Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI
I. To determine the association of baseline FMISO PET uptake (hypoxic volume [HV]), highest
tumor:blood ratio [T/Bmax]) and MRI parameters (Ktrans, CBV) with overall survival (OS) in
participants with newly diagnosed GBM.
I. To determine the association of baseline FMISO PET uptake (HV, T/Bmax) and MRI parameters
(Ktrans, CBV) with time to progression (TTP) and 6-month progression free survival (PFS-6)
in participants with newly diagnosed GBM.
II. To assess the reproducibility of the baseline FMISO PET uptake parameters by
implementing baseline "test" and "retest" PET scans (performed within 1 to 7 days of each
III. To assess the correlation between highest tissue:cerebellum ratio [T/Cmax] and T/Bmax
IV. To assess the correlation between other MRI parameters (T1Gd, VCI, CBV-S, ADC, NAA-Cho,
BOLD, T2) and OS, TTP, and PFS-6.
OUTLINE: This is a multicenter study.
Two weeks before initiation of chemoradiotherapy with temozolomide, patients undergo MRI and
PET scan using FMISO. A subset of 15 patients undergo FMISO PET scans approximately 1 week
before chemoradiotherapy. Blood samples are collected at baseline and periodically during
study to compare image measures of tissue uptake of FMISO to blood concentrations. Tumor
samples are collected from diagnostic biopsy or surgery for analysis of tumor hypoxic
markers and methylguanine methyl transferase by immunohistochemical and PCR assays.
After completion of study therapy, patients are followed up every 3 months for up to 5
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Association of baseline FMISO PET uptake (HV and T/Bmax) and MRI parameters (Ktrans and CBV) with OS as assessed using Cox-regression model
The number of pixels in the tumor volume with a T/B ratio > 1.2, indicating hypoxia, is multiplied by the known volume/voxel for the scanner to yield milliliter units to measure the HV. T/Bmax is the pixel in the tumor region with the maximum T/B (tumor:blood) ratio. HV depicts the volume of tumor that has crossed the threshold for hypoxia and T/Bmax depicts the magnitude of the hypoxia. Uni-variate analysis will be carried out for each parameter individually. Any parameter that has achieved statistical significance (P ≤ 0.05) will be included in the multi-variate Cox model.
Up to 5 years after completion of study
American College of Radiology Imaging Network
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Dana-Farber Harvard Cancer Center||Boston, Massachusetts 02115|
|American College of Radiology Imaging Network||Philadelphia, Pennsylvania 19103|
|Johns Hopkins University CCOP||Baltimore, Maryland 21287|