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

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03168919
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 20.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Glioma	Radiation: Fractionated Radiation; Drug: Temozolomide; Device: MRI	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: One arm studyOne arm study
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Image-Based Quantitative Assessment of Acute Radiation-Induced Changes in Glioma
• Actual Study Start Date: Oct 6, 2016
• Actual Primary Completion Date: Jun 12, 2018
• Actual Study Completion Date: Jun 12, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With the Changes of the Chemical Environment of the Tumor [From Baseline to 6 weeks.]

   Multiple MRI techniques will be used to assess chemical environment (Cho/NAA) of the tumor during the course of fractionated radiation treatment.

Secondary Outcome Measures

1. Changes of Tumor Cellularity [From baseline to 6 weeks]

   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.

2. Changes of Tumor Volume [From baseline Up to 6 weeks]

   MRI will be used for assessment of measures tumor volume.

3. Changes of Tumor Angiogenesis [From baseline to 6 weeks]

   Perfusion MRI will be used for assessment of tumor angiogenesis (with median normalized cerbral blood volume, nCBV) during the course of fractionated radiation treatment.

Other Outcome Measures

1. Time to Progression [From Baseline through 24 months.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 14, 2016

More Information

Publications

None provided.

• Responsible Party: Asim Bag, Associate Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03168919
• Other Study ID Numbers: F160324004
• First Posted: May 30, 2017
• Last Update Posted: Oct 1, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Glioma; Temozolomide

Study Results

Participant Flow

Recruitment Details	Recruitment period: 10/2016 through 3/2018 Location: The subjects were identified from the hospital during the admission for resection of the tumor. They were recruited from the clinic of the radiation oncologists and/or neurosurgeons.
Pre-assignment Detail	Subject #2: Voluntary withdrawal. Subject #5: Voluntary withdrawal.

Arm/Group Title	Chemoradiation With MRI Assessment
Arm/Group Description	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. Fractionated Radiation: Standard of care fractionated radiation therapy will be given to the tumor. Temozolomide: Standard of care temozolomide will be given along with radiation therapy 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.
Period Title: Overall Study
STARTED	5
COMPLETED	3
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Chemoradiation With MRI Assessment
Arm/Group Description	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. Fractionated Radiation: Standard of care fractionated radiation therapy will be given to the tumor. Temozolomide: Standard of care temozolomide will be given along with radiation therapy 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.
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 60%
>=65 years	2 40%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62.8
Sex: Female, Male (Count of Participants)
Female	1 20%
Male	4 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 20%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%
Glioblastoma Diagnosis (Count of Participants)
Count of Participants [Participants]	5 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The number of participants dropped from 5 to 3 because 2 participants withdrew from the study. The chemical evaluation could not be evaluated due to poor quality imaging.

Arm/Group Title	Chemoradiation With MRI Assessment
Arm/Group Description	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. Fractionated Radiation: Standard of care fractionated radiation therapy will be given to the tumor. Temozolomide: Standard of care temozolomide will be given along with radiation therapy 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.
Measure Participants	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiation With MRI Assessment
	Comments	The baseline and the end of therapy MRI parameters are compared.
	Type of Statistical Test	Other
	Comments	Comparison
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Due to very small accrual, the statistical analysis couln't be performed.

2. Secondary Outcome

Title	Changes of Tumor Cellularity
Description	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.
Time Frame	From baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

Only 3 subjects completed the treatment.

Arm/Group Title	Chemoradiation Arm
Arm/Group Description	Diffuion MRI was performed before, during and after completion of radiation
Measure Participants	3
Baseline	0.000675
Early in therapy (At 2 weeks in therapy)	0.000798
Late therapy (At 4 weeks in therapy)	0.000842
At completion (At 6 weeks from baseline)	0.001144

3. Secondary Outcome

Title	Changes of Tumor Volume
Description	MRI will be used for assessment of measures tumor volume.
Time Frame	From baseline Up to 6 weeks

Outcome Measure Data

Analysis Population Description

Measurements performed only in 2 subjects .

Arm/Group Title	Chemoradiation Arm
Arm/Group Description	Volumetric MRI was performed before, during and after completion of radiation
Measure Participants	2
Baseline	6.1
Early in therapy (At 2 weeks in therapy)	3.79
Late therapy (At 4 weeks in therapy)	2.66
At completion (At 6 weeks from baseline)	2.16

4. Secondary Outcome

Title	Changes of Tumor Angiogenesis
Description	Perfusion MRI will be used for assessment of tumor angiogenesis (with median normalized cerbral blood volume, nCBV) during the course of fractionated radiation treatment.
Time Frame	From baseline to 6 weeks

Outcome Measure Data

Analysis Population Description

Results of only 2 subjects was included.

Arm/Group Title	Chemoradiation Arm
Arm/Group Description	Perfusion MRI was performed before, during and after completion of radiation
Measure Participants	2
baseline	3.78
Early in therapy (At 2 weeks in therapy)	3.35
Late therapy (At 4 weeks in therapy)	1.58
At completion (At 6 weeks from baseline)	1.2

5. Other Pre-specified Outcome

Title	Time to Progression
Description	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.
Time Frame	From Baseline through 24 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemoradiation Arm
Arm/Group Description	Only 3 subjects were imaged
Measure Participants	3
Mean (Full Range) [days]	465

Adverse Events

Time Frame	1 year 6 months
Arm/Group Title	Chemoradiation With MRI Assessment
Arm/Group Description	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. Fractionated Radiation: Standard of care fractionated radiation therapy will be given to the tumor. Temozolomide: Standard of care temozolomide will be given along with radiation therapy 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.
All Cause Mortality
	Chemoradiation With MRI Assessment
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Chemoradiation With MRI Assessment
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Chemoradiation With MRI Assessment
	Affected / at Risk (%)	# Events
Total	0/5 (0%)

Limitations/Caveats

The study enrollment was much less than anticipated. With only 5 subjects in the study, it is difficult to make a meaningful conclusion.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.