Clinical trial NCT00756106: MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma
Official title: Quantitative Assessment of the Early and Late Effects of Radiation and Chemotherapy on Glioblastoma Using Multiple MRI Techniques
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
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
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-09-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Detailed description: OBJECTIVES:

Primary

* To quantitatively compare the relative cerebral blood volume/flow, mean transit time, and mean vessel diameter as measured by perfusion-weighted MRI before, during, and after chemoradiotherapy in patients with newly diagnosed glioblastoma multiforme.
* To measure the permeability-surface area product on a voxel-by-voxel basis before, during, and after chemoradiotherapy in these patients.
* To measure the full water self-diffusion tensor on a voxel-by-voxel basis before, during, and after chemoradiotherapy in these patients.
* To compare the tensor fractional anisotropy before, during, and after chemoradiotherapy in these patients.
* To compare the 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.
* To test the 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.

Secondary

* To collect blood and urine samples for correlation analysis between imaging changes, molecular markers (including genetic markers), and clinical outcome of glioblastoma multiforme (phenotypic information).
* To correlate blood and urine biomarkers and blood genetic markers with tumor expression of these markers.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Relative Cerebral Blood Volume as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: Relative Cerebral Blood Flow as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: Vessel Diameter as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: Mean Transit Time as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: Permeability-surface Area Product Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: Apparent Diffusion Coefficient Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: 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
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
measure: 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
timeFrame: Baseline, weekly during treatment, monthly following treatment for up to six months
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Elizabeth Gerstner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.