Pseudo-Simultaneous Imaging of Tumor Hypoxia and Proliferation in HNC Patients Using PET/CT

A Pilot Study to Assess the Feasibility of Pseudo-Simultaneous Imaging of Tumor Hypoxia and Proliferation in Head and Neck Cancer Patients Using PET/CT

66% of HNC patients present with advanced-stage disease at initial diagnosis. The 5-year survival rates for stages IVa, IVb, and IVc are 32%, 25%, and <4% respectively. Accurate pre-treatment staging is vital in determining the optimum procedure for the management of HNC. Early identification of non-responders may allow modification of their treatment through the introduction of more intensive therapies. Identifying prognostic factors that predict patient outcome will ultimately lead to new treatment regimens. Tumor hypoxia and proliferation are two key characteristics of cancer that were shown to correlate with poor response to treatment in HNC. In this proposal, the investigators assess the prognostic values of these two markers. Combining information from these two biological markers shall result in prognostic information superior to those of any of the two separately. Imaging those vital tumor characteristics simultaneously shall provide more coherent assessment of tumor microenvironment than does registration of corresponding images acquired in different imaging session, thus subject to uncertainties resulting from transient biologic changes and image registration process. The investigators propose to use a method that the investigators previously developed to simultaneously and non-invasively image tumor hypoxia (FMISO-PET) and proliferation (FLT-PET) within a single PET/CT study. CT Perfusion scan will be performed 1st, followed by PET imaging with staggered FMISO and FLT injections. FMISO and FLT signals will be separated retrospectively using kinetic modeling. The investigators believe imaging tumor hypoxia and cell proliferation simultaneously yield information underpinning for image-guided and radiobiological based dose painting, adaptive therapy, and patient medical management. If successful, this pilot study will constitute the basis for a NIH grant proposal that aims to improve treatment outcome assessment in HNC.

Study Overview

• Status: Withdrawn
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Diagnostic test: PET/CT Imaging

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Citigroup Biomedical Imaging Center

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

Subject Inclusion Criteria:

• Pathologic Confirmation of HNC
• No prior treatment for this diagnosis of HNC
• Patient to be treated with Radio-Therapy
• Age >= 18 years old
• Karnofsky performance status >= 70%
• Women of childbearing age must have a negative blood pregnancy test.

Exclusion Criteria:

• Women who are pregnant or breast-feeding.
• Severe diabetes (fasting blood glucose > 200- mg/dl)
• Adults who are unable to consent
• Patients who do not agree to share and store data History of lack of tolerance of the standard of care FDG-PET scan previously obtained
• History of previous intolerance of either FMISO or FLT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Repeatability of FLT kinetics; Radiotracer: 18F-FLT Dose: 10 mCi Frequency: Two baseline PET/CT at baseline up to 3 days apart.	Diagnostic test: PET/CT Imaging; PET/CT Imaging of tumor hypoxia and proliferation
Experimental: Pseudo-Simultaneous FMISO/FLT PET/CT Imaging; Radiotracer: 18F-FLT and 18F-FLT Dose and Frequency: 8 mCi 18F-FLT and 8 mCi 18F-FLT on Day1, the 8mCi 18F-FLT on Day2	Diagnostic test: PET/CT Imaging; PET/CT Imaging of tumor hypoxia and proliferation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simultaneous Imaging of tumor hypoxia and proliferation	To assess the feasibility to tease out the FMISO and FLT kinetics in simultaneous FMISO/FLT PET/CT imaging. FMISO and FLT kinetic parameters will be measured from the combined FMISO/FLT dynamic study. The accuracy of those measurements will be tested by comparing the FLT kinetic measurements deduced from the combined FMISO/FLT study on day1 with those from the sole FLT study of day2.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repeatability of FLT	To assess the repeatability of FLT kinetics. Subjects will undergo two dynamic FLT PET studies up to 3 days apart. The repeatability of the corresponding kinetic parameters from the two studies will be measured using statistical methods (e.g. Bland-Altman analysis)	1 year

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Sadek Nehmeh, Ph.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 7, 2018

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Signs and Symptoms, Respiratory; Head and Neck Neoplasms; Hypoxia
• Other Study ID Numbers: 1703018046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

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.: Yes