MRI and PET Scan Using 18F-Fluoromisonidazole In Assessing Tumor Hypoxia in Patients With Newly Diagnosed Glioblastoma Multiforme
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00902577|
Recruitment Status : Active, not recruiting
First Posted : May 15, 2009
Last Update Posted : January 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma||Drug: 18F-Fluoromisonidazole Procedure: Magnetic Resonance Imaging Procedure: Positron Emission Tomography||Phase 2|
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 other).
III. To assess the correlation between highest tissue:cerebellum ratio [T/Cmax] and T/Bmax at baseline.
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 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI|
|Actual Study Start Date :||August 24, 2009|
|Estimated Primary Completion Date :||January 31, 2018|
Experimental: Diagnostic (MRI and PET using FMISO)
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.
Undergo FMISO PET scans
Other Names:Procedure: Magnetic Resonance Imaging
Other Names:Procedure: Positron Emission Tomography
Undergo FMISO PET scan
- Association of baseline FMISO PET uptake (HV and T/Bmax) and MRI parameters (Ktrans and CBV) with OS as assessed using Cox-regression model [ Time Frame: Up to 5 years after completion of study ]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.
- Association of baseline FMISO PET uptake (HV and T/Bmax) and MRI parameters (Ktrans and CBV) with TTP and PFS-6 as assessed using multi-variate Cox model and multi-variate Logistic regression model [ Time Frame: Up to 5 years after completion of study ]
Cox-regression model will be used to study the relationship between TTP and baseline FMISO PET uptake and MRI parameters. Logistic regression model will be used to study the relationship between PFS-6 and baseline FMISO PET uptake and MRI parameters. Uni-variate analysis will be carried out for each parameter individually. Any parameter that has achieved statistical significance (P=< 0.05) will be included.
Disease progression defined by Macdonald criteria: >= 25% increase of enhancing tumor area; Neurological status worsened; Stable or increased dose of steroids
- Correlation between other MRI parameters (T1Gd, VCI, small vessel CBV, ADC, NAA-Cho ratio, changes in BOLD signal, and T2 lesion volume) and OS, TTP, and PFS-6 [ Time Frame: Up to 5 years after completion of study ]
Other MRI parameters include: initial size of the lesion measured on T1 post Gd images [T1Gd], vessel caliber index [VCI], small vessel CBV, apparent diffusion coefficient [ADC], values measured from MR spectroscopy such as NAA-Cho ratio, changes in BOLD signal with transient exposure to hyperoxia, and T2 lesion volume.
Cox-regression model will be used to study the relationship between OS and other MRI parameters. Logistic regression model will be used to study the relationship between PFS-6 and other MRI parameters. Uni-variate analysis will be carried out for each parameter individually.
- Correlation between T/Cmax and T/Bmax [ Time Frame: At baseline, week 4, and week 10 ]Pearson correlation coefficient and Spearman's rank correlation coefficient will be used to quantify the correlation between T/Cmax and T/Bmax.
- Reproducibility of the baseline FMISO PET uptake parameters as assessed by baseline "test" and "retest" PET scans [ Time Frame: Baseline and retest within 1 to 7 days after (but prior to the start of therapy) ]
The reproducibility of the baseline FMISO PET will be quantified through intra-class correlation coefficient (ICC) which is defined as the ratio of σb^2 and (σb^2+ σc^2) where σb^2 is the variance of measurements between participants and σc^2 is the variance of measurements within participants.
For a subset of 15 participants who enroll in the test-retest substudy only. Patients must be scanned using the same ACRIN-approved PET scanner used for trial qualification, using the same protocol-specific parameters consistently at each time point.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00902577
|United States, Alabama|
|University of Alabama at Birmingham Cancer Center|
|Birmingham, Alabama, United States, 35233|
|United States, California|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Mount Sinai Hospital|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|American College of Radiology Imaging Network|
|Philadelphia, Pennsylvania, United States, 19103|
|University of Pennsylvania/Abramson Cancer Center|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Washington|
|University of Washington Medical Center|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Elizabeth Gerstner||American College of Radiology Imaging Network|