Glioma
Conditions
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.
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.
Interventions
RADIATIONFractionated Radiation
Standard of care fractionated radiation therapy will be given to the tumor.
DRUGTemozolomide
Standard of care temozolomide will be given along with radiation therapy
DEVICEMRI
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.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
One arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Changes of Tumor Volume | From baseline Up to 6 weeks | MRI will be used for assessment of measures tumor volume. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
Subject #2: Voluntary withdrawal. Subject #5: Voluntary withdrawal.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Chemoradiation With MRI Assessment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 62.8 years |
| Glioblastoma Diagnosis | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
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.
Time frame: From Baseline to 6 weeks.
Population: 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.
Comparison: The baseline and the end of therapy MRI parameters are compared.
Secondary
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.
Time frame: From baseline to 6 weeks
Population: Results of only 2 subjects was included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chemoradiation With MRI Assessment | Changes of Tumor Angiogenesis | baseline | 3.78 mL/100 gm of brain tissue |
| Chemoradiation With MRI Assessment | Changes of Tumor Angiogenesis | Early in therapy (At 2 weeks in therapy) | 3.35 mL/100 gm of brain tissue |
| Chemoradiation With MRI Assessment | Changes of Tumor Angiogenesis | Late therapy (At 4 weeks in therapy) | 1.58 mL/100 gm of brain tissue |
| Chemoradiation With MRI Assessment | Changes of Tumor Angiogenesis | At completion (At 6 weeks from baseline) | 1.2 mL/100 gm of brain tissue |
Secondary
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.
Time frame: From baseline to 6 weeks
Population: Only 3 subjects completed the treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chemoradiation With MRI Assessment | Changes of Tumor Cellularity | Baseline | 0.000675 mm^2/sec |
| Chemoradiation With MRI Assessment | Changes of Tumor Cellularity | Early in therapy (At 2 weeks in therapy) | 0.000798 mm^2/sec |
| Chemoradiation With MRI Assessment | Changes of Tumor Cellularity | Late therapy (At 4 weeks in therapy) | 0.000842 mm^2/sec |
| Chemoradiation With MRI Assessment | Changes of Tumor Cellularity | At completion (At 6 weeks from baseline) | 0.001144 mm^2/sec |
Secondary
Changes of Tumor Volume
MRI will be used for assessment of measures tumor volume.
Time frame: From baseline Up to 6 weeks
Population: Measurements performed only in 2 subjects .
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chemoradiation With MRI Assessment | Changes of Tumor Volume | Baseline | 6.1 cm3 |
| Chemoradiation With MRI Assessment | Changes of Tumor Volume | Early in therapy (At 2 weeks in therapy) | 3.79 cm3 |
| Chemoradiation With MRI Assessment | Changes of Tumor Volume | Late therapy (At 4 weeks in therapy) | 2.66 cm3 |
| Chemoradiation With MRI Assessment | Changes of Tumor Volume | At completion (At 6 weeks from baseline) | 2.16 cm3 |
Other Pre-specified
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.
Time frame: From Baseline through 24 months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chemoradiation With MRI Assessment | Time to Progression | 465 days |