T-Cell PET Imaging With [18F]F-AraG in Lung Cancer

T-Cell PET Imaging With [18F]F-AraG and Radiomics to Guide Combined Radiation and Systemic Immune Modulating Therapies

This is a single-center cross-sectional imaging study in patients with localized lung cancer undergoing immunotherapy with or without stereotactic radiation therapy as part of the companion clinical trial (NCT03217071; Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer). Each patient will undergo a single [18F]F-AraG PET exam as part of this study. [18F]F-AraG will be administered at a single time point intravenously prior to PET imaging. Whole-body PET will be acquired along with a whole body low dose CT (PET/CT) used for attenuation correction and anatomic localization of [18F]F-AraG uptake, SUV calculation, and volumetric selection for radiomic analyses.

Study Overview

• Status: Withdrawn
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: [18F]F-Ara-G; Radiation: PET/CT scan

Detailed Description

This is a single-center cross-sectional imaging study in patients with localized lung cancer undergoing immunotherapy with or without stereotactic radiation therapy as part of the companion clinical trial (NCT03217071; Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer). Each patient will undergo a single [18F]F-AraG PET exam as part of this study. [18F]F-AraG will be administered at a single time point intravenously prior to PET imaging. Whole-body PET will be acquired along with a whole body low dose CT (PET/CT) used for attenuation correction and anatomic localization of [18F]F-AraG uptake, SUV calculation, and volumetric selection for radiomic analyses.

A total of 20 patients will be enrolled over an accrual period of approximately 12 months. Approximately 10 patients will be enrolled in the immunotherapy alone cohort and approximately 10 patients will be enrolled in the immunotherapy and stereotactic radiation therapy cohort.

Patients will be evaluated one day and one week via telephone after each radiopharmaceutical injection for safety follow-up. All adverse events will be recorded. Due to the noninvasive and non-therapeutic nature of the study, potential risks of the study are anticipated to be low.

• Study Type: Interventional
• Phase: Phase 2

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:

1. Age greater than or equal to 18 years
2. Histologically or cytologically documented stage I-IIIA non-small cell lung cancer (NSCLC)
3. Eligible for with plan to undergo immunotherapy alone or both immunotherapy and stereotactic radiation therapy as part of NCT03217071
4. In female patients, negative pregnancy test with no plans to become pregnant during the duration of the study
5. Able to provide informed consent and follow the study guidelines

Exclusion Criteria:

1. Female patients who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1 - Immunotherapy Alone; Approximately 10 patients will be enrolled in the immunotherapy alone cohort under a larger two-year industry-funded, investigator-initiated single-institution, phase II, open-label clinical trial (NCT03217071; Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer) in which patients with stage I-IIIA non-small cell lung cancer (NSCLC) are randomized to receive two cycles of systemic immunotherapy (pembrolizumab, a PD-1 inhibitor) with or without immune-priming stereotactic radiation therapy (SRT, 12 Gy) to the lateral half of the primary lung tumor prior to resection.	Drug: Pembrolizumab; All study participants will receive pembrolizumab every 3 weeks, for 2 cycles.; Other Names: Keytruda; Drug: [18F]F-Ara-G; Administered after two cycles of immunotherapy +/- stereotactic radiation therapy as part of the PET/CT scan.; Other Names: 2'-deoxy-2'-[18F]fluoro-9-β-Darabinofuranosylguanine; Radiation: PET/CT scan; Scan will be done after two cycles of immunotherapy +/- stereotactic radiation therapy.
EXPERIMENTAL: Cohort 2 - Immunotherapy with Stereotactic Radiation; Approximately 10 patients will be enrolled in the immunotherapy with stereotactic radiation therapy cohort under a larger two-year industry-funded, investigator-initiated single-institution, phase II, open-label clinical trial (NCT03217071; Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer) in which patients with stage I-IIIA non-small cell lung cancer (NSCLC) are randomized to receive two cycles of systemic immunotherapy (pembrolizumab, a PD-1 inhibitor) with or without immune-priming stereotactic radiation therapy (SRT, 12 Gy) to the lateral half of the primary lung tumor prior to resection.	Drug: Pembrolizumab; All study participants will receive pembrolizumab every 3 weeks, for 2 cycles.; Other Names: Keytruda; Drug: [18F]F-Ara-G; Administered after two cycles of immunotherapy +/- stereotactic radiation therapy as part of the PET/CT scan.; Other Names: 2'-deoxy-2'-[18F]fluoro-9-β-Darabinofuranosylguanine; Radiation: PET/CT scan; Scan will be done after two cycles of immunotherapy +/- stereotactic radiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between number of infiltrating CD3+ T cells/μm2 in the non-small cell lunger cancer thoracotomy specimen as quantified by immunohistochemistry and the activated T-cell concentration as determined by [18F]F-AraG PET (SUVmax)	The correlation between number of infiltrating CD3+ T cells/μm2 in the non-small cell lunger cancer thoracotomy specimen as quantified by immunohistochemistry and the activated T-cell concentration as determined by [18F]F-AraG PET (SUVmax)	Baseline (after two cycles of pembrolizumab)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The detection of out-of-target radiation-mediated immune modulation in lymph nodes using [18F]F-AraG PET	The detection of out-of-target radiation-mediated immune modulation in lymph nodes using [18F]F-AraG PET	Baseline (after two cycles of pembrolizumab)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: CellSight Technologies, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 26, 2017
• Primary Completion (ACTUAL): October 15, 2019
• Study Completion (ACTUAL): October 15, 2019

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (ACTUAL): October 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: 176513; NCI-2018-02158 (OTHER: NCI Clinical Trials Reporting Program (CTRP))

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