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

• ClinicalTrials.gov Identifier: NCT03115333
• Recruitment Status: Recruiting
• First Posted: April 14, 2017
• Last Update Posted: June 23, 2023
• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Tracking Information

• First Submitted Date: April 10, 2017
• First Posted Date: April 14, 2017
• Last Update Posted Date: June 23, 2023
• Actual Study Start Date: July 25, 2017
• Estimated Primary Completion Date: May 7, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2017)

• Change in rCBV within enhancing tumor [ Time Frame: Baseline 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.
• OS [ Time Frame: Up 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 10, 2017)

• CBF [ Time Frame: Baseline ]
  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 CBF [ Time Frame: Baseline 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.
• PFS [ Time Frame: Up 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
• rCBV [ Time Frame: Baseline ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DSC-MRI in Measuring rCBV for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma
• Official Title: Change in Relative Cerebral Blood Volume as a Biomarker for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Gliosarcoma
• Recurrent Glioblastoma

Intervention

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

Study Arms

Experimental: Diagnostic (DSC-MRI)

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

Intervention: Diagnostic Test: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 16, 2021): 146
• Original Estimated Enrollment (submitted: April 10, 2017): 165
• Estimated Study Completion Date: May 7, 2027
• Estimated Primary Completion Date: May 7, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03115333
• Other Study ID Numbers: EAF151; NCI-2016-01357 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); EAF151 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); EAF151 ( Other Identifier: CTEP ); U10CA180820 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
• Original Responsible Party: Same as current
• Current Study Sponsor: ECOG-ACRIN Cancer Research Group
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jerrold Boxerman; ECOG-ACRIN Cancer Research Group

• PRS Account: Eastern Cooperative Oncology Group
• Verification Date: June 2023