Clinical trial NCT03535545: Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer, and Idiopathic Pulmonary Fibrosis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pulmonary Fibrosis
Lung Cancer
Keywords: PET Imaging
Molecular Imaging
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-05-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Healthy control subjects will be enrolled first and then subjects with lung cancer and idiopathic pulmonary fibrosis and other types of interstitial lung disease or other types of lung disease with a fibrotic component meeting inclusion criteria.
Primary purpose: DIAGNOSTIC

Brief summary: The goal of this study is to investigate the safety of \[68Ga\]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis.

Detailed description: 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:

1. To evaluate the safety of \[68Ga\]CBP8 and its whole body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers.
2. 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.
3. 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.

Eligibility criteria: Inclusion Criteria: 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Ability to detect increased collagen deposition in pulmonary fibrosis.
timeFrame: Two hours
Secondary outcomes:
measure: Ability of the degree of collagen deposition to predict disease progression.
timeFrame: Up to 36 months
Other outcomes:
measure: Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury.
timeFrame: Up to 3 months
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Sydney B Montesi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.
citation: Desogere P, Tapias LF, Rietz TA, Rotile N, Blasi F, Day H, Elliott J, Fuchs BC, Lanuti M, Caravan P. Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. J Nucl Med. 2017 Dec;58(12):1991-1996. doi: 10.2967/jnumed.117.193532. Epub 2017 Jun 13.
citation: Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.
citation: Izquierdo-Garcia D, Desogere P, Fur ML, Shuvaev S, Zhou IY, Ramsay I, Lanuti M, Catalano OA, Catana C, Caravan P, Montesi SB. Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. J Nucl Med. 2023 May;64(5):775-781. doi: 10.2967/jnumed.122.264530. Epub 2022 Dec 8.