Tumor Hypoxia and Proliferation in Patients With High-Grade Glioma

Phase 1

Active, not recruiting

• Conditions: Glioma
• Interventions: Drug: 18F-FMISO PET; Drug: 18F-FLT PET

• Registration Number: NCT04309552
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

This is a pilot study to assess a new methodology developed for High Grade Glioma (HGG). FMISO PET (Fluoromisonidazole-PET) allows researchers to study whether tumor cells lack oxygen (hypoxia). FLT PET (Fluorodeoxythymidine-PET) allows researchers to study the increase in the number of cells as a result of cell growth and cell division (proliferation). Tumors that have low oxygen levels and/or are dividing fast shall resist to standard cancer treatment. The study will compare FMISO PET and FLT PET imaging techniques with molecular biomarkers of hypoxia, angiogenesis, and cellular proliferation in tissue. proliferation).This information could help researchers develop new treatment techniques to better treat cancer.

Detailed Description

This is a pilot study to assess a novel methodology recently developed to simultaneously image tumor hypoxia and proliferation by means of simultaneous FMISO and FLT PET acquisition. FMISO (18F-Fluoromisonidazole) PET is a non-invasive method for detecting tumor hypoxia in solid tumors. FLT (3'-deoxy-3'\[(18)F\]-fluorothymidine) PET is a non-invasive method to image Cell proliferation rate. Imaging of tumor hypoxia and proliferation with FMISO and FLT PET respectively are two very well established techniques in in high-grade glioma. The long-term goal of this proposal is to establish clinically robust methodology to simultaneously image multiple tumor hallmarks. The central hypothesis is that combined information from multiple tumor hallmarks will offer complementary information about the underlying physiological processes, and will yield synergistic prognostic and predictive values. The rationale is that these findings will enhance the understanding of the underlying biology and pathophysiology, and will open new therapeutic strategies to target radioresistant and highly aggressive regions within the tumor, as well as aiding in the development of imaging theragnostics. The method used in this proposal is based on our previous work on simultaneous imaging of FMISO/FLT PET, and is facilitated by prior knowledge of the tissue pharmacokinetics, and an ability to distinguish the two radiotracers fractions in blood by thin-layer chromatography (TLC). The study will compare FMISO and FLT imaging findings with those from molecular biomarkers of hypoxia, angiogenesis, and cellular proliferation in tissue.

Study Timeline

• Study First Submitted: 2020-03-12
• Study First Submitted QC: 2020-03-12
• Study First Posted: 2020-03-16
• Study Start: 2021-02-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-28
• Last Update Posted: 2025-01-29
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Male or female ≥ 18 years of age
• Documentation of a suspected HGG diagnosis based on clinical and MRI findings

Exclusion Criteria

• Pregnant or breastfeeding
• Contraindications to receiving Positron Emission Tomography (PET) imaging (e.g. claustrophobia)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High Grade Glioma (HGG)	18F-FMISO PET	Thirty newly diagnosed treatment-naïve subjects with suspected HGG based on clinical presentation and MRI findings and undergoing surgical planning will be accrued in this study.
High Grade Glioma (HGG)	18F-FLT PET	Thirty newly diagnosed treatment-naïve subjects with suspected HGG based on clinical presentation and MRI findings and undergoing surgical planning will be accrued in this study.

Primary Outcome Measures

Name	Time	Method
Quantitation of tumor hypoxia (FMISO) by measuring Dyn PET	1 year	Simultaneous quantitation of tumor hypoxia (FMISO): Dyn-PET data will be acquired with staggered FMISO/FLT injections and then the two radiotracer signals will be deconvolved using our novel pharmacokinetics modeling approach (Sections D2, D3, and D4 of Preliminary Data)
Quantitation of proliferation (FLT) by measuring Dyn PET	1 year	Simultaneous quantitation of proliferation (FLT): Dyn-PET data will be acquired with staggered FMISO/FLT injections and then the two radiotracer signals will be deconvolved using our novel pharmacokinetics modeling approach (Sections D2, D3, and D4 of Preliminary Data)

Secondary Outcome Measures

Name	Time	Method
FMISO/FLT PET Metrics and Molecular Biomarkers of Tissue Hypoxia, Tissue Angiogenesis, and Tissue Proliferation	1 year	FMISO/FLT images will be used for intraoperative neuro-navigation and targeted sampling of FMISO and FLT avid tumor subregions prior to tumor excision. PET metrics will be correlated with immuno-histochemistry (IHC) analyses for HIF-1α, Ki-67, VEGF, EGFR, IDH1, and pimonidazole, as well as molecular analyses of TERT promoter mutation status. Results will be based on a composite score from all measurements. These markers contribute to disease progression in HGG.

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States