Brain Imaging Biomarkers in Patients With Brain Metastasis

Imaging Trial of Biomarkers to Guide Individualized Therapy in Patients With Brain Metastasis Receiving Radiotherapy

A biomarker is a measurable indicator of the severity or presence of some disease state. In this study, brain metastases patients who will be receiving radiation treatment, will undergo CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) scans prior to and after radiation treatment to measure these biomarkers. This is a single-center phase II study to validate the predictive abilities of biomarkers, in terms of determining how patients will respond to radiation treatment.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases, Adult
• Intervention / Treatment: Diagnostic test: CT and MRI Scans

Detailed Description

Advances in medical imaging can provide useful information to guide and look at the response to treatment. Previous studies suggest early changes in the tumor after radiation treatment may be detectable using special MRI (Magnetic Resonance Imaging), and CT (Computed Tomography) scans. A biomarker is a measureable indicator of the severity or presence of some disease state. Previous studies suggest that the change in several imaging biomarkers can predict who will respond to radiation treatment. In this study, patients will undergo CT and MRI scans prior to and after radiation treatment to measure these biomarkers. The purpose of this study is to validate the predictive abilities of biomarkers in terms of determining how patients will respond to radiation treatment. This is a single-center phase II study, which will be conducted at the Princess Margaret Cancer Center. The study will be enrolling up to a total of 90 patients who will be receiving radiation treatment for brain metastases. Patients will be asked to participate within this study for 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Shultz, M.D., Ph. D; Phone Number: 416-946-6899; Email: david.shultz@rmp.uhn.on.ca
• Study Contact Backup: Name: Catherine Coolens, Ph. D; Phone Number: 416-946-5011; Email: catherine.coolens@rmp.uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, L4W4C2
      • Recruiting
      • University Health Network
      • Contact: David Shultz, MD; Phone Number: 416 946 4501; Email: david.shultz@rmp.uhn.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Biopsy proven primary malignancy (original biopsy is adequate as long as the brain imaging is consistent with brain metastases)
• At least one index lesion with diameter > 1cm and without imaging evidence of hemorrhage
• Patients age > 18 years of age
• Patients planned for RT to brain metastases
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Previous Whole Brain Radiotherapy
• Previous radiosurgery to the index lesion
• Individuals unable to undergo contrasted MRI for whatever reason

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

Other: CT and MRI Scans; Each patient will undergo a 3T MRI scan as well as a dynamic contrast-enhanced CT scan within one week prior to the start of treatment. Patients will also undergo a research 3T MRI scan and research dynamic contrast-enhanced CT scan at the one week post radiotherapy mark. An MRI scan during their 3 month post-treatment follow up visits will take place as per routine standard of care.

Diagnostic test: CT and MRI Scans; CT and MRI scans will occur before and after radiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Assessment in Neuro-Oncology (RANO) to validate biomarkers	Using RANO to validate imaging predictive biomarkers of response to radiotherapy	Up to 2 years.
Response Evaluation Criteria in Solid Tumors (RECIST) criteria to validate biomarkers	Using RECIST criteria to validate imaging predictive biomarkers of response to radiotherapy	Up to 2 years.
Progression Free Survival (PFS) to validate biomarkers	Using PFS to validate imaging predictive biomarkers of response to radiotherapy	Up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective (Radiological) Progression	Defined as increase in volume of contrast uptake on MRI of > 25% as measured by two perpendicular tumor diameters compared to the smallest measurement ever for the same lesion by the same technique.	Up to 2 years.
Objective (Radiological) Response	Defined as stable or reduced volume of contrast uptake on MRI (i.e., all non-progression).	Up to 2 years.
Time to Intracranial Local Progression	Defined as the time interval between the date of first treatment and the date of objective radiological progression of any one of the treated lesions.	Up to 2 years.
Time to Intracranial Distant Progression	Defined as the time interval between the date of first treatment and the date of new brain metastases, with or without progression of the treated lesions.	Up to 2 years.
Brain Progression Free Survival	Defined as the time interval between the date of first treatment and the date of disease progression in the brain or death due to disease in the brain, whichever comes first.	Up to 2 years.
Unexpected and/or Serious Toxicities (AEs)	AEs that are deemed by the PI to be possibly, probably or definitely attributable to the research MRI and/or CT will be reported according to CTCAE version 4.3.	Up to 2 years.

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Catherine Coolens, Ph. D, Princess Margaret Cancer Center - UHN

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Radiotherapy; Biomarkers; Radiation Therapy; Computed Tomography; Radiosurgery
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 18-5380

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No