DSC-MRI in Measuring rCBV for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma

Change in Relative Cerebral Blood Volume as a Biomarker for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma

This phase II trial studies how well dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) works in measuring relative cerebral blood volume (rCBV) for early response to bevacizumab in patients with glioblastoma that has come back. DSC-MRI may help evaluate changes in the blood vessels within the cancer to determine a patient?s response to treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Gliosarcoma; Recurrent Glioblastoma
• Intervention / Treatment: Diagnostic test: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether binary changes (increase versus [vs.] decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with overall survival (OS).

SECONDARY OBJECTIVES:

I. To determine whether the baseline pre-treatment rCBV measure alone is associated with OS.

II. To determine whether binary changes (increase vs. decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with progression-free survival (PFS).

III. To determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with OS or PFS.

IV. To determine the association between rCBV and OS when adjusting for the changes in enhancing tumor volume.

V. To determine whether baseline cerebral blood flow (CBF) or change in CBF is associated with OS or PFS.

OUTLINE:

Patients undergo DSC-MRI within 3 days before bevacizumab initiation and at day 15.

After completion of study intervention, patients are followed up every 3 months for 1 year and then every 6 months for up to 4 years.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Phoenix, Arizona, United States, 85013
      • Saint Joseph's Hospital and Medical Center
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • Tampa, Florida, United States, 33607
      • Moffitt Cancer Center-International Plaza
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center - McKinley Campus
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Cumming, Georgia, United States, 30041
      • Northside Hospital-Forsyth
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21201
      • Maryland Proton Treatment Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • East White Plains, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati/Barrett Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Texas Medical Center
    • San Antonio, Texas, United States, 78229
      • University Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Wisconsin
    • Menomonee Falls, Wisconsin, United States, 53051
      • Froedtert Menomonee Falls Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Mukwonago, Wisconsin, United States, 53149
      • ProHealth D N Greenwald Center
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital
    • West Bend, Wisconsin, United States, 53095
      • Froedtert West Bend Hospital/Kraemer Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically proven intracranial glioblastoma or gliosarcoma at initial surgery

  • Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made (high-grade transformation)
• Karnofsky performance status >= 70
• Women must not be pregnant or breast-feeding
• Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to give whole-dose bevacizumab therapeutically, either as single therapy or in conjunction with other chemotherapeutic regimens; patients getting bevacizumab to support additional radiation therapy or immunotherapy, or primarily for reduction of edema rather than for tumor treatment, are excluded; this must be the patient?s initial recurrence
• Patient must not have been treated previously with immunotherapies (vaccines, checkpoint inhibitors, T-cells)
• Intratumoral hemorrhage (acute, subacute, or chronic) as seen on hemosiderin-sensitive (gradient-echo) MRI may preclude patient inclusion because of anticipated limited evaluation due to magnetic susceptibility artifact on the heavily T2-weighted DSC-MRI images; if the region of enhancing tumor not affected by blooming artifact on the hemosiderin-sensitive images does not meet the 10 x 10 x 10 mm ?measurable enhancement? threshold specified elsewhere, the patient is ineligible
• Progressive enhancement (> 25% increase in contrast enhancing volume compared to nadir) on MRI within 14 days of registration, >= 42 days since completion of radiation/temozolomide therapy, and >= 28 days since surgical resection or cytotoxic chemotherapy; measurable enhancement is defined as two perpendicular in-plane diameters of at least 10 mm and at least 10 mm in the 3rd orthogonal direction

• Patients must be able to tolerate brain MRI scans with dynamic intravenous gadolinium-based contrast agent injections

  • Ability to withstand 22 gauge intravenous (IV) placement
  • No history of untreatable claustrophobia
  • No magnetic resonance (MR) incompatible implants/devices or metallic foreign bodies

  • No contraindication to intravenous contrast administration

    • Adequate organ function, including adequate renal function defined as estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73 m^2 as calculated per institution standard of care, and meeting local site requirements for intravenous administration of gadolinium-based MRI contrast agents
  • No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
  • Weight compatible with limits imposed by the MRI scanner table
• Patient must be scheduled to receive treatment with a standard dose regimen of bevacizumab (bevacizumab infusion on days 1 and 15 of a 28-day treatment cycle); patient can be treated with bevacizumab alone or in combination with other chemotherapies Exclusion Criteria: (see Inclusion Criteria)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic (DSC-MRI); Patients undergo DSC-MRI within 3 days before bevacizumab initiation and at day 15.	Diagnostic test: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC-MRI; Other Names: DSC-MRI; Dynamic Susceptibility Contrast-Enhanced MRI; DYNAMIC SUSCEPTIBILITY-CONTRAST MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in rCBV within enhancing tumor	Will determine whether binary changes (increase vs. decrease) in rCBV is associated with OS. Kaplan-Meier survival curves will be generated for both the increased and the decreased rCBV groups. The median survival time of both groups will be estimated and compared with a two-sided log rank test. Univariate Cox proportional hazards model will be used to test the association between changes in rCBV from baseline to 2 weeks and OS or PFS.	Baseline to 2 weeks
OS	Will determine if binary changes (increase vs. decrease) in rCBV is associated with OS. The median survival time of both groups will be estimated and compared with a two-sided log rank test. Will determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with OS. Univariate Cox proportional hazards model will be used to test the association between changes in rCBV from baseline to 2 weeks and OS. The hazard ratio and its 95% confidence interval (CI) will be presented. Will determine the as	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBF	Will determine if baseline CBF is associated with OS or PFS. Kaplan-Meier survival curves will be generated for both the increased and the decreased CBF groups, for either OS or PFS. The median survival time/progression free survival time of both groups will be estimated and compared with a two-sided log rank test. Univariate Cox proportional hazards model will be used to test the association between baseline CBF and OS or PFS. The hazard ratio and its 95% CI will be presented.	Baseline
Change in CBF	Will determine if changes in CBF is associated with OS or PFS. Kaplan-Meier survival curves will be generated for both the increased and the decreased CBF groups, for either OS or PFS. The median survival time/progression free survival time of both groups will be estimated and compared with a two-sided log rank test. The hazard ratio and its 95% CI will be presented.	Baseline to 2 weeks
PFS	Will determine whether binary changes (increase vs. decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with PFS. Will determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with PFS. Univariate Cox proportional hazards model will be used to test the association between changes in rCBV from baseline to 2 weeks and PFS. Kaplan-Meier survival curves will be generated for both the increased and the decreased rCBV grou	Up to 5 years
rCBV	Will determine whether the baseline pre-treatment rCBV measure alone is associated with OS. Univariate Cox proportional hazards model will be used to test the association between baseline rCBV and OS. The hazard ratio and its 95% confidence interval will be presented.	Baseline

Collaborators and Investigators

• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jerrold Boxerman, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2017
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): May 7, 2027

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Resonance Imaging; Perfusion Magnetic Resonance Imaging
• Other Study ID Numbers: EAF151 (Other Identifier: CTEP); U10CA180820 (U.S. NIH Grant/Contract); NCI-2016-01357 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No