Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer Patients Undergoing Radiation Therapy Prior to the Resection of Locally Advanced Tumors, and Idiopathic Pulmonary Fibrosis Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Ability to detect increased collagen deposition in pulmonary fibrosis.
研究概览
简要总结
The goal of this study is to investigate the safety of [68Ga]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis.
详细描述
The investigators have developed [68Ga]CBP8, a gallium-68 labeled collagen binding PET imaging probe, which selectively binds collagen type I. Collagen deposition is a pivotal event in several human conditions including pulmonary fibrosis. The investigator's studies in mice showed that [68Ga]CBP8 binds collagen with high affinity and has excellent pharmacological and pharmacokinetic profiles with high target uptake and low retention in background tissues and organs. [68Ga]CBP8 was shown in a mouse model to be effective for detecting lung fibrosis. [68Ga]CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. In addition, [68Ga]CBP8 could be used to monitor response to treatment. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings.
The investigators thus aim to perform the first in human studies of [68Ga]CBP8:
- To evaluate the safety of [68Ga]CBP8 and its whole body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers.
- To establish the accuracy of [68Ga]CBP8-PET to detect radiation-induced fibrosis in lung cancer patients and correlate collagen-targeted [68Ga]CBP8-PET imaging with HRCT and histology in lung cancer patients.
- To determine whether collagen deposition as assessed by [68Ga]CBP8-PET molecular imaging can predict disease progression in IPF patients and patients with other types of ILD with a fibrotic component.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Total enrollment for all groups will not exceed 100 subjects.
- •Group 1: Healthy subjects
- •Age greater than 18 years
- •Be deemed healthy at screening visit as determined by the physician investigator or nurse practitioner, based on the following assessments at Screening: physical examination, medical history, and vital signs
- •Have the ability to give written informed consent;
- •No known history of pulmonary disease (excluding pulmonary nodules);
- •No prior history of tobacco use.
- •Group 2: Lung cancer subjects
- •Eligible patients will be those harboring locally advanced clinical stage IIIA NSCLC who are deemed candidates for multi-modality therapy, i.e. concurrent chemotherapy and radiation followed by pulmonary resection.
- •Age greater than 18 years
- •Have the ability to give written informed consent.
- •No tobacco use within the prior 6 months.
- •Group 3: Subjects with pulmonary fibrosis
- •IPF (with a UIP or probable UIP pattern); or other forms of interstitial lung disease (ILD), including CTD-ILD, with a fibrotic component as noted by the presence of reticular markings and / or traction bronchiectasis and / or honeycombing on CT;
- •Age: 40-80 years old;
- •Have the ability to give written informed consent;
- •No tobacco use within the prior 6 months
- •Group 4: Subjects with chronic lung allograft dysfunction (CLAD)
- •Status post lung transplantation
- •Clinical diagnosis of chronic lung allograft dysfunction
- •Age: 40-80 years old;
- •Have the ability to give written informed consent;
- •No tobacco use within the prior 6 months
- •Group 5: Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis
- •CT findings with ground glass opacities / consolidation or fibrotic changes with new onset during or within 3 months of receipt of ICI therapy
- •Age greater than 18 years
- •Have the ability to give written informed consent
- •No tobacco use within the prior 6 months
排除标准
- •Electrical implants such as cardiac pacemaker or perfusion pump;
- •Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing;
- •eGFR of less than 30 mL/min/1.73 m2 within the past 90 days for group 4 subjects; history of chronic kidney disease for subjects in groups 1-3 and 5;
- •Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
- •Claustrophobic reactions;
- •Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
- •Unable to lie comfortably on a bed inside the MR-PET;
- •BMI > 33 (limit of the MRI table);
- •Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures);
- •Known history of pulmonary disease (except for pulmonary fibrosis in the study group, ICI pneumonitis in the study group, or CLAD in the study group), recent pneumonia or respiratory tract infections within 6 weeks of enrollment, prior radiation therapy to the thorax (except for the lung cancer patients in aim 2);
- •Pneumonia or other acute respiratory illness within 6 weeks of study entry (except for pulmonary fibrosis), pneumonia defined with elevated WBC, fever, infiltrate on CXR and need for antibiotics
研究组 & 干预措施
Healthy Individuals
Healthy volunteers will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: [68Ga]CBP8 (Drug)
Healthy Individuals
Healthy volunteers will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: PET Imaging (Diagnostic Test)
Lung Cancer Subjects
Lung cancer patients will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: [68Ga]CBP8 (Drug)
Lung Cancer Subjects
Lung cancer patients will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: PET Imaging (Diagnostic Test)
Pulmonary Fibrosis Subjects
Idiopathic pulmonary fibrosis patients or patients with other types of interstitial lung disease with a fibrotic component will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: [68Ga]CBP8 (Drug)
Pulmonary Fibrosis Subjects
Idiopathic pulmonary fibrosis patients or patients with other types of interstitial lung disease with a fibrotic component will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: PET Imaging (Diagnostic Test)
Subjects with chronic lung allograft dysfunction (CLAD)
Subjects with chronic lung allograft dysfunction (CLAD) will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: [68Ga]CBP8 (Drug)
Subjects with chronic lung allograft dysfunction (CLAD)
Subjects with chronic lung allograft dysfunction (CLAD) will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: PET Imaging (Diagnostic Test)
Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis
Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: [68Ga]CBP8 (Drug)
Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis
Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis will receive [68Ga]CBP8 and undergo PET imaging.
干预措施: PET Imaging (Diagnostic Test)
结局指标
主要结局
Ability to detect increased collagen deposition in pulmonary fibrosis.
时间窗: Two hours
Probe lung uptake will be measured in pulmonary fibrosis subjects and compared to lung uptake in healthy volunteers. We expect greater uptake in the lungs of IPF patients and patients with other types of ILD with a fibrotic component.
次要结局
- Ability of the degree of collagen deposition to predict disease progression.(Up to 36 months)
研究者
Peter Caravan
Professor of Radiology
Massachusetts General Hospital