search
Back to results

Tumor Hypoxia and Proliferation in Patients With High-Grade Glioma

Primary Purpose

Glioma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
18F-FMISO PET
18F-FLT PET
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Glioma

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Weill Cornell Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

High Grade Glioma (HGG)

Arm Description

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.

Outcomes

Primary Outcome Measures

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)
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)

Secondary Outcome Measures

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

Full Information

First Posted
March 12, 2020
Last Updated
April 17, 2023
Sponsor
Weill Medical College of Cornell University
Collaborators
William Rhodes Center for Glioblastoma
search

1. Study Identification

Unique Protocol Identification Number
NCT04309552
Brief Title
Tumor Hypoxia and Proliferation in Patients With High-Grade Glioma
Official Title
A Phase-I Trial for Simultaneous Imaging of Tumor Hypoxia and Proliferation in Patients With Treatment- Naïve High-Grade Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
William Rhodes Center for Glioblastoma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High Grade Glioma (HGG)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
18F-FMISO PET
Other Intervention Name(s)
18F-Fluoromisonidazole
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
18F-FLT PET
Other Intervention Name(s)
3'-deoxy- 3'[(18)F]-fluorothymidine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Quantitation of tumor hypoxia (FMISO) by measuring Dyn PET
Description
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)
Time Frame
1 year
Title
Quantitation of proliferation (FLT) by measuring Dyn PET
Description
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)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
FMISO/FLT PET Metrics and Molecular Biomarkers of Tissue Hypoxia, Tissue Angiogenesis, and Tissue Proliferation
Description
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sadek Nehmeh, PhD
Phone
212-746-4645
Email
san2028@med.cornell.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Eileen Chang
Phone
646-962-6282
Email
eic2002@med.cornell.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sadek Nehmeh, PhD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sadek Nehmeh, Ph.D
Phone
212-746-4645
Email
san2028@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Eileen Chang
Phone
646-962-6282
Email
eic2002@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Sadek Nehmeh, Ph.D

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Tumor Hypoxia and Proliferation in Patients With High-Grade Glioma

We'll reach out to this number within 24 hrs