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

NCT ID: NCT03535545

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2026-06-30

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.

Conditions

Pulmonary Fibrosis; Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Subjects with chronic lung allograft dysfunction (CLAD)

Subjects with chronic lung allograft dysfunction (CLAD) will receive \[68Ga\]CBP8 and undergo PET imaging.

Group Type: EXPERIMENTAL

[68Ga]CBP8

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

PET Imaging

Intervention Type: DIAGNOSTIC_TEST

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis

Subjects with immune-checkpoint-inhibitor (ICI) pneumonitis will receive \[68Ga\]CBP8 and undergo PET imaging.

Group Type: EXPERIMENTAL

[68Ga]CBP8

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

PET Imaging

Intervention Type: DIAGNOSTIC_TEST

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

Healthy Individuals

Healthy volunteers will receive \[68Ga\]CBP8 and undergo PET imaging.

Group Type: EXPERIMENTAL

[68Ga]CBP8

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

PET Imaging

Intervention Type: DIAGNOSTIC_TEST

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

Lung Cancer Subjects

Lung cancer patients will receive \[68Ga\]CBP8 and undergo PET imaging.

Group Type: EXPERIMENTAL

[68Ga]CBP8

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

PET Imaging

Intervention Type: DIAGNOSTIC_TEST

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

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.

Group Type: EXPERIMENTAL

[68Ga]CBP8

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

PET Imaging

Intervention Type: DIAGNOSTIC_TEST

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

Interventions

[68Ga]CBP8

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

Intervention Type: DRUG

PET Imaging

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Peter Caravan

Professor of Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sydney B Montesi, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sydney B Montesi, MD

Role: CONTACT

sbmontesi@partners.org

617 724 4030

Abimbola Akinniyi

Role: CONTACT

aakinniyi@mgb.org

781 513 0207

Facility Contacts

Sydney Montesi, MD

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 28381537 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28611243 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31161770 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37116909 (View on PubMed)

Abston E, Zhou IY, Saenger JA, Shuvaev S, Akam E, Esfahani SA, Hariri LP, Rotile NJ, Crowley E, Montesi SB, Humblet V, Arabasz G, Catana C, Fintelmann FJ, Caravan P, Lanuti M. Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe. medRxiv [Preprint]. 2023 Sep 26:2023.09.25.23295897. doi: 10.1101/2023.09.25.23295897.

Reference Type: DERIVED

PMID: 37808864 (View on PubMed)

Other Identifiers

R01HL153606

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017P002718

Identifier Type: -

Identifier Source: org_study_id