Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer, and Idiopathic Pulmonary Fibrosis Patients

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

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

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Fibrosis; Lung Cancer
• Intervention / Treatment: Drug: [68Ga]CBP8; Diagnostic test: PET Imaging

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sydney B Montesi, MD; Phone Number: 617 724 4030; Email: sbmontesi@partners.org
• Study Contact Backup: Name: Layla Rahimi; Phone Number: 617 724 5548; Email: Layla.Rahimi@MGH.HARVARD.EDU

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Sydney Montesi, MD
      • Principal Investigator: Sydney Montesi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

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;
• 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), 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Individuals; Healthy volunteers will receive [68Ga]CBP8 and undergo PET imaging.	Drug: [68Ga]CBP8; Up to 15 mCi of [68Ga]CBP8 will be administered to each subject.; Diagnostic test: PET Imaging; All subjects will undergo PET imaging after administration of [68Ga]CBP8.
Experimental: Lung Cancer Subjects; Lung cancer patients will receive [68Ga]CBP8 and undergo PET imaging.	Drug: [68Ga]CBP8; Up to 15 mCi of [68Ga]CBP8 will be administered to each subject.; Diagnostic test: PET Imaging; All subjects will undergo PET imaging after administration of [68Ga]CBP8.
Experimental: 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.	Drug: [68Ga]CBP8; Up to 15 mCi of [68Ga]CBP8 will be administered to each subject.; Diagnostic test: PET Imaging; All subjects will undergo PET imaging after administration of [68Ga]CBP8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to detect increased collagen deposition in pulmonary fibrosis.	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.	Two hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of the degree of collagen deposition to predict disease progression.	Probe lung uptake in pulmonary fibrosis patients will be correlated with change in forced vital capacity over the prior 12 months and prospectively over the following 12-36 months.	Up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury.	Probe lung uptake will be measured in lung cancer patients prior to surgical resection and compared to histologic measures of fibrosis.	Up to 3 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Sydney B Montesi, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: PET Imaging; Molecular Imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases, Interstitial; Fibrosis; Lung Neoplasms; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: 2017P002718; R01HL131907 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No