MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma

NCT00756106 | Terminated Results DMC

• 1 other identifier: 07-292
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic ependymoma; adult anaplastic oligodendroglioma; adult mixed glioma

Outcome Measures

Primary Outcomes (9)

• 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

• 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

Study Arms (1)

Temozolomide and Radiation Therapy

EXPERIMENTAL

Drug: temozolomide; Other: Imaging biomarker analysis; Radiation: Photon Radiation Therapy

Interventions

temozolomide DRUG

Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator.

Temozolomide and Radiation Therapy

Imaging biomarker analysis OTHER

MRI

Temozolomide and Radiation Therapy

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.

Temozolomide and Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Newly diagnosed anaplastic glioma (WHO grade III) or glioblastoma multiforme (WHO grade IV) * Measurable disease * Residual tumor size after surgery ≥ 1 cm in one dimension * 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: * Claustrophobia * Metallic objects or implanted medical devices (e.g., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) * Sickle cell disease * Renal failure * High risk for kidney disease (e.g., age \> 60 years, diabetes, or history of systemic lupus erythematosus or multiple myeloma) * 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: * See Disease Characteristics * Non-VEGF investigational agent allowed * No concurrent chemotherapy (other than temozolomide) * No concurrent electron, proton, particle, or implant radiotherapy * No concurrent stereotactic radiosurgery * No concurrent anti-VEGF anti-tumor agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (4)

• 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.

  PMID: 38197800 DERIVED

• 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.

  PMID: 33842889 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.

  PMID: 25113840 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.

  PMID: 24309981 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Astrocytoma; Ependymoma; Oligodendroglioma; Glioma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Elizabeth Gerstner
• Organization: Massachusetts General Hospital

EGERSTNER@mgh.harvard.edu

Study Officials

• Elizabeth Gerstner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 19, 2008
• Study Start: July 1, 2008
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: May 13, 2020
• Results First Posted: April 21, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)