[18F]-AraG for the Detection of T-Cell Activation in Advanced Non-small Cell Lung Cancer Patients Undergoing PD-1/PD-L1-Directed Therapy

Imaging of T-Cell Activation With [18F]-AraG in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Undergoing PD-1/PD-L1-Directed Therapy

This trial studies how well [18F]-AraG works in detecting T-cell activation in patients with non-small cell lung cancer that has spread to other places in the body (advanced), who are undergoing PD-1/PD-L1-directed therapy. [18F]-AraG is a "radiotracer" which attaches to immune cells directed at the cancer and shines a light that can be seen using a special camera, called a "positron emission tomography" or "PET" scanner. [18F]-AraG may improve the ability to detect a response of the cancer in the body to immunotherapy.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Lung Non-Small Cell Carcinoma; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Advanced Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Drug: Fluorine F 18 Ara-G

Detailed Description

PRIMARY OBJECTIVES:

I. To quantify fluorine F 18 Ara-G ([18F]-AraG) uptake (standardized uptake value [SUV]) in advanced non-small cell lung cancer (NSCLC) tumor (primary, nodal, and metastatic sites) at baseline and after 1 dose of anti-PD-1/PD-L1 therapy in both patients treated with PD-1/PD-L1 monotherapy and in patients treated with immunotherapy/chemotherapy combination therapy.

II. To correlate change in [18F]-AraG uptake before and after the start of therapy with radiographic response in patients treated with immunotherapy.

OUTLINE:

Patients receive [18F]-AraG intravenously (IV) and then undergo PET/CT over 2 hours at baseline and within 2 weeks after starting immunotherapy. Patients may also undergo blood sample collection.

After completion of study treatment, patients are followed for up to 12 months.

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• This study is open to all adult subjects with histological confirmation of NSCLC planned to undergo treatment with a PD-1 or PD-L1 inhibitor either as monotherapy or as combination therapy with concurrent chemotherapy as treatment for advanced/metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3 at the time of enrollment
• Patient with life expectancy >= 24 weeks from the time of screening to the study
• Ability to sign and understand the Institutional Review Board (IRB)-approved consent form in English
• Ability to remain motionless for up to 30 minutes per scan

Exclusion Criteria:

• Patients with severe claustrophobia (patients with milder forms of claustrophobia that can be successfully allayed with oral anxiolytic therapy are allowed)
• Severe impaired renal function with estimated glomerular filtration rate < 30 mL/min/1.73 m^2 and/or on dialysis
• Pregnancy
• Breast feeding an infant
• Prior treatment with anti-PD-1/PD-L1 inhibitor
• Localized/locally advanced disease with anti PD-1/PD-L1 given as consolidation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diagnostic ([18F]-AraG); Patients receive [18F]-AraG IV and then undergo PET/CT over 2 hours at baseline and within 2 weeks after starting immunotherapy. Patients may also undergo blood sample collection.	Drug: Fluorine F 18 Ara-G; Given IV; Other Names: 18F-F-Ara-G; [18F]F-ara-G; [18F]F-AraG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorine F 18 Ara-G ([18F]-AraG) uptake values in advanced non-small cell lung cancer (NSCLC) before and after treatment with anti-PD-1/PD-L1 therapy obtained	The positron emission tomography (PET) images will be interpreted qualitatively and semi-quantitatively on a lesion-by-lesion basis. Semi-quantitative analysis will be employed as follows: (a) Regions of interest (ROIs) will be placed around tracer avid foci suspicious for malignancy in order to obtain standardized uptake value (SUV) parameters, including maximum SUV (SUVmax), SUVpeak, SUVmean; (b) SUV data will be recorded along with volumetric and positional information in a standardized form.	Baseline up to within 2 weeks after starting immunotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in SUV	All SUV measurements will be summarized descriptively, separately for baseline and follow-up. Descriptive statistics for the SUVs will be done on a subject basis and a per lesion basis. Graphical summaries including box plots will be prepared to illustrate distributions and detect outliers or other findings; numerical summaries will include, mean, standard deviation (SD), median, and range as appropriate. For each target lesion, the scan 1 and scan 2 SUV will be determined and compared. A mixed-model repeated-measures analysis of variance (ANOVA) will be used to estimate the mean change in SUV from scan 1 to scan 2, allowing for possible need to account for between-patient random variation both in baseline level of SUV and amount of change. The primary result will be an estimate of the mean change in SUV, with a 95% confidence interval, along with the between patient and within-patient, between-lesion variation.	Baseline up to within 2 weeks after starting immunotherapy
Correlation between [18F]-AraG uptake and clinical response		Baseline up to within 2 weeks after starting immunotherapy

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Cancer Institute (NCI); CellSight Technologies, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2019
• Primary Completion (ACTUAL): March 12, 2020
• Study Completion (ACTUAL): March 12, 2020

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (ACTUAL): December 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Antineoplastic Agents; 9-arabinofuranosylguanine
• Other Study ID Numbers: 1471901; P30CA093373 (U.S. NIH Grant/Contract); NCI-2019-07768 (REGISTRY: CTRP (Clinical Trial Reporting Program)); CCHO030 (OTHER: University of California Davis Comprehensive Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No