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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-01912 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000640413 | Registry Identifier | ClinicalTrials.gov | |
| ACRIN 6684 | Other Identifier | American College of Radiology Imaging Network | |
| ACRIN-6684 | Other Identifier | CTEP | |
| U01CA080098 | U.S. NIH Grant/Contract | View source |
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This phase II trial is studying how well positron emission tomography (PET) scan using 18F-fluoromisonidazole works when given together with magnetic resonance imaging (MRI) ) in assessing tumor hypoxia in patients with newly diagnosed glioblastoma multiforme (GBM). Diagnostic procedures, such as MRI and PET scan using 18F-fluoromisonidazole (FMISO), may help predict the response of the tumor to the treatment and allow doctors to plan better treatment.
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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 (for example Gadolinium-enhanced T1-weighted (T1Gd), vessel caliber index (VCI), , CBV-S, apparent diffusion coefficient (ADC) , N-acetylaspartate (NAA) to choline (Cho) ratio, blood oxygenation level-dependent (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 Polymerase chain reaction (PCR) assays.
After completion of study therapy, patients are followed up every 3 months for up to 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diagnostic (MRI and PET using FMISO) | Experimental | Two weeks before initiation of chemoradiotherapy with temozolomide, patients undergo MRI (DSC, DCE,DWI and MRS) and PET scan using FMISO. A subset of 15 patients undergo FMISO PET scans approximately 1 week before chemoradiotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FMISO | Drug | FMISO PET scans |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Association of Baseline FMISO PET and MRI Features With OS as Assessed Using Cox-regression Model | Overall Survival (OS) was evaluated every 3 months through end of the study (up to 5 years). A variety of continuous quantitative (functional) imaging features measuring abnormal tumor vasculature (MRI) and hypoxia (FMISO) were evaluated at baseline for their association with Survival time. Features include PET Hypoxia measures: Peak standardized uptake values (SUVpeak); maximum tumor:blood ratio (T/Bmax); and Hypoxia Volume (HV) DCE MRI perfusion measures: Mean/median volume transfer constant for gadolinium between blood plasma and the tissue extravascular extracellular space (ktrans) DSC MRI tumor vasculature: Normalized Relative cerebral blood volume (nRCBV); and Cerebral blood flow (CBF) DWI MRI magnitude of diffusion of water through tissue (cell density): Apparent diffusion coefficient (ADC) using low and high Gaussian distributions | "assessed from baseline up to 5 years, survival status at 1-year reported |
| Measure | Description | Time Frame |
|---|---|---|
| Association of Baseline FMISO PET and MRI Features With Time-to-Progression (TTP) | Disease progression was defined by Macdonald criteria. PFS was evaluated every 3months through the end of study (up to 5yrs), features were measured at baseline. Quantitative imaging features measuring abnormal tumor vasculature (MRI) and hypoxia (FMISO) were evaluated for their association with TTP (cox model) and to discriminate between responders and non-responders at 6 and 9 mos (PFS6 and PFS9) (logistic) Features include PET Hypoxia measures: Peak standardized uptake values (SUVpeak); maximum tumor:blood ratio (T/Bmax); and Hypoxia Volume (HV) DCE MRI perfusion measures: Mean/median volume transfer constant for gadolinium between blood plasma and the tissue extravascular extracellular space (ktrans) DSC MRI tumor vasculature: Normalized Relative cerebral blood volume (nRCBV); and Cerebral blood flow (CBF) DWI MRI magnitude of diffusion of water through tissue (cell density): Apparent diffusion coefficient (ADC) using low and high Gaussian distributions |
| Measure | Description | Time Frame |
|---|---|---|
| Overall and Progression Free Survival | Disease progression was defined by Macdonald criteria. Survival and Progression were evaluated every 3months and at the end of study (up to 5 years) and time to event evaluated. | Baseline, every 3 months through study completion (up to 5 years for progression and survivorship) |
Inclusion Criteria:
Must be able to provide a written informed consent
Newly diagnosed glioblastoma multiforme (GBM), World Health Organization (WHO) grade IV based on pathology confirmation
Residual tumor after surgery (amount of residual tumor will not impact patient eligibility and visible residual disease can include T2/FLAIR hyperintensity)
Scheduled to receive standard fractionated radiation therapy
Scheduled to receive Temozolomide (TMZ) in addition to radiation therapy
Karnofsky Performance Score > 60
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Gerstner | American College of Radiology Imaging Network | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham Cancer Center | Birmingham | Alabama | 35233 | United States | ||
| USC / Norris Comprehensive Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29902200 | Result | Ratai EM, Zhang Z, Fink J, Muzi M, Hanna L, Greco E, Richards T, Kim D, Andronesi OC, Mintz A, Kostakoglu L, Prah M, Ellingson B, Schmainda K, Sorensen G, Barboriak D, Mankoff D, Gerstner ER; ACRIN 6684 trial group. ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy. PLoS One. 2018 Jun 14;13(6):e0198548. doi: 10.1371/journal.pone.0198548. eCollection 2018. | |
| 27185374 | Result |
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All participants were scheduled to receive both FMISO and MRI (DCE, DSC, DWI, MRS) imaging two weeks before initiation of chemoradiotherapy with temozolomide
Fifty patients with newly diagnosed GBM were enrolled from 11 academic centers in the United States.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Newly Diagnosed Glioblastoma Multiforme Patients | Patients with Newly diagnosed GBM scheduled to have FMISO Positron Emission Tomography (PET) two weeks before initiation of chemoradiotherapy with temozolomide, with diagnostic DCE/DSE/DWI MRI |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 24, 2012 |
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| MRI | Other | Undergo MRI |
|
|
| PET | Other | Undergo FMISO PET scan |
|
|
| MRS | Other |
|
|
| assessed from baseline up to 5 years, progression status at months 6 and 9 reported |
| Reproducibility of the Baseline FMISO PET Uptake Parameters as Assessed by Baseline "Test" and "Retest" PET Scans | Reproducibility, defined as the variation of repeated measurements in an experiment performed under the same conditions, will be measured as the within subject coefficient of variation with upper an lower repeatability coefficients (LRC, URC) computed as percents from log-transformed data, per Velaquez, et al (J Nucl Med. 2009 Oct;50(10):1646-54. doi: 10.2967/jnumed.109.063347. Epub 2009 Sep 16. PMID: 19759105 ). Where Within Subject Coefficient of Variation (wCV) is a percentage defined as wCV(%)=100* (exp( SD[ld]/√2) - 1) and LRC and URC are calculated as: RC=100 (exp(±1.96 SD[ld]) -1). here SD[ld] is the standard deviation of the difference of the log-transformed PET measurements. These bounds provide an estimate of the lower and upper bounds of percent change observed between scans for each measurement. | Baseline and retest within 1 to 7 days after (but prior to the start of therapy) |
| Correlation Between T/Cmax and T/Bmax | Pearson correlation coefficient will be used to quantify the correlation between T/Bmax, the maximum tissue-to-blood ratio activity value, and T/Cmax, the tissue-to-cerebellum activite value Since T/Cmax does not requiring blood sampling and is image derived, a high correlation would indicate that T/Cmax could be an advantageous surrogate for T/Bmax. | At baseline |
| Correlation Between MRS Markers and MR Imaging Markers of Vascularity as Well as Between MRS Markers and PET Markers of Tumor Hypoxia | Correlation between MRS markers and MR imaging markers and PET markers of tumor hypoxia MRS markers include: NAA/Cho, Cho/Cr, Lac/Cr, and Lac/NAA measured within tumor and at the periphery. MR imaging markers of vascularity include: CBV, CBF, and ktrans PET tumor hypoxia marker: SUVmax | baseline |
| SUVpeak and T/Bmax as Measures of Tumor Hypoxia |
The FMISO image data were normalized by the average blood activity to produce pixel level tissue-to-blood ratio (T/B) values for all image slices. And the severity of the hypoxia was determined by the pixel with the maximum T/B value (TBmax). FMISO SUVpeak was determined as the average SUV from a 1 cm circular ROI centered over the hottest pixel. Since FMISO selectively binds to hypoxic tissues, SUVpeak within a region provides a measure of tumor hypoxia. |
| baseline |
| Hypoxic Volume as a Measure of Tumor Hypoxia | The hypoxic volume (HV) was determined as the volume of pixels in the tumor on in the FMISO\PET with a tumor to blood activity ratio ≥ 1.2. HV is a measure of the spatial extent of tumor hypoxia (in milliliters) | baseline |
| DWI Apparent Diffusion Coefficient (ADC) | Apparent Diffusion Coefficient (ADC) measures water diffusion through tissue (mm^2/s). Cerebral infarction leads to diffusion restriction resulting in a low ADC signal in the infarcted area. A double Gaussian mixed model was fit to the ADC histogram and the mean of the lower and the mean of the higher ADC curves were evaluated | baseline |
| Normalized Relative Cerebral Blood Volume (nRCBV) and Normalized Cerebral Blood Flow (nCBF) | Relative cerebral blood volume (RCBV) maps, computed from the integral of ∆R2*(t), were corrected for leakage effects and normalized to normal appearing white matter (nRCBV); nRCBV provides a measure of tumor vasculature Cerebral blood flow (CBF) maps were was normalized to the mean of the region of interest (ROI) in normal appearing white matter (nCBF); nCBF provides a measure of vascular permeability and perfusion | baseline |
| Summary of Mean and Median Ktrans Across Participants. | ktrans is a measure of vascular permeability and reflects the rate of gadolinium moves from plasma to extravascular extracellular space (predominantly though blood flow and capillary leakage), which can be represented by the mean or median rate. Mean & Median ktrans within subject were computed using a matrix-based linearization method to fit tissue ∆R1(t) to the extended Tofts model. The mean across subjects is presented below (Mean (Mean-ktrans) and Mean(Median-Ktrans)) | baseline |
| Los Angeles |
| California |
| 90033 |
| United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | 21287 | United States |
| Massachusetts General Hospital Cancer Center | Boston | Massachusetts | 02114 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Mount Sinai Hospital | New York | New York | 10029 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland | Ohio | 44195 | United States |
| American College of Radiology Imaging Network | Philadelphia | Pennsylvania | 19103 | United States |
| University of Pennsylvania/Abramson Cancer Center | Philadelphia | Pennsylvania | 19104 | United States |
| University of Washington Medical Center | Seattle | Washington | 98195 | United States |
| Gerstner ER, Zhang Z, Fink JR, Muzi M, Hanna L, Greco E, Prah M, Schmainda KM, Mintz A, Kostakoglu L, Eikman EA, Ellingson BM, Ratai EM, Sorensen AG, Barboriak DP, Mankoff DA; ACRIN 6684 Trial Group. ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI. Clin Cancer Res. 2016 Oct 15;22(20):5079-5086. doi: 10.1158/1078-0432.CCR-15-2529. Epub 2016 May 16. |
| FMISO/PET | 3 images lost/Not Acquired 1 Image uninterpretable |
|
| DCE MRI | 2 images lost/Not Acquired 9 Image uninterpretable |
|
| DSE MRI | 2 images lost/Not Acquired 3 Image uninterpretable |
|
| DWI MRI | 3 images lost/Not Acquired |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Patients with newly diagnosed GBM who received both FMISO-PRT imaging two weeks before initiation of chemoradiotherapy with temozolomide
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| ID | Title | Description |
|---|---|---|
| BG000 | Newly Diagnosed Glioblastoma Multiforme Patients | 42 eligible, consented patients with newly diagnosed GBM who received both FMISO-PRT and MRI imaging two weeks before initiation of chemoradiotherapy with temozolomide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Median Tumor Volume | Median | Inter-Quartile Range | mm^3 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Association of Baseline FMISO PET and MRI Features With OS as Assessed Using Cox-regression Model | Overall Survival (OS) was evaluated every 3 months through end of the study (up to 5 years). A variety of continuous quantitative (functional) imaging features measuring abnormal tumor vasculature (MRI) and hypoxia (FMISO) were evaluated at baseline for their association with Survival time. Features include PET Hypoxia measures: Peak standardized uptake values (SUVpeak); maximum tumor:blood ratio (T/Bmax); and Hypoxia Volume (HV) DCE MRI perfusion measures: Mean/median volume transfer constant for gadolinium between blood plasma and the tissue extravascular extracellular space (ktrans) DSC MRI tumor vasculature: Normalized Relative cerebral blood volume (nRCBV); and Cerebral blood flow (CBF) DWI MRI magnitude of diffusion of water through tissue (cell density): Apparent diffusion coefficient (ADC) using low and high Gaussian distributions | FMISO-PET identifies the primary analysis population containing participants with interpretable FMISO images.The Evaluable study population consisted of enrolled GBM patients having an FMISO-PET procedure. Additional groups include functional MRI, with available/interpretable images. | Posted | Count of Participants | Participants | "assessed from baseline up to 5 years, survival status at 1-year reported |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Association of Baseline FMISO PET and MRI Features With Time-to-Progression (TTP) | Disease progression was defined by Macdonald criteria. PFS was evaluated every 3months through the end of study (up to 5yrs), features were measured at baseline. Quantitative imaging features measuring abnormal tumor vasculature (MRI) and hypoxia (FMISO) were evaluated for their association with TTP (cox model) and to discriminate between responders and non-responders at 6 and 9 mos (PFS6 and PFS9) (logistic) Features include PET Hypoxia measures: Peak standardized uptake values (SUVpeak); maximum tumor:blood ratio (T/Bmax); and Hypoxia Volume (HV) DCE MRI perfusion measures: Mean/median volume transfer constant for gadolinium between blood plasma and the tissue extravascular extracellular space (ktrans) DSC MRI tumor vasculature: Normalized Relative cerebral blood volume (nRCBV); and Cerebral blood flow (CBF) DWI MRI magnitude of diffusion of water through tissue (cell density): Apparent diffusion coefficient (ADC) using low and high Gaussian distributions | Posted | Count of Participants | Participants | assessed from baseline up to 5 years, progression status at months 6 and 9 reported |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Reproducibility of the Baseline FMISO PET Uptake Parameters as Assessed by Baseline "Test" and "Retest" PET Scans | Reproducibility, defined as the variation of repeated measurements in an experiment performed under the same conditions, will be measured as the within subject coefficient of variation with upper an lower repeatability coefficients (LRC, URC) computed as percents from log-transformed data, per Velaquez, et al (J Nucl Med. 2009 Oct;50(10):1646-54. doi: 10.2967/jnumed.109.063347. Epub 2009 Sep 16. PMID: 19759105 ). Where Within Subject Coefficient of Variation (wCV) is a percentage defined as wCV(%)=100* (exp( SD[ld]/√2) - 1) and LRC and URC are calculated as: RC=100 (exp(±1.96 SD[ld]) -1). here SD[ld] is the standard deviation of the difference of the log-transformed PET measurements. These bounds provide an estimate of the lower and upper bounds of percent change observed between scans for each measurement. | Analysis will be performed SUVmax and SUV Peak, average and maximum values, across patients and by target tumor. | Posted | Number | 95% Confidence Interval | Within Subj. Coefficient of Variation % | Baseline and retest within 1 to 7 days after (but prior to the start of therapy) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Correlation Between T/Cmax and T/Bmax | Pearson correlation coefficient will be used to quantify the correlation between T/Bmax, the maximum tissue-to-blood ratio activity value, and T/Cmax, the tissue-to-cerebellum activite value Since T/Cmax does not requiring blood sampling and is image derived, a high correlation would indicate that T/Cmax could be an advantageous surrogate for T/Bmax. | Posted | Number | correlation coefficient | At baseline |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Correlation Between MRS Markers and MR Imaging Markers of Vascularity as Well as Between MRS Markers and PET Markers of Tumor Hypoxia | Correlation between MRS markers and MR imaging markers and PET markers of tumor hypoxia MRS markers include: NAA/Cho, Cho/Cr, Lac/Cr, and Lac/NAA measured within tumor and at the periphery. MR imaging markers of vascularity include: CBV, CBF, and ktrans PET tumor hypoxia marker: SUVmax | Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac) | Posted | Number | correlation coefficient | baseline |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Overall and Progression Free Survival | Disease progression was defined by Macdonald criteria. Survival and Progression were evaluated every 3months and at the end of study (up to 5 years) and time to event evaluated. | Posted | Median | 95% Confidence Interval | days | Baseline, every 3 months through study completion (up to 5 years for progression and survivorship) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | SUVpeak and T/Bmax as Measures of Tumor Hypoxia | The FMISO image data were normalized by the average blood activity to produce pixel level tissue-to-blood ratio (T/B) values for all image slices. And the severity of the hypoxia was determined by the pixel with the maximum T/B value (TBmax). FMISO SUVpeak was determined as the average SUV from a 1 cm circular ROI centered over the hottest pixel. Since FMISO selectively binds to hypoxic tissues, SUVpeak within a region provides a measure of tumor hypoxia. | Posted | Mean | Standard Deviation | ratio | baseline |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Hypoxic Volume as a Measure of Tumor Hypoxia | The hypoxic volume (HV) was determined as the volume of pixels in the tumor on in the FMISO\PET with a tumor to blood activity ratio ≥ 1.2. HV is a measure of the spatial extent of tumor hypoxia (in milliliters) | Posted | Mean | Standard Deviation | milliliters | baseline |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | DWI Apparent Diffusion Coefficient (ADC) | Apparent Diffusion Coefficient (ADC) measures water diffusion through tissue (mm^2/s). Cerebral infarction leads to diffusion restriction resulting in a low ADC signal in the infarcted area. A double Gaussian mixed model was fit to the ADC histogram and the mean of the lower and the mean of the higher ADC curves were evaluated | Participants having a usable FMISO\PET and DWI\MRI scans | Posted | Mean | Standard Deviation | mm^2/s | baseline |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Normalized Relative Cerebral Blood Volume (nRCBV) and Normalized Cerebral Blood Flow (nCBF) | Relative cerebral blood volume (RCBV) maps, computed from the integral of ∆R2*(t), were corrected for leakage effects and normalized to normal appearing white matter (nRCBV); nRCBV provides a measure of tumor vasculature Cerebral blood flow (CBF) maps were was normalized to the mean of the region of interest (ROI) in normal appearing white matter (nCBF); nCBF provides a measure of vascular permeability and perfusion | Evaluable participants with both usable FMISO\PET and DSC\MRI. | Posted | Mean | Standard Deviation | ratio | baseline |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Summary of Mean and Median Ktrans Across Participants. | ktrans is a measure of vascular permeability and reflects the rate of gadolinium moves from plasma to extravascular extracellular space (predominantly though blood flow and capillary leakage), which can be represented by the mean or median rate. Mean & Median ktrans within subject were computed using a matrix-based linearization method to fit tissue ∆R1(t) to the extended Tofts model. The mean across subjects is presented below (Mean (Mean-ktrans) and Mean(Median-Ktrans)) | Evaluable patients with usable FMISO\PET and DCE\MRI | Posted | Mean | Standard Deviation | 1/min | baseline |
|
|
until 24hrs after FMISO administration, evaluated up to 72hours post FMISO injection.
The adverse reporting period is 10 half-lives after the administration of the investigational imaging radiotracer, with a minimum reporting period of at least 24hours post injection. Participants must be reassessed for events between 24 and 72hours post injection.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Evaluable Cases | Patients with Newly diagnosed GBM scheduled to have FMISO PET/CT two weeks before initiation of chemoradiotherapy with temozolomide. | 0 | 42 | 0 | 42 | 0 | 42 |
| EG001 | Diagnostic PET (Using FMISO) | Patients with Newly diagnosed GBM who have FMISO PET/CT Imaging two weeks before initiation of chemoradiotherapy with temozolomide. | 0 | 38 | 0 | 38 | 0 | 38 |
| EG002 | Diagnostic MRI (DCE MRI) | Patients with Newly diagnosed GBM who have FMISO PET/CT and Dynamic Contrast Enhanced (DCE) MR Imaging two weeks before initiation of chemoradiotherapy with temozolomide. | 0 | 37 | 0 | 37 | 0 | 37 |
| EG003 | Diagnostic MRI (DSE MRI) | Patients with Newly diagnosed GBM who have FMISO PET/CT and Dynamic Susceptibility Contrast Enhanced (DSC) MR Imaging two weeks before initiation of chemoradiotherapy with temozolomide. | 0 | 31 | 0 | 31 | 0 | 31 |
| EG004 | Diagnostic MRI (DWI MRI) | Patients with Newly diagnosed GBM who have FMISO PET/CT and Diffusion-Weighted Imaging (DWI) MR Imaging two weeks before initiation of chemoradiotherapy with temozolomide. | 0 | 39 | 0 | 39 | 0 | 39 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Donna Harfeil, Director of Protocol Management | ACRIN | 215-717-2765 | dhartfeil@acr.org |
| Dec 18, 2018 |
| Prot_SAP_ICF_000.pdf |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C031843 | fluoromisonidazole |
| D009682 | Magnetic Resonance Spectroscopy |
| D014965 | X-Rays |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D060733 | Electromagnetic Radiation |
| D055590 | Electromagnetic Phenomena |
| D060328 | Magnetic Phenomena |
| D055585 | Physical Phenomena |
| D011827 | Radiation |
| D011839 | Radiation, Ionizing |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OS-1 Death |
|
T/Bmax is the pixel in the tumor region with the maximum tumor:blood ratio (T/Bmax) and T/Bmax depicts the magnitude of the hypoxia TBmax was modeled with a univariate Cox regression model for OS time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. The study was designed to enroll 46 evaluable participants to detect a log hazard ratio of 1.279 for TBmax with HV as a covariate with a 50% event rate |
| Regression, Cox |
| 0.50 |
| Hazard Ratio (HR) |
| 1.16 |
| 2-Sided |
| 95 |
| .75 |
| 1.81 |
| Other |
| Hypoxia Volume (HV) depicts the volume of tumor that has crossed the threshold for hypoxia. Hypoxic Volume (HV) was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.90 | Hazard Ratio (HR) | 1.00 | 2-Sided | 0.97 | 0.97 | 1.03 | Other |
| ktrans reflects the rate of gadolinium moves from plasma to extravascular extracellular space (predominantly though blood flow and capillary leakage). Mean ktrans were computed using a matrix-based linearization method to fit tissue ∆R1(t) to the extended Tofts model Mean ktrans was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.024 | Hazard Ratio (HR) | 1.17 | 2-Sided | 95 | 1.02 | 1.34 | HR reported per 0.01 increase | Other |
| ktrans reflects the rate of gadolinium moves from plasma to extravascular extracellular space (predominantly though blood flow and capillary leakage). Median ktrans were computed using a matrix-based linearization method to fit tissue ∆R1(t) to the extended Tofts model. Median ktrans was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.045 | Hazard Ratio (HR) | 1.32 | 2-Sided | 95 | 1.01 | 1.72 | HR reported per 0.01 increase | Other |
| Relative cerebral blood volume (RCBV) maps, computed from the integral of ∆R2*(t), were corrected for leakage effects and normalized to normal appearing white matter (nRCBV); nRCBV provides a measure of tumor vasculature and was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.31 | Hazard Ratio (HR) | 1.11 | 2-Sided | 95 | 0.90 | 1.37 | Other |
| cerebral blood flow (CBF) maps were was normalized to the mean of the region of interest (ROI) in normal appearing white matter to produce the nCBF and provide another measure of vascular permeability and perfusion nCBF was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.51 | Hazard Ratio (HR) | 1.07 | 2-Sided | 95 | 0.88 | 1.29 | Other |
| Apparent Diffusion Coefficient (ADC) measures water diffusion through tissue. Cerebral infarction leads to diffusion restriction resulting in a low ADC signal in the infarcted area. A double Gaussian mixed model was fit to the ADC histogram and the mean of the lower ADC curve, was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.9700 | Hazard Ratio (HR) | 1.00 | 2-Sided | 95 | 0.79 | 1.26 | Other |
| Apparent Diffusion Coefficient (ADC) measures water diffusion through tissue. Cerebral infarction leads to diffusion restriction resulting in a low ADC signal in the infarcted area. A double Gaussian mixed model was fit to the ADC histogram and the mean of the higher ADC curve, was modeled with a univariate Cox regression model for overall survival (OS) time. The hazard ratio, along with its 95% confidence interval and the p-value based on Wald's statistic are reported. | Regression, Cox | 0.9007 | Hazard Ratio (HR) | 0.99 | 2-Sided | 95 | 0.91 | 1.09 | Other |
| OG002 |
| DSC MRI |
Quantitative DSC measurements: Normalized rCBV [Relative cerebral blood volume] Normalized rCBF[Relative cerebral blood flow] |
| OG003 | DCE MRI | Quantitative DCE measurements Mean vascular permeability (ktrans) Median Ktrans |
| OG004 | DWI-MRI | Apparent diffusion coefficient (ADC) Low and High |
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| OG003 | SUV Max | 17 participants with measured MRS markers and SUVmax: standardized uptake value |
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