Precise DCE-MRI in Diagnosing Participants With Recurrent High Grade Glioma or Melanoma Brain Metastases

Area B: Precise DCE-MRI Assessment of Brain Tumors

Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is a potentially powerful diagnostic tool for the management of brain cancer and other conditions in which the blood-brain barrier is compromised. This trial studies how well precise DCE MRI works in diagnosing participants with high grade glioma that has come back or melanoma that has spread to the brain. The specially-tailored acquisition and reconstruction (STAR) DCE MRI could provide improved assessment of brain tumor status and response to therapy.

Study Overview

• Status: Terminated
• Conditions: Brain Tumor; Metastatic Melanoma; Brain Metastases; Glioma of Brain
• Intervention / Treatment: Device: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Drug: Bevacizumab Injection

Detailed Description

PRIMARY OBJECTIVES:

I. To optimize and technically validate specially-tailored acquisition and reconstruction (STAR) DCE-MRI based on the accuracy and reproducibility of whole-brain tracer-kinetic (TK) parameter maps.

SECONDARY OBJECTIVES:

I. To develop a robust clinical implementation of STAR DCE-MRI. II. To clinically evaluate STAR DCE-MRI in patients with brain tumors.

OUTLINE: Participants are assigned to 1 of 2 cohorts.

COHORT I: Participants with recurrent high-grade glioma undergo STAR DCE-MRI every 2 months, and just prior to and 4-6 weeks after starting bevacizumab treatment. If there is concern for tumor progression (i.e. increased contrast enhancement), more frequent MRI scans will be scheduled.

COHORT II: Participants with melanoma brain metastases undergo STAR DCE-MRI at baseline and 4-6 weeks after therapy. Participants may undergo more frequent MRI if there is concern for tumor progression.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Steven Carrasco; Phone Number: 323-442-7469; Email: Steven.Carrasco@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• COHORT I: Recurrent high-grade glioma (often with thin areas of enhancement) treated with bevacizumab.
• COHORT I: We will include adult patients with histopathologically confirmed high-grade glioma with evidence of tumor progression at baseline MRI who will undergo treatment with an anti-angiogenic agent (bevacizumab) with or without concomitant chemotherapy, and Karnofsky Performance Score > 60%.
• COHORT I: At least 30 days should have elapsed since prior therapy including surgery and temozolomide chemoradiation.
• COHORT I: Satisfactory renal, hepatic, and hematologic function is required.
• COHORT II: Melanoma brain metastases (often small and spread throughout the brain) treated with immunotherapy.
• COHORT II: We will include adult patients with a tissue-proven history of melanoma who have contrast enhancing brain masses who will undergo treatment with immunotherapy with an anti-CTLA-4 or anti-PD-1 approach (e.g. ipilimumab, pembrolizumab, or nivolumab), and Karnofsky Performance Score > 60%.
• COHORT II: At least 30 days should have elapsed since prior therapy including surgery, stereotactic brain irradiation, and corticosteroid use.

Exclusion Criteria:

• COHORT I: Exclusion criteria include treatment with any other anti-cancer treatment, enzyme-inducing antiepileptic agents, anticoagulant treatment, pregnancy, other anti-angiogenesis therapy and prior thrombo-embolic disorders.
• COHORT I: Exclusion criteria will include the standard contraindications for MRI: 1) prior work as a machinist or metal worker, or history of metal being removed from the eyes, 2) cardiac pacemaker or internal pacing wires, 3) non-MRI compatible vena cava filter, vascular aneurysm clip, heart valve, spinal or ventricular shunt, optic implant, neuro-stimulator unit, ocular implant, or intrauterine device, or 4) claustrophobia, or uncontrollable motion disorder.
• COHORT I: Pregnant women, prisoners, and institutionalized individuals will be excluded.
• COHORT II: Exclusion criteria include treatment with any other anti-cancer treatment, and other immunotherapy exclusion criteria.
• COHORT II: Non-cutaneous melanomas will be excluded.
• COHORT II: Exclusion criteria will include the standard contraindications for MRI: 1) prior work as a machinist or metal worker, or history of metal being removed from the eyes, 2) cardiac pacemaker or internal pacing wires, 3) non-MRI compatible vena cava filter, vascular aneurysm clip, heart valve, spinal or ventricular shunt, optic implant, neuro-stimulator unit, ocular implant, or intrauterine device, or 4) claustrophobia, or uncontrollable motion disorder.
• COHORT II: Pregnant women, prisoners, and institutionalized individuals will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort I (STAR DCE-MRI); Participants with recurrent high-grade glioma undergo STAR DCE-MRI every 2 months, and just prior to and 4-6 weeks after starting bevacizumab treatment. Participants may undergo more frequent MRI if there is concern for tumor progression.	Device: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo STAR DCE-MRI; Other Names: DCE-MRI; DCE MRI; DYNAMIC CONTRAST ENHANCED MRI; Drug: Bevacizumab Injection; Bevacizumab will be give to participants who have recurrent high-grade glioma as part of standard of care.; Other Names: Avastin
Experimental: Cohort II (STAR DCE-MRI); Participants with melanoma brain metastases undergo STAR DCE-MRI at baseline and 4-6 weeks after therapy. Participants may undergo more frequent MRI if there is concern for tumor progression.	Device: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo STAR DCE-MRI; Other Names: DCE-MRI; DCE MRI; DYNAMIC CONTRAST ENHANCED MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume transfer constant (Ktrans)	The raw data will be acquired at the voxel level. Then the analytic parameters will be extracted from voxel-wise data such as the mean, median, interquartile range, skewness and kurtosis. Receiver-operating characteristic curves (ROC) will be used to illustrate the univariate prediction accuracy for each parameter in predicting the clinically determined outcome. The pattern of change with different clinical response status will be visually illustrated using spaghetti plots or other graphical approaches. Classification and Regression Tree (CART) with 10-fold cross validation will be used for building the final prediction model and determine the diagnostic cut point(s). CART analysis will also include demographics, comorbidity information, and relevant biological variables including sex. The final model accuracy will be assessed using area under the curve (AUC) when fitting a ROC curve using predicted outcome against the actual outcome.	Up to 3 years
Fractional plasma volume (vp)	The raw data will be acquired at the voxel level. Then the analytic parameters will be extracted from voxel-wise data such as the mean, median, interquartile range, skewness and kurtosis. ROC will be used to illustrate the univariate prediction accuracy for each parameter in predicting the clinically determined outcome. The pattern of change with different clinical response status will be visually illustrated using spaghetti plots or other graphical approaches. CART with 10-fold cross validation will be used for building the final prediction model and determine the diagnostic cut point(s). CART analysis will also include demographics, comorbidity information, and relevant biological variables including sex. The final model accuracy will be assessed using AUC when fitting a ROC curve using predicted outcome against the actual outcome.	Up to 3 years
Fractional extravascular-extracellular space volume (ve)	The raw data will be acquired at the voxel level. Then the analytic parameters will be extracted from voxel-wise data such as the mean, median, interquartile range, skewness and kurtosis. ROC will be used to illustrate the univariate prediction accuracy for each parameter in predicting the clinically determined outcome. The pattern of change with different clinical response status will be visually illustrated using spaghetti plots or other graphical approaches. CART with 10-fold cross validation will be used for building the final prediction model and determine the diagnostic cut point(s). CART analysis will also include demographics, comorbidity information, and relevant biological variables including sex. The final model accuracy will be assessed using AUC when fitting a ROC curve using predicted outcome against the actual outcome.	Up to 3 years
Model-free initial area under the contrast agent concentration curve (iAUC)	The raw data will be acquired at the voxel level. Then the analytic parameters will be extracted from voxel-wise data such as the mean, median, interquartile range, skewness and kurtosis. ROC will be used to illustrate the univariate prediction accuracy for each parameter in predicting the clinically determined outcome. The pattern of change with different clinical response status will be visually illustrated using spaghetti plots or other graphical approaches. CART with 10-fold cross validation will be used for building the final prediction model and determine the diagnostic cut point(s). CART analysis will also include demographics, comorbidity information, and relevant biological variables including sex. The final model accuracy will be assessed using AUC when fitting a ROC curve using predicted outcome against the actual outcome.	Up to 3 years

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Krishna Nayak, PhD, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Actual): November 22, 2023
• Study Completion (Actual): November 22, 2023

Study Registration Dates

• First Submitted: October 1, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasm Metastasis; Glioma; Brain Neoplasms; Melanoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 6B-17-2 (Other Identifier: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2018-01890 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R33CA225400 (U.S. NIH Grant/Contract)

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