/Baseline laboratory values Screening/Baseline should adhere to local standard of care lab values for ICI therapy
排除标准
- •Participant has evidence of acute intracranial hemorrhage
- •Participant at risk for spontaneous intracranial hemorrhage (e.g., history of metastatic melanoma or other tissue histology).
- •Participant has signs and symptoms of increased intracranial pressure or symptomatic mass effect, midline shift or evidence of subfalcine, uncal or tonsillar herniation.
- •Participant receiving Bevacizumab (Avastin) therapy, or other drugs with a proclivity for causing bleeding.
- •History of bleeding disorders or tissue pathologies which increase the subject's risk of hemorrhage for anticoagulation medications, implement pre-surgical standard procedure to avoid increased risk of a bleeding event.
- •Participant has an infectious viral infection such as active Hepatitis B, Hepatitis C or detectable HIV viral load or participants with active bacterial infection such as TB (Bacillus tuberculosis) that may, in the opinion of the investigator, interfere with the subject receiving the study therapy or procedures or otherwise impact their participation in the trial.
- •Subjects with evidence of cranial or systemic infection.
- •Participant has received a solid organ or hematopoietic stem cell transplant.
- •Participant has received a live vaccine within 28 days prior to the first on-study ICI infusion with or without Exablate.
- •Known sensitivity to DEFINITY® ultrasound contrast agent or hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol, as found in MiraLAX and bowel prep products.
研究组 & 干预措施
ICI Systemic Therapy with Exablate BBBO
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
干预措施: Blood Brain Barrier Opening - Oncology
ICI Systemic Therapy with Exablate BBBO
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
干预措施: Pembrolizumab
ICI Systemic Therapy with Exablate BBBO
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
干预措施: Iptilimumab
Control Arm (ICI Systemic Therapy on-label use only)
subjects will undergo planned on-label ICI Systemic Therapy.
干预措施: Iptilimumab
ICI Systemic Therapy with Exablate BBBO
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
干预措施: Atezolizumab
ICI Systemic Therapy with Exablate BBBO
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
干预措施: Cemiplimab
ICI Systemic Therapy with Exablate BBBO
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
干预措施: Nivolumab
Control Arm (ICI Systemic Therapy on-label use only)
subjects will undergo planned on-label ICI Systemic Therapy.
干预措施: Pembrolizumab
Control Arm (ICI Systemic Therapy on-label use only)
subjects will undergo planned on-label ICI Systemic Therapy.
干预措施: Atezolizumab
Control Arm (ICI Systemic Therapy on-label use only)
subjects will undergo planned on-label ICI Systemic Therapy.
干预措施: Cemiplimab
Control Arm (ICI Systemic Therapy on-label use only)
subjects will undergo planned on-label ICI Systemic Therapy.
干预措施: Nivolumab
结局指标
主要结局
tumor lesion(s) on the MRI images
时间窗: up to 6 months
Efficacy will be determined by the response of the tumor lesion(s) compared to baseline. Tumor lesions on the MRI images (units: mm) will be measured every three weeks up to six months.
Adverse events
时间窗: up to 6 months
Adverse events \[ Time Frame: Through study completion, up to 6 months\]. All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria.
次要结局
- evaluation of Neuro Oncology Brain Mets (RANO-BM) response(up to 6 months)
- Time to response for brain metastases by treatment arm [applicable to the completed stage 1a only](up to 6 months)