Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury

• ClinicalTrials.gov Identifier: NCT04485286
• Recruitment Status: Recruiting
• First Posted: July 24, 2020
• Last Update Posted: May 3, 2023
• Sponsor: Massachusetts General Hospital
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Peter Caravan, Massachusetts General Hospital

Tracking Information

• First Submitted Date: July 21, 2020
• First Posted Date: July 24, 2020
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: July 19, 2020
• Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2021)

Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury. [ Time Frame: 3-6 Months ]

Probe uptake will be measured in lung cancer or pancreatic cancer patients 1) prior to radiation therapy and 2) 3-6 months after radiation therapy. We expect [68Ga]CBP8 signal to be increased in post radiation measurements over pre-radiation measurements in areas of irradiated tissue. Furthermore we expect that these areas will go on to develop radiation fibrosis.

Original Primary Outcome Measures (submitted: July 21, 2020)

Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury. [ Time Frame: 3-6 Months ]

Probe uptake will be measured in lung cancer patients 1) prior to radiation therapy and 2) 3-6 months after radiation therapy. We expect [68Ga]CBP8 signal to be increased in post radiation measurements over pre-radiation measurements in areas of irradiated lung. Furthermore we expect that these areas will go on to develop radiation fibrosis.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury
• Official Title: Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury
• Brief Summary: The goal of this study is to investigate the efficacy of [68Ga]CBP8 to detect collagen deposition in radiation induced tissue injury.

Detailed Description

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 radiation induced lung injury and in response to radiation therapy in pancreatic cancer. The investigator's studies in murine models of lung injury including radiation induced lung injury 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 idiopathic pulmonary fibrosis (IPF) supported the animal findings.

The investigators have conducted preliminary studies in humans with IPF and demonstrated a significant increase in [68Ga]CBP8 signal in subjects with IPF vs healthy controls.

The investigators thus aim to evaluate [68Ga]CBP8 in human subjects with radiation induced lung injury and in patients undergoing radiation therapy for pancreatic cancer:

To establish the ability of [68Ga]CBP8-PET to detect radiation-induced fibrosis in lung or pancreatic cancer patients through the course of disease development with repeated measures, and correlate signal with standard measures of radiation induced tissue injury such as HRCT or MRI.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Eligible subjects planning on receiving radiation for lung cancer or pancreatic cancer will be enrolled to undergo imaging with the PET Probe [68Ga]CBP8.

Masking: None (Open Label)
Primary Purpose: Diagnostic

Condition

• Lung Cancer
• Radiation Fibrosis
• Radiation Induced Lung Injury
• Pancreas Cancer

Intervention

Drug: [68Ga]CBP8

Up to 15 mCi of [68Ga]CBP8 will be administered to each subject. Each subject will undergo baseline imaging prior to radiation and again 3-6 months after radiation therapy.

Study Arms

Experimental: Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy

Lung cancer or pancreatic cancer patients will receive [68Ga]CBP8 and undergo PET imaging 1) prior to radiation therapy and 2) 3-6 months after radiation therapy

Intervention: Drug: [68Ga]CBP8

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2021): 72
• Original Estimated Enrollment (submitted: July 21, 2020): 40
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria for lung cancer subjects:

• Eligible patients will be those harboring locally advanced clinical stage I-III NSCLC who are not eligible for surgical resection, or those with 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.

Inclusion Criteria for pancreatic cancer subjects:

• Age ≥ 18 years.
• Life expectancy of greater than 3 months.
• Ability to understand and the willingness to sign a written informed consent document.
• Histologically or cytologically confirmed diagnosis of PDAC.
• Tumor should be confirmed with imaging based on the standard-of-care baseline abdominal CT performed within 1 month before study visit 1.
• Core samples for initial diagnosis must be available at the Department of Pathology at Massachusetts General Hospital.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational imaging and standard treatment regimen are eligible for this trial.
• Scheduled study visit 1 within 1 month prior to starting neoadjuvant chemoradiotherapy (CRT)
• Subjects undergo neoadjuvant chemotherapy followed by radiotherapy (CRT) as part of their standard clinical care and based on institutional standards.
• Scheduled surgical pancreas resection within 1 month after post-CRT study visit.
• Subjects are required to undergo pre-surgical CT of abdomen within 1 month after completion of standard neoadjuvant CRT as part of routine clinical work-up.

Exclusion Criteria for lung cancer subjects:

• 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;
• 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;
• Body weight of > 300 lbs (weight 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 lung cancer or smoking related lung disease,)
• Pneumonia or other acute respiratory illness within 6 weeks of study entry, pneumonia defined with elevated WBC, fever, infiltrate on CXR and need for antibiotics

Exclusion Criteria for pancreatic cancer subjects:

• History of radiotherapy to the upper abdomen in the past.
• History of reaction to MRI contrast (Gadoterate meglumine)
• Clinical or imaging diagnosis of acute pancreatitis within 6 weeks prior to study visit
• Participants with uncontrolled intercurrent illness or if determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening and/or during study).
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• 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 at each PET/MRI study visit;
• 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 PET-MRI table)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michael Lanuti, MD; 6176430193; mlanuti@mgh.harvard.edu

Contact: Shadi Esfahani, MD; AbdarEsfahani.Shadi@mgh.harvard.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04485286
• Other Study ID Numbers: 2020P001899; R44CA250771 ( U.S. NIH Grant/Contract ); K08CA259626 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Peter Caravan, Massachusetts General Hospital
• Original Responsible Party: Peter David Caravan, Massachusetts General Hospital, Professor of Radiology
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Lanuti, MD; Massachusetts General Hospital
• Principal Investigator: Shadi Esfahani, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: April 2023