18F-DOPA-PET in Finding Tumors in Patients With Newly Diagnosed Gliomas Undergoing Radiation Therapy

• Sponsor: Mayo Clinic (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01991977
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 91
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 120.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This phase II trial studies how well fluorine F 18 fluorodopa (18F-DOPA)-positron emission tomography (PET) works in finding tumors in patients with newly diagnosed gliomas undergoing radiation therapy. Comparing results of diagnostic procedures done before and during radiation therapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma	Procedure: Diffusion Weighted Imaging; Drug: Fluorine F 18 Fluorodopa; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Perfusion Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Drug: Temozolomide	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Compare confirmed-progression free survival at 6 months for grade IV MGMT unmethylated glioma patients after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional magnetic resonance (MR) image information with historical controls from Mayo Clinic Rochester patients, including those treated on North Central Cancer Treatment Group (NCCTG) clinical trials.

SECONDARY OBJECTIVES:

1. Compare progression free survival at 12 months for grade III patients after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional MR image information with historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

2. Compare patient overall survival after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional MR image information with historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

3. Evaluate quality of life after radiotherapy treatment targeting dose escalated volumes defined to include high 18F-DOPA PET uptake.

4. Determine acute and late effect toxicity after radiotherapy treatment targeting dose escalated volumes defined to include high 18F-DOPA PET uptake.

5. Compare confirmed-progression free survival at 12 months for grade IV MGMT methylated patients after radiation therapy targeting volumes designed with both 18F-DOPA PET and conventional MR image information with historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

6. Compare confirmed-progression free survival in grade IV MGMT un-methylated patients with similar historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

7. Compare confirmed-progression free survival in grade IV MGMT methylated patients with similar historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

TERTIARY OBJECTIVES:

1. Compare radiation therapy (RT) treatment volumes defined by MR only with RT treatment volumes defined with both PET and MR information for grade IV glioma patients.

2. Compare timing of accurate identification of progression defined by 18F-DOPA PET, perfusion magnetic resonance imaging (pMRI) and conventional MRI for grade IV glioma patients.

3. Compare patterns of failure after radiation therapy targeting volumes defined with target volumes designed to with both 18F-DOPA PET and conventional MR image information with patterns of failure for historical controls from Mayo Clinic Rochester patients, including those on NCCTG clinical trials.

4. Compare RT treatment volumes defined by MR only with RT treatment volumes defined with both PET and MR information for grade III glioma patients.

5. Evaluate intra- and inter-observer variability with vs. without the addition of 18F-DOPA PET uptake for radiotherapy target volume delineation.

6. Compare timing of accurate identification of progression defined by 18F-DOPA PET, pMRI and conventional MRI for grade III glioma patients.

7. Compare predictive capabilities of 18F-DOPA PET, pMRI and diffusion tensor imaging (DTI) for localization of recurrences for patients treated with 18F-DOPA PET-guided RT dose escalation.

OUTLINE:

Patients undergo 18F DOPA-PET, pMRI, and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo intensity-modulated radiation therapy (IMRT) over 30 fractions and receive temozolomide.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluating the Impact of 18F-DOPA-PET on Radiotherapy Planning for Newly Diagnosed Gliomas
• Actual Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Jul 1, 2019
• Anticipated Study Completion Date: Dec 14, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Diagnostic (PET, pMRI, DTI, IMRT, temozolomide) Patients undergo 18F DOPA-PET, pMRI and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo IMRT over 30 fractions and receive temozolomide.

Procedure: Diffusion Weighted Imaging; Undergo DTI; Other Names: Diffusion Weighted MRI Diffusion-Weighted Magnetic Resonance Imaging Diffusion-Weighted MR Imaging Diffusion-Weighted MRI DWI DWI MRI DWI-MRI MR Diffusion-Weighted Imaging ; Drug: Fluorine F 18 Fluorodopa; Undergo 18F-DOPA-PET; Other Names: 18F-FDOPA ; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy ; Procedure: Perfusion Magnetic Resonance Imaging; Undergo pMRI; Other Names: magnetic resonance perfusion imaging ; Procedure: Positron Emission Tomography; Undergo 18F-DOPA-PET; Other Names: Medical Imaging, Positron Emission Tomography PET PET SCAN Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Drug: Temozolomide; Receive temozolomide; Other Names: CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temodal Temodar Temomedac

Outcome Measures

Primary Outcome Measures

1. Proportion of Grade IV MGMT Un-methylated Patients That Experience Confirmed-progression-free Survival at 6 Months (CPFS6) [Time from registration to the confirmed disease progression, assessed at 6 months]

   The proportion of Grade IV MGMT un-methylated patients that experience confirmed-progression-free survival at 6 months (CPFS6). Progression is defined by any of the following: ≥25% increase in the sum of products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events Any new lesion Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose. Failure to return for evaluation due to death or deteriorating condition Clear progression of non-measurable disease

Secondary Outcome Measures

1. Overall Survival [Time from registration to death due to any cause, assessed up to 5 years]

   The distributions of survival times and comparisons between study patients and historical controls will be estimated using the method of Kaplan-Meier.

2. Progression Free Survival [Time from registration to the earliest date of documenting disease progression, assessed up to 5 years]

   The proportion of successes will be estimated by the number of successes divided by the total number of grade III evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. The distributions of progression free survival times and comparisons between these two groups will be estimated using the method of Kaplan-Meier.

3. Quality of Life Evaluated With the MD Anderson Symptom Inventory Brain Tumor Module and Mini-Mental Status Exam Questionnaires [Up to 5 years]

   Analysis will include change percent from baseline using t-tests and generalized linear models to test for changes at each time point and non-zero slope, respectively.

4. Rate of Acute Treatment-related Toxicities Graded Using Common Terminology Criteria for Adverse Events Version 4.0 [Up to 5 years]

5. Rate of Late Treatment-related Toxicities Using the Radiation Therapy Oncology Group/European Organization for Research and the Treatment of Cancer Toxicity Criteria [Up to 5 years]

Other Outcome Measures

1. Inter-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation [Up to 5 years]

   The concordance correlation coefficient will be used to measure agreement between volumes generated with each method, as well as to evaluate inter-observer variability, where variability associated with magnetic resonance imaging will serve as the standard for comparison.

2. Intra-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation [Up to 5 years]

   The concordance correlation coefficient will be used to measure agreement between volumes generated with each method, as well as to evaluate inter-observer variability, where variability associated with magnetic resonance imaging will serve as the standard for comparison.

3. Magnetic Resonance Imaging-only Defined Volumes and the Volumes Defined With the Combination of Magnetic Resonance and Positron Emission Tomography Planning [Up to 5 years]

   Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information. The analysis of volumes from 72 grade IV patients will have 90% power to detect differences in volumes with an effect size of 0.39 using a paired t-test with a 0.05 two-sided significance level. Alternate metrics for comparison will also be assessed, including spatial overlap, distanc

4. Patterns of Failure After Radiation Therapy Targeting Volumes by 18F-DOPA Positron Emission Tomography and Conventional Magnetic Resonance Imaging [Up to 5 years]

   Chi-square tests of proportions will be used to test for differences in the proportions of patients with central, in-field, marginal, or distant failures between the patients on this study and historical controls.

5. Predictive Capabilities of 18F-DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging, and Diffusion Tensor Imaging for Localization of Recurrences [Up to 5 years]

   Compared by identifying the recurrence volume with each modality and correlating with identification of aggressive disease in the pre-radiation therapy planning images.

6. Radiation Therapy Treatment Volumes Defined by Magnetic Resonance Imaging Only and Defined With Both Positron Emission Tomography and Magnetic Resonance Imaging Information for Grade III Glioma Patients [Up to 5 years]

   Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information.

7. Radiation Therapy Treatment Volumes Defined by Magnetic Resonance Imaging Only or Defined With Both Positron Emission Tomography and Magnetic Resonance Imaging Information for Grade IV Glioma Patients [Up to 5 years]

   Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information. The analysis of volumes from 72 grade IV patients will have 90% power to detect differences in volumes with an effect size of 0.39 using a paired t-test with a 0.05 two-sided significance level. Alternate metrics for comparison will also be assessed, including spatial overlap, distan

8. Timing of Accurate Identification of Progression Defined by 18F- DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging and Conventional Magnetic Resonance Imaging for Grade IV Glioma Patients [Up to 5 years]

   The progression identification timing will be compared by calculating the percentage of time each modality was earlier than conventional magnetic resonance imaging. With a sample size of 72, if the observed percentage earlier than conventional magnetic resonance imaging is 30% for either modality, a two-sided 95% confidence interval for a single proportion using the large sample normal approximation will be +/- 10.6%. Progression identification timing will also be compared using Kaplan-Meier methods and paired t-tests to determine if differences exist between the modalities.

9. Timing of Accurate Identification of Progression Defined by 18F- DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging and Conventional Magnetic Resonance Imaging for Grade III Glioma Patients [Up to 5 years]

   Progression identification timing will be compared using Kaplan-Meier methods and paired t-tests to determine if differences exist between the modalities. An exploratory analysis of diffusion tensor imaging for detecting invasive non-enhancing tumor recurrence will also be performed.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed newly diagnosed grade IV malignant glioma; Note: grade III patients are no longer being enrolled

• Computed tomography (CT) simulation, immobilization, MRI and PET imaging, treatment planning, and all follow-up MRI and PET scans to be performed at Mayo Clinic Rochester; Note: the actual radiation therapy treatments and follow-up other than imaging can be performed at Mayo Clinic Rochester, Northfield, LaCrosse, Mankato, Eau Claire, or Albert Lea

• Provide written informed consent

• Ability to complete questionnaire(s) by themselves or with assistance

Exclusion Criteria:

• Patients diagnosed with anaplastic oligodendroglioma

• Unable to undergo MRI scans with contrast (e.g. cardiac pacemaker, defibrillator, kidney failure)

• Unable to undergo an 18F-DOPA PET scan (e.g. Parkinson's disease, taking anti-dopaminergic, or dopamine agonist medication or less than 6 half-lives from discontinuance of dopamine agonists); NOTE: other potentially interfering drugs consist of: amoxapine, amphetamine, benztropine, bupropion, buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine, phentermine, phenylpropanolamine, selegiline, paroxetine, citalopram, and sertraline; if a patient is on any of these drugs, list which ones on the on-study form

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nadia Laack, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 15, 2018

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01991977
• Other Study ID Numbers: MC1374; NCI-2013-02242; MC1374; P30CA015083
• First Posted: Nov 25, 2013
• Last Update Posted: Jul 19, 2022
• Last Verified: Jul 1, 2022

• Additional relevant MeSH terms: Glioma; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
Arm/Group Description	Patients undergo 18F DOPA-PET, pMRI and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo IMRT over 30 fractions and receive temozolomide.
Period Title: Overall Study
STARTED	91
Received PET Tracer	84
Received IMRT Treatment	79
Evaluable for the Primary Outcome	39
COMPLETED	79
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
Arm/Group Description	Patients undergo 18F DOPA-PET, pMRI and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo IMRT over 30 fractions and receive temozolomide.
Overall Participants	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.9 (11.3)
Sex: Female, Male (Count of Participants)
Female	33 41.8%
Male	46 58.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	79 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Histologic grade of primary tumor (Count of Participants)
Grade 3	4 5.1%
Grade 4	75 94.9%
MGMT (Count of Participants)
Methylated	25 31.6%
Un-Methylated	39 49.4%
NA	15 19%

Outcome Measures

1. Primary Outcome

Title	Proportion of Grade IV MGMT Un-methylated Patients That Experience Confirmed-progression-free Survival at 6 Months (CPFS6)
Description	The proportion of Grade IV MGMT un-methylated patients that experience confirmed-progression-free survival at 6 months (CPFS6). Progression is defined by any of the following: ≥25% increase in the sum of products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events Any new lesion Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose. Failure to return for evaluation due to death or deteriorating condition Clear progression of non-measurable disease
Time Frame	Time from registration to the confirmed disease progression, assessed at 6 months

Outcome Measure Data

Analysis Population Description

All Grade IV MGMT un-methylated patients meeting eligibility criteria who have signed a consent form and who have begun treatment with 18F-DOPA PET image-guided dose escalation RT will be evaluable for the endpoint.

Arm/Group Title	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
Arm/Group Description	Patients undergo 18F DOPA-PET, pMRI and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo IMRT over 30 fractions and receive temozolomide.
Measure Participants	39
Number (95% Confidence Interval) [proportion of participants]	0.795 1%

2. Secondary Outcome

Title	Overall Survival
Description	The distributions of survival times and comparisons between study patients and historical controls will be estimated using the method of Kaplan-Meier.
Time Frame	Time from registration to death due to any cause, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Progression Free Survival
Description	The proportion of successes will be estimated by the number of successes divided by the total number of grade III evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. The distributions of progression free survival times and comparisons between these two groups will be estimated using the method of Kaplan-Meier.
Time Frame	Time from registration to the earliest date of documenting disease progression, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Quality of Life Evaluated With the MD Anderson Symptom Inventory Brain Tumor Module and Mini-Mental Status Exam Questionnaires
Description	Analysis will include change percent from baseline using t-tests and generalized linear models to test for changes at each time point and non-zero slope, respectively.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Rate of Acute Treatment-related Toxicities Graded Using Common Terminology Criteria for Adverse Events Version 4.0
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Rate of Late Treatment-related Toxicities Using the Radiation Therapy Oncology Group/European Organization for Research and the Treatment of Cancer Toxicity Criteria
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Inter-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation
Description	The concordance correlation coefficient will be used to measure agreement between volumes generated with each method, as well as to evaluate inter-observer variability, where variability associated with magnetic resonance imaging will serve as the standard for comparison.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Intra-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation
Description	The concordance correlation coefficient will be used to measure agreement between volumes generated with each method, as well as to evaluate inter-observer variability, where variability associated with magnetic resonance imaging will serve as the standard for comparison.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Magnetic Resonance Imaging-only Defined Volumes and the Volumes Defined With the Combination of Magnetic Resonance and Positron Emission Tomography Planning
Description	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information. The analysis of volumes from 72 grade IV patients will have 90% power to detect differences in volumes with an effect size of 0.39 using a paired t-test with a 0.05 two-sided significance level. Alternate metrics for comparison will also be assessed, including spatial overlap, distanc
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Patterns of Failure After Radiation Therapy Targeting Volumes by 18F-DOPA Positron Emission Tomography and Conventional Magnetic Resonance Imaging
Description	Chi-square tests of proportions will be used to test for differences in the proportions of patients with central, in-field, marginal, or distant failures between the patients on this study and historical controls.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Predictive Capabilities of 18F-DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging, and Diffusion Tensor Imaging for Localization of Recurrences
Description	Compared by identifying the recurrence volume with each modality and correlating with identification of aggressive disease in the pre-radiation therapy planning images.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Radiation Therapy Treatment Volumes Defined by Magnetic Resonance Imaging Only and Defined With Both Positron Emission Tomography and Magnetic Resonance Imaging Information for Grade III Glioma Patients
Description	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Radiation Therapy Treatment Volumes Defined by Magnetic Resonance Imaging Only or Defined With Both Positron Emission Tomography and Magnetic Resonance Imaging Information for Grade IV Glioma Patients
Description	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between treatment volumes defined by magnetic resonance imaging only and treatment volumes defined with both positron emission tomography and magnetic resonance imaging information. The analysis of volumes from 72 grade IV patients will have 90% power to detect differences in volumes with an effect size of 0.39 using a paired t-test with a 0.05 two-sided significance level. Alternate metrics for comparison will also be assessed, including spatial overlap, distan
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	Timing of Accurate Identification of Progression Defined by 18F- DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging and Conventional Magnetic Resonance Imaging for Grade IV Glioma Patients
Description	The progression identification timing will be compared by calculating the percentage of time each modality was earlier than conventional magnetic resonance imaging. With a sample size of 72, if the observed percentage earlier than conventional magnetic resonance imaging is 30% for either modality, a two-sided 95% confidence interval for a single proportion using the large sample normal approximation will be +/- 10.6%. Progression identification timing will also be compared using Kaplan-Meier methods and paired t-tests to determine if differences exist between the modalities.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Other Pre-specified Outcome

Title	Timing of Accurate Identification of Progression Defined by 18F- DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging and Conventional Magnetic Resonance Imaging for Grade III Glioma Patients
Description	Progression identification timing will be compared using Kaplan-Meier methods and paired t-tests to determine if differences exist between the modalities. An exploratory analysis of diffusion tensor imaging for detecting invasive non-enhancing tumor recurrence will also be performed.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 5 years
Arm/Group Title	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
Arm/Group Description	Patients undergo 18F DOPA-PET, pMRI and DTI within 14 days before radiation therapy, 3-6 weeks after radiation therapy, and during follow-up. Patients also undergo IMRT over 30 fractions and receive temozolomide.
All Cause Mortality
	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
	Affected / at Risk (%)	# Events
Total	56/84 (66.7%)
Serious Adverse Events
	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
	Affected / at Risk (%)	# Events
Total	3/84 (3.6%)
General disorders
Fatigue	2/84 (2.4%)	2
Infections and infestations
Sepsis	1/84 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)
	Affected / at Risk (%)	# Events
Total	82/84 (97.6%)
Blood and lymphatic system disorders
Anemia	2/84 (2.4%)	2
Blood and lymph sys disorders - Oth Spec	2/84 (2.4%)	2
Febrile neutropenia	2/84 (2.4%)	2
Cardiac disorders
Atrial flutter	1/84 (1.2%)	1
Cardiac disorders - Other, specify	1/84 (1.2%)	2
Ear and labyrinth disorders
Ear and labyrinth disorders - Oth spec	1/84 (1.2%)	1
Hearing impaired	1/84 (1.2%)	2
Endocrine disorders
Endocrine disorders - Other, specify	2/84 (2.4%)	2
Eye disorders
Blurred vision	3/84 (3.6%)	4
Eye disorders - Other, specify	2/84 (2.4%)	2
Optic nerve disorder	1/84 (1.2%)	2
Gastrointestinal disorders
Anal fistula	1/84 (1.2%)	1
Constipation	2/84 (2.4%)	2
Diarrhea	1/84 (1.2%)	1
Fecal incontinence	1/84 (1.2%)	1
Mucositis oral	1/84 (1.2%)	1
Nausea	5/84 (6%)	5
Vomiting	1/84 (1.2%)	1
General disorders
Edema limbs	2/84 (2.4%)	5
Fatigue	81/84 (96.4%)	329
Fever	1/84 (1.2%)	1
Gait disturbance	1/84 (1.2%)	1
Localized edema	1/84 (1.2%)	1
Malaise	1/84 (1.2%)	1
Pain	3/84 (3.6%)	3
Infections and infestations
Infections and infestations - Oth spec	1/84 (1.2%)	1
Peripheral nerve infection	2/84 (2.4%)	4
Upper respiratory infection	1/84 (1.2%)	1
Injury, poisoning and procedural complications
Dermatitis radiation	4/84 (4.8%)	4
Investigations
Platelet count decreased	3/84 (3.6%)	3
Weight loss	1/84 (1.2%)	1
Metabolism and nutrition disorders
Anorexia	2/84 (2.4%)	3
Dehydration	1/84 (1.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/84 (1.2%)	1
Back pain	1/84 (1.2%)	1
Generalized muscle weakness	2/84 (2.4%)	2
Muscle weakness lower limb	6/84 (7.1%)	7
Muscle weakness upper limb	4/84 (4.8%)	4
Musculoskeletal, conn tissue - Oth spec	1/84 (1.2%)	1
Nervous system disorders
Ataxia	3/84 (3.6%)	5
Central nervous system necrosis	28/84 (33.3%)	81
Cognitive disturbance	9/84 (10.7%)	14
Concentration impairment	2/84 (2.4%)	2
Dizziness	1/84 (1.2%)	1
Dysarthria	4/84 (4.8%)	6
Dysphasia	5/84 (6%)	5
Facial muscle weakness	1/84 (1.2%)	1
Headache	12/84 (14.3%)	14
Intracranial hemorrhage	1/84 (1.2%)	1
Memory impairment	5/84 (6%)	7
Muscle weakness left-sided	6/84 (7.1%)	9
Muscle weakness right-sided	4/84 (4.8%)	5
Nervous system disorders - Oth spec	10/84 (11.9%)	19
Neuralgia	1/84 (1.2%)	1
Presyncope	1/84 (1.2%)	1
Seizure	9/84 (10.7%)	11
Somnolence	1/84 (1.2%)	1
Stroke	1/84 (1.2%)	1
Psychiatric disorders
Confusion	1/84 (1.2%)	1
Depression	2/84 (2.4%)	2
Insomnia	1/84 (1.2%)	2
Psychiatric disorders - Other, specify	2/84 (2.4%)	2
Suicidal ideation	1/84 (1.2%)	1
Renal and urinary disorders
Urinary incontinence	2/84 (2.4%)	2
Skin and subcutaneous tissue disorders
Alopecia	18/84 (21.4%)	21
Erythema multiforme	1/84 (1.2%)	1
Rash maculo-papular	3/84 (3.6%)	3
Vascular disorders
Hypertension	2/84 (2.4%)	2
Hypotension	1/84 (1.2%)	1
Thromboembolic event	2/84 (2.4%)	2

Limitations/Caveats

[Not Specified]

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.