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

Not Applicable
Recruiting
Conditions
Gliosarcoma
Recurrent Glioblastoma
Interventions
Diagnostic Test: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Registration Number
NCT03115333
Lead Sponsor
ECOG-ACRIN Cancer Research Group
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
146
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Diagnostic (DSC-MRI)Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance ImagingPatients undergo DSC-MRI within 3 days before bevacizumab initiation and at day 15.
Primary Outcome Measures
NameTimeMethod
Change in rCBV within enhancing tumorBaseline to 2 weeks

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.

OSUp to 5 years

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

Secondary Outcome Measures
NameTimeMethod
PFSUp to 5 years

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

rCBVBaseline

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.

CBFBaseline

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.

Change in CBFBaseline to 2 weeks

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.

Trial Locations

Locations (58)

USC / Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Maryland Proton Treatment Center

🇺🇸

Baltimore, Maryland, United States

UT Southwestern/Simmons Cancer Center-Dallas

🇺🇸

Dallas, Texas, United States

IU Health Methodist Hospital

🇺🇸

Indianapolis, Indiana, United States

Eden Hospital Medical Center

🇺🇸

Castro Valley, California, United States

Loma Linda University Medical Center

🇺🇸

Loma Linda, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

🇺🇸

Orange, California, United States

VA Palo Alto Health Care System

🇺🇸

Palo Alto, California, United States

Baptist MD Anderson Cancer Center

🇺🇸

Jacksonville, Florida, United States

Boca Raton Regional Hospital

🇺🇸

Boca Raton, Florida, United States

Mayo Clinic in Florida

🇺🇸

Jacksonville, Florida, United States

Emory University Hospital/Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Northside Hospital

🇺🇸

Atlanta, Georgia, United States

Northside Hospital-Forsyth

🇺🇸

Cumming, Georgia, United States

Indiana University/Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Baptist Health Lexington

🇺🇸

Lexington, Kentucky, United States

University of Maryland/Greenebaum Cancer Center

🇺🇸

Baltimore, Maryland, United States

Minnesota Oncology Hematology PA-Maplewood

🇺🇸

Maplewood, Minnesota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

University of Missouri - Ellis Fischel

🇺🇸

Columbia, Missouri, United States

Regions Hospital

🇺🇸

Saint Paul, Minnesota, United States

Minnesota Oncology Hematology PA-Woodbury

🇺🇸

Woodbury, Minnesota, United States

Siteman Cancer Center at West County Hospital

🇺🇸

Creve Coeur, Missouri, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Siteman Cancer Center-South County

🇺🇸

Saint Louis, Missouri, United States

Memorial Sloan Kettering Monmouth

🇺🇸

Middletown, New Jersey, United States

Siteman Cancer Center at Saint Peters Hospital

🇺🇸

Saint Peters, Missouri, United States

University of New Mexico Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Memorial Sloan Kettering Commack

🇺🇸

Commack, New York, United States

Memorial Sloan Kettering Westchester

🇺🇸

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Carolinas Medical Center/Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

University of Cincinnati/Barrett Cancer Center

🇺🇸

Cincinnati, Ohio, United States

Memorial Hermann Texas Medical Center

🇺🇸

Houston, Texas, United States

Froedtert Menomonee Falls Hospital

🇺🇸

Menomonee Falls, Wisconsin, United States

ProHealth Oconomowoc Memorial Hospital

🇺🇸

Oconomowoc, Wisconsin, United States

ProHealth D N Greenwald Center

🇺🇸

Mukwonago, Wisconsin, United States

ProHealth Waukesha Memorial Hospital

🇺🇸

Waukesha, Wisconsin, United States

UW Cancer Center at ProHealth Care

🇺🇸

Waukesha, Wisconsin, United States

Froedtert West Bend Hospital/Kraemer Cancer Center

🇺🇸

West Bend, Wisconsin, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

University Hospital

🇺🇸

San Antonio, Texas, United States

University of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

East Carolina University

🇺🇸

Greenville, North Carolina, United States

Saint Joseph's Hospital and Medical Center

🇺🇸

Phoenix, Arizona, United States

Mayo Clinic Hospital

🇺🇸

Phoenix, Arizona, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Mayo Clinic in Arizona

🇺🇸

Scottsdale, Arizona, United States

Moffitt Cancer Center-International Plaza

🇺🇸

Tampa, Florida, United States

Moffitt Cancer Center - McKinley Campus

🇺🇸

Tampa, Florida, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

UNC Lineberger Comprehensive Cancer Center

🇺🇸

Chapel Hill, North Carolina, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Aurora Saint Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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