Image-Based Quantitative Assessment of Acute Radiation-Induced Changes in Glioma

The overall goal of this study is to determine if quantitative imaging techniques can be used to detect dynamic changes of morphology and different physiologic properties of the tumor during and after completion of radiation treatment and to predict site and time of radiation.

Study Overview

• Status: Terminated
• Conditions: Glioma
• Intervention / Treatment: Radiation: Fractionated Radiation; Drug: Temozolomide; Device: MRI

Detailed Description

Once eligibility criteria have been assessed and the informed consent is obtained, participants will undergo a screening process to further ensure eligibility. Screening prior to registration will comprise a review of pathology reports, postoperative magnetic resonance Imaging (MRI) images, operative reports, and medical history; general physical and neurologic exams; routine blood work; and urine pregnancy test for women of childbearing age.

The study is intended to evaluate the response of radiation treatment (RT). The consent process will be performed between the surgery and the start of RT. RT will be prescribed as per the discretion of the treating radiation oncologist as per the University of Alabama at Birmingham Department of Radiation Oncology treatment protocol in combination with temozolomide.

MRIs will be obtained before start of RT, after completion of 20 +/- 4 Gy. after completion of 40+/- 4 Gy and after the entire radiation treatment. Conventional MRIs including perfusion sequences and whole brain spectroscopy will be performed as a part of the research study. The data obtained from this research studies will not be used for clinical management.

Volumes of the enhancing component, non enhancing component, choline/N-acetyl aspartate (Cho/NAA) will be measure before, during and after RT as described before. Cerebral blood volume (CBV) of the tumor will also be calculated from perfusion imaging at each time point. Apparent diffusion co-efficient (ADC) of the tumor will be calculated from the diffusion imaging.

All the patients will be followed up with imaging and will be treated as per the standard of care. Patients will return for clinical evaluation and standard of care imaging approximately 4 weeks from the completion of the radiation therapy. After that, all the patients will be treated with standard of care maintenance temozolomide therapy and will return every 2-3 months for clinical evaluation and standard of care imaging.

At the time of recurrence, the recurrence site will be assessed and will be compared with the imaging parameters obtained during radiation treatment. Time to recurrence will also be calculated and will be correlated with the imaging parameters.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Newly diagnosed glioma, based on pathology confirmation;
2. At least 8 cm3 of residual enhancing tumor after surgery or significant visible tumor (As seen on immediate postoperative scan);
3. Scheduled to receive standard fractionated RT with concomitant temozolomide therapy;
4. Karnofsky Performance Score > 60.

Exclusion Criteria:

1. Scheduled to receive investigational chemotherapy, immunotherapy, or any other investigational agents;
2. Placement of GLIADEL® wafer in the resection cavity;
3. Significant amount of hemorrhage within the resection cavity (seen on immediate post-operative scan);
4. A large peritumoral infraction related to surgery (identified by new confluent diffusion restriction);
5. Not suitable to undergo MRI or use the MRI contrast agent (GFR<30 mL/min/1.73 m2); or the patient has known anaphylactic reaction to gadolinium based contrast agents.
6. Presence of serious systemic illness, including: uncontrolled infection, uncontrolled malignancy, significant renal disease, or psychiatric/social situations, which might impact the survival endpoint of the study or limit compliance with study requirements.

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: Chemoradiation with MRI assessment; This study has only one arm. The eligible subjects will receive standard of care fractionated radiation therapy along with concomitant temozolomide, which will NOT be changed based on the MRI scans obtained as a part of this study. There is no control or sham group.

Radiation: Fractionated Radiation; Standard of care fractionated radiation therapy will be given to the tumor.; Drug: Temozolomide; Standard of care temozolomide will be given along with radiation therapy; Other Names: Temodar; Device: MRI; Four MRI scan will be performed according to the protocol. The first one will be obtained before start of radiation therapy, the second MRI will be obtained after completion of 20 +/- 4 Gy, the third MRI will be obtained after completion of 40 +/- 4 Gy, and the final MRI will be obtained after completion of the radiation therapy.; Other Names: Multi parametric MRI including MR spectroscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With the Changes of the Chemical Environment of the Tumor	Multiple MRI techniques will be used to assess chemical environment (Cho/NAA) of the tumor during the course of fractionated radiation treatment.	From Baseline to 6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Tumor Cellularity	Diffusion MRI will be used for assessment of measures tumor cellularity (with minimum apparent diffusion co-efficent, ADC) during the course of fractionated radiation treatment.	From baseline to 6 weeks
Changes of Tumor Volume	MRI will be used for assessment of measures tumor volume.	From baseline Up to 6 weeks
Changes of Tumor Angiogenesis	Perfusion MRI will be used for assessment of tumor angiogenesis (with median normalized cerbral blood volume, nCBV) during the course of fractionated radiation treatment.	From baseline to 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression	Percentage change of the Cho/NAA, ADC and nCBV from baseline to the end of radiation therapy, RT will be used for assessment of time to progression.	From Baseline through 24 months.

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Asim Bag, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2016
• Primary Completion (Actual): June 12, 2018
• Study Completion (Actual): June 12, 2018

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: F160324004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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