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

• ClinicalTrials.gov Identifier: NCT03535545
• Recruitment Status: Recruiting
• First Posted: May 24, 2018
• Last Update Posted: December 5, 2023
• Sponsor: Massachusetts General Hospital
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Peter Caravan, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Fibrosis; Lung Cancer	Drug: [68Ga]CBP8; Diagnostic Test: PET Imaging	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Healthy control subjects will be enrolled first and then subjects with lung cancer and idiopathic pulmonary fibrosis or other types of interstitial lung disease with a fibrotic component meeting inclusion criteria.
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• 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
• Actual Study Start Date: August 1, 2018
• Estimated Primary Completion Date: June 30, 2026
• Estimated Study Completion Date: June 30, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Ability to detect increased collagen deposition in pulmonary fibrosis. [ Time Frame: 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.

Secondary Outcome Measures :

1. Ability of the degree of collagen deposition to predict disease progression. [ Time Frame: Up to 36 months ]
   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.

Other Outcome Measures:

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

Eligibility Criteria

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

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

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

Contacts and Locations

Contacts

Contact: Sydney B Montesi, MD; 617 724 4030; sbmontesi@partners.org

Contact: Layla Rahimi; 617 724 5548; Layla.Rahimi@MGH.HARVARD.EDU

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Sydney Montesi, MD

Principal Investigator: Sydney Montesi, MD

Sponsors and Collaborators

Massachusetts General Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Sydney B Montesi, MD; Massachusetts General Hospital

More Information

Publications of Results:

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.

Other Publications:

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.

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.

• Responsible Party: Peter Caravan, Professor of Radiology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03535545
• Other Study ID Numbers: 2017P002718; R01HL131907 ( U.S. NIH Grant/Contract )
• First Posted: May 24, 2018
• Last Update Posted: December 5, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peter Caravan, Massachusetts General Hospital:

PET Imaging; Molecular Imaging

Additional relevant MeSH terms:

Lung Neoplasms; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Lung Diseases, Interstitial