Clinical trial NCT04309552: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Glioma
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: William Rhodes Center for Glioblastoma
First posted: 2020-03-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: DIAGNOSTIC

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.

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)

Primary outcomes:
measure: Quantitation of tumor hypoxia (FMISO) by measuring Dyn PET
timeFrame: 1 year
measure: Quantitation of proliferation (FLT) by measuring Dyn PET
timeFrame: 1 year
Secondary outcomes:
measure: FMISO/FLT PET Metrics and Molecular Biomarkers of Tissue Hypoxia, Tissue Angiogenesis, and Tissue Proliferation
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Sadek Nehmeh, PhD
role: PRINCIPAL_INVESTIGATOR
References: