Tumor Hypoxia and Proliferation in Patients With High-Grade Glioma

NCT04309552 | Suspended Phase 1 FDA Drug

• 1 other identifier: 20-02021553
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioma

Outcome Measures

Primary Outcomes (2)

• Quantitation of tumor hypoxia (FMISO) by measuring Dyn PET

  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)

  1 year

• Quantitation of proliferation (FLT) by measuring Dyn PET

  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)

  1 year

Secondary Outcomes (1)

• FMISO/FLT PET Metrics and Molecular Biomarkers of Tissue Hypoxia, Tissue Angiogenesis, and Tissue Proliferation

  1 year

Study Arms (1)

High Grade Glioma (HGG)

EXPERIMENTAL

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.

Drug: 18F-FMISO PET; Drug: 18F-FLT PET

Interventions

18F-FMISO PET DRUG

Suspected HGG subjects will undergo combined FMISO/FLT dyn-PET at baseline as part of surgical planning. Dyn-PET images will be acquired with staggered FMISO/FLT injections using a lag time of 50 minutes. Preoperatively FMISO/FLT dyn-PET data will be used for intraoperative neuro-navigation and targeted sampling of PET avid tumor subregions prior to tumor excision. Paraffin blocks will be analyzed with immuno-histochemistry and in situ hybridization for HIF-1α, Ki-67, VEGF, EGFR, IDH, and pimonidazole, as well as TERT. FMISO-PET uptake rate, k3, (surrogate for hypoxia) and FLT-PET influx rate, Ki (surrogate for proliferation) will be correlated with time to progression, progression-free survival at 9 months, and overall survival (OS) at 1 year.

Also known as: 18F-Fluoromisonidazole

High Grade Glioma (HGG)

18F-FLT PET DRUG

Suspected HGG subjects will undergo combined FMISO/FLT dyn-PET at baseline as part of surgical planning. Dyn-PET images will be acquired with staggered FMISO/FLT injections using a lag time of 50 minutes. Preoperatively FMISO/FLT dyn-PET data will be used for intraoperative neuro-navigation and targeted sampling of PET avid tumor subregions prior to tumor excision. Paraffin blocks will be analyzed with immuno-histochemistry and in situ hybridization for HIF-1α, Ki-67, VEGF, EGFR, IDH, and pimonidazole, as well as TERT. FMISO-PET uptake rate, k3, (surrogate for hypoxia) and FLT-PET influx rate, Ki (surrogate for proliferation) will be correlated with time to progression, progression-free survival at 9 months, and overall survival (OS) at 1 year.

Also known as: 3'-deoxy- 3'[(18)F]-fluorothymidine

High Grade Glioma (HGG)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• William Rhodes Center for Glioblastoma: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

fluoromisonidazole

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Sadek Nehmeh, PhD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single center, prospective, non-randomized trial of 30 newly diagnosed patients with suspected HGG undergoing surgical planning will be enrolled to undergo combined FMISO/FLT PET at baseline. Blood samples will be drawn during PET acquisition. Preoperatively FMISO/FLT PET data will be used for intraoperative neuro-navigation and targeted sampling of PET avid tumor subregions prior to tumor excision. Paraffin blocks will be analyzed with immuno-histochemistry and in situ hybridization. Longitudinal clinical data will be collected from the medical record for standard of care visits to the oncology and surgical clinics. Imaging data from research scans will be correlated with time to progression, progression-free survival at 9 months, and overall survival (OS) at 1 year post baseline assessment.

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 16, 2020
• Study Start: February 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)