Not provided
Not provided
Not provided
Not provided
Not provided
Funding ended
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
RATIONALE: Diagnostic procedures, such as MRI, may help in learning how well radiation therapy and chemotherapy work in killing tumor cells and allow doctors to plan better treatment.
PURPOSE: This clinical trial is studying MRI scans to see how well they evaluate the effects of radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma multiforme or anaplastic glioma.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients undergo radiotherapy once daily 5 days a week for 6 weeks. Patients also receive oral temozolomide once daily 7 days a week during radiotherapy. After completion of chemoradiotherapy, patients receive oral temozolomide once daily for 5 days. Treatment with temozolomide repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI, including perfusion- and diffusion-weighted MRI, diffusion tensor imaging, and magnetic resonance spectroscopy prior to initiation of chemoradiotherapy, once weekly during chemoradiotherapy, and then monthly until tumor progression or until completion of 6 courses of post chemoradiotherapy.
After completion of study treatment, patients are followed annually.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Temozolomide and Radiation Therapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| temozolomide | Drug | Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Relative Cerebral Blood Volume as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Relative cerebral blood volume (rCBV) is the blood volume in the region of interest (ROI) divided by the blood volume in the symmetrical region on the other side of the normal brain (control region). CBV was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Relative Cerebral Blood Flow as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Relative cerebral blood flow (rCBF) is the blood flow rate (the volume of blood passing through the specified are over a specified period of time) in the region of interest (ROI) divided by the blood flow rate in the symmetrical region on the other side of the normal brain (control region). CBF was assessed using spin-echo post-contrast T1-weighted images. CBF was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Vessel Diameter as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Baseline, weekly during treatment, monthly following treatment for up to six months |
Not provided
Not provided
DISEASE CHARACTERISTICS:
Newly diagnosed anaplastic glioma (WHO grade III) or glioblastoma multiforme (WHO grade IV)
Measurable disease
Planning to undergo standard chemoradiotherapy with temozolomide
PATIENT CHARACTERISTICS:
Glomerular filtration rate ≥ 60 mL/min
Mini Mental Status Exam score > 15
Sufficiently competent to give informed consent
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 2 months after completion of study treatment
No contraindication to MRI or to use of the contrast agent gadolinium, including any of the following:
No known history of chronic obstructive pulmonary disease or emphysema
No other co-existing condition that, in the judgement of the investigator, may increase risk to the patient
PRIOR CONCURRENT THERAPY:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Gerstner, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38197800 | Derived | Hoebel KV, Bridge CP, Ahmed S, Akintola O, Chung C, Huang RY, Johnson JM, Kim A, Ly KI, Chang K, Patel J, Pinho M, Batchelor TT, Rosen BR, Gerstner ER, Kalpathy-Cramer J. Expert-centered Evaluation of Deep Learning Algorithms for Brain Tumor Segmentation. Radiol Artif Intell. 2024 Jan;6(1):e220231. doi: 10.1148/ryai.220231. | |
| 33842889 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Temozolomide and Radiation Therapy | temozolomide: Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator. Imaging biomarker analysis: MRI Photon Radiation Therapy: Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Imaging biomarker analysis | Other | MRI |
|
| Photon Radiation Therapy | Radiation | Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions. |
|
| Mean Transit Time as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Mean transit time (MTT) corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation. | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Permeability-surface Area Product Before, During, and After Chemoradiotherapy | Permeability-surface Area Product (Ktrans). Ktrans reflects the efflux rate of contrast from blood plasma into the tissue extravascular extracellular space (EES). Ktrans was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Apparent Diffusion Coefficient Before, During, and After Chemoradiotherapy | Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue. ADC was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy | Fractional anisotropy (FA) is a measure of the directionality of the molecular motion of water. | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Relative Regional Concentrations of Choline, N-acetyl-asparate, and Myoinositol as Measured by Magnetic Resonance Spectroscopy Before, During, and After Chemoradiotherapy to Interrogate Cell Membrane Turnover, Neuronal Integrity, and Glial Reactions | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Affects of a Short Period of 100% Oxygen Inhalation on Imaging of Tumor and Surrounding Tissue Regions of Interest, Specifically Cerebral Blood Volume Changes in Each Area as Compared to Room Air | Baseline, weekly during treatment, monthly following treatment for up to six months |
| Hoebel KV, Patel JB, Beers AL, Chang K, Singh P, Brown JM, Pinho MC, Batchelor TT, Gerstner ER, Rosen BR, Kalpathy-Cramer J. Radiomics Repeatability Pitfalls in a Scan-Rescan MRI Study of Glioblastoma. Radiol Artif Intell. 2020 Dec 16;3(1):e190199. doi: 10.1148/ryai.2020190199. eCollection 2021 Jan. |
| 25113840 | Derived | Emblem KE, Farrar CT, Gerstner ER, Batchelor TT, Borra RJ, Rosen BR, Sorensen AG, Jain RK. Vessel caliber--a potential MRI biomarker of tumour response in clinical trials. Nat Rev Clin Oncol. 2014 Oct;11(10):566-84. doi: 10.1038/nrclinonc.2014.126. Epub 2014 Aug 12. |
| 24309981 | Derived | Pinho MC, Polaskova P, Kalpathy-Cramer J, Jennings D, Emblem KE, Jain RK, Rosen BR, Wen PY, Sorensen AG, Batchelor TT, Gerstner ER. Low incidence of pseudoprogression by imaging in newly diagnosed glioblastoma patients treated with cediranib in combination with chemoradiation. Oncologist. 2014 Jan;19(1):75-81. doi: 10.1634/theoncologist.2013-0101. Epub 2013 Dec 5. |
| COMPLETED |
|
| NOT COMPLETED |
|
One participant withdrew consent after baseline and was excluded from the analysis set
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Temozolomide and Radiation Therapy | temozolomide: Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator. Imaging biomarker analysis: MRI Photon Radiation Therapy: Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Karnofsky Performance Status | The Karnofsky Performance Status is a measure of patients' general well-being and activities of daily living. The score ranges from 0 to 100, higher scores indicating a patient is better able to carry out daily activities. | Median | Full Range | units on a scale |
|
| 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 | Relative Cerebral Blood Volume as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Relative cerebral blood volume (rCBV) is the blood volume in the region of interest (ROI) divided by the blood volume in the symmetrical region on the other side of the normal brain (control region). CBV was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | One participant withdrew consent after baseline and was excluded from the analysis set. The number of patients evaluated decreased over time due to participants experiencing disease progression and discontinuing from the study | Posted | Mean | Full Range | ratio | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
|
| |||||||||||||||||||||||||||
| Primary | Relative Cerebral Blood Flow as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Relative cerebral blood flow (rCBF) is the blood flow rate (the volume of blood passing through the specified are over a specified period of time) in the region of interest (ROI) divided by the blood flow rate in the symmetrical region on the other side of the normal brain (control region). CBF was assessed using spin-echo post-contrast T1-weighted images. CBF was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | One participant withdrew consent after baseline and was excluded from the analysis set. The number of patients evaluated decreased over time due to participants experiencing disease progression and discontinuing from the study | Posted | Mean | Full Range | ratio | Baseline, weekly during treatment, monthly following treatment for up to six months |
| |||||||||||||||||||||||||||||
| Primary | Vessel Diameter as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Data not collected | Posted | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
| ||||||||||||||||||||||||||||||||
| Primary | Mean Transit Time as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy | Mean transit time (MTT) corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation. | Data not collected | Posted | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
| |||||||||||||||||||||||||||||||
| Primary | Permeability-surface Area Product Before, During, and After Chemoradiotherapy | Permeability-surface Area Product (Ktrans). Ktrans reflects the efflux rate of contrast from blood plasma into the tissue extravascular extracellular space (EES). Ktrans was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | One participant withdrew consent after baseline and was excluded from the analysis set. The number of patients evaluated decreased over time due to participants experiencing disease progression and discontinuing from the study | Posted | Mean | Full Range | min ^-1 | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
| ||||||||||||||||||||||||||||
| Primary | Apparent Diffusion Coefficient Before, During, and After Chemoradiotherapy | Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue. ADC was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide | One participant withdrew consent after baseline and was excluded from the analysis set. The number of patients evaluated decreased over time due to participants experiencing disease progression and discontinuing from the study | Posted | Mean | Full Range | mm2/s | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
| ||||||||||||||||||||||||||||
| Primary | Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy | Fractional anisotropy (FA) is a measure of the directionality of the molecular motion of water. | Data not collected | Posted | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
| |||||||||||||||||||||||||||||||
| Primary | Relative Regional Concentrations of Choline, N-acetyl-asparate, and Myoinositol as Measured by Magnetic Resonance Spectroscopy Before, During, and After Chemoradiotherapy to Interrogate Cell Membrane Turnover, Neuronal Integrity, and Glial Reactions | Data not collected | Posted | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
| ||||||||||||||||||||||||||||||||
| Primary | Affects of a Short Period of 100% Oxygen Inhalation on Imaging of Tumor and Surrounding Tissue Regions of Interest, Specifically Cerebral Blood Volume Changes in Each Area as Compared to Room Air | Data not collected | Posted | Baseline, weekly during treatment, monthly following treatment for up to six months |
|
|
Adverse event data were not collected
Adverse event data were not collected as a part of this study
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 | Temozolomide and Radiation Therapy | temozolomide: Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator. Imaging biomarker analysis: MRI Photon Radiation Therapy: Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions. | 0 | 0 | 0 | 0 | 0 | 0 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elizabeth Gerstner | Massachusetts General Hospital | EGERSTNER@mgh.harvard.edu |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| D001254 | Astrocytoma |
| D004806 | Ependymoma |
| D009837 | Oligodendroglioma |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
|
| Week 1 CRT |
|
|
| Week 2 CRT |
|
|
| Week 3 CRT |
|
|
| Week 4 CRT |
|
|
| Week 5 CRT |
|
|
| Week 6 CRT |
|
|
| Pre-C1 TMZ |
|
|
| Pre-C2 TMZ |
|
|
| Pre-C3 TMZ |
|
|
| Pre-C4 TMZ |
|
|
| Pre-C5 TMZ |
|
|
| Pre-C6 TMZ |
|
|
| Post-TMZ |
|
|
|
|
|
|
|