Diseases and Abnormalities at or Before Birth

All Conditions

Symptoms and General Pathology

Neoplasms

Rare Diseases

Congenital Abnormalities

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Anti-Infective Agents

Cardiotonic Agents

Amino Acids

Fluorides

Fluorodeoxyglucose F18

Deoxyglucose

Dihydroxyphenylalanine

Radiopharmaceuticals

Antimetabolites

Antiviral Agents

Dopamine

Dopamine Agents

Neurotransmitter Agents

Phenylalanine

Study subjects will receive 18FDG via an IV before undergoing one PET/CT scan over 60 minutes. They will then receive an IV injection of Gadovist for contrast before undergoing a multiparametric MRI scan. Subjects will also receive (18)F-FDOPA via an IV before undergoing another PET/CT scan over 60 minutes.

Positron Emission Tomography

Computed Tomography

Multiparametric Magnetic Resonance Imaging Scan

IV (intravenous) administration of radiotracer

Fludeoxyglucose F-18

fluorine F 18 fluorodopa

Bijoy Kundu, PhD

Florence Yan

The purpose of this pilot study will be to conduct a clinical trial using a time-of-flight PET scanner and MRI scanner to test an improved method for differentiating tumor recurrence from radiation necrosis in glioblastoma patients. We will attempt to do so by performing a static and dynamic FDG-PET scan, a static and dynamic FDOPA-PET scan, and a multiparametric MRI scan - then comparing the results with surgical pathology and static FDG-PET scans. We hypothesize that the new quantitative kinetic analytical methods using FDOPA in combination with FDG will provide crucial functional information to distinguish recurrent tumors from treatment-induced radiation changes in patients with treated brain neoplasms. This is important for improving patient outcomes by allowing treating physicians to more accurately tailor treatments. Furthermore, dynamic FDG and FDOPA PET will be combined with high resolution anatomic and physiologic MRI in order to develop a multimodal multiparametric approach for differentiating tumor recurrence from treatment effect.

PRIMARY OBJECTIVES:

I. The primary objective will be to evaluate the diagnostic accuracy of Dynamic PET imaging in differentiating tumor recurrence from treatment effect (radiation necrosis or pseudoprogression) in patients previously treated with chemo-radiation therapy for primary high grade gliomas. This will be accomplished by examining the concordance between the Dynamic PET imaging prediction and the criterion standard, which will be based on either surgical pathology or an integrated clinical/MRI determination within a 3-6 month interval after Dynamic PET imaging.

SECONDARY OBJECTIVES:

I. The diagnostic accuracy of Static PET imaging, advanced MRI, and advanced MRI + Dynamic PET imaging in differentiating tumor recurrence from radiation-induced necrosis in high grade glioma patients will be examined in the same exact way as just outlined for Dynamic PET imaging.

OUTLINE:

Subjects receive 18FDG (first scan) and (18)F-FDOPA (2-14 days from the first scan) intravenously (IV) slowly over a period of 15-20 seconds and then undergo dynamic PET scans over a period of 60-90 minutes. CT scans on the subjects are performed before the dynamic PET scans for 5 minutes. Subjects also undergo MRI brain examinations just prior to the FDOPA scan over a period of 1 hour, which includes T1 weighed, T1 weighted contrast enhanced, T2 weighted, Diffusion tensor imaging, MR spectroscopy, and Dynamic susceptibility contrast perfusion weighted (DSC-PWI) imaging.

All 5 study subjects will undergo the same procedures.

FDG and FDOPA PET Demonstration of Functional Brain Abnormalities

Will be derived from PET/CT scan imaging.

Will be derived from MRI brain scan imaging.

Including anatomic assessment based on T1, T2, and contrast enhanced T1 weighted imaging, MR spectroscopy data (choline, creatinine, and N-acetyl acetate peak integrals and ratios), MR perfusion data (relative cerebral blood volume), and diffusion tensor imaging data (apparent diffusion coefficient, fractional anisotropy)

To be compared with the imaging analyses for comparing ability to differentiate tumor recurrence from radiation necrosis.

University of Virginia

Antineoplastic Agents

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

Diffusion Weighted Imaging

Fluorine F 18 Fluorodopa

Intensity-Modulated Radiation Therapy

Perfusion Magnetic Resonance Imaging

Quality-of-Life Assessment

Nadia N. Laack, M.D.

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.

PRIMARY OBJECTIVES:

I. 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:

I. 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.

II. 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.

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

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

V. 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.

VI. 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.

VII. 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:

I. 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.

II. 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.

III. 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.

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

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

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

VII. 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.

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

Evaluating the Impact of 18F-DOPA-PET on Radiotherapy Planning for Newly Diagnosed Gliomas

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.

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

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.

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

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.

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

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.

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.

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

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

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.

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.

Mayo Clinic

Diagnostic (PET, pMRI, DTI, IMRT, Temozolomide)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Anaplastic astrocytoma (grade-III glioma) is a mid-grade tumor \& diffusely infiltrating neoplasm demonstrating focal or dispersed anaplasia cells \& an increased growth index compared with grade I \& II astrocytoma. Pathological diagnosis is based on appearance of cells (nuclear atypia) \& growth rate (mitotic activity).

Glioblastoma (Grade-IV glioma) is the highest grade glioma tumor \& is the most malignant form of astrocytoma. The histologic features include: presence of necrosis (dead cells), increase of abnormal growth of blood vessels around the tumor, tumors are always rapidly growing.

Histologic grade of primary tumor

MGMT : O6-methylguanine-DNA methyltransferase methylation status

PET : Positron-emission tomography

pMRI : parallel magnetic resonance imaging

DTI : Diffusion Tensor Imaging

IMRT : Intensity-modulated radiation therapy

MGMT

Nadia N. Laack, MD

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.

Proportion of Grade IV MGMT Un-methylated Patients That Experience Confirmed-progression-free Survival at 6 Months (CPFS6)

Overall Survival

Progression Free Survival

Quality of Life Evaluated With the MD Anderson Symptom Inventory Brain Tumor Module and Mini-Mental Status Exam Questionnaires

Rate of Acute Treatment-related Toxicities Graded Using Common Terminology Criteria for Adverse Events Version 4.0

Rate of Late Treatment-related Toxicities Using the Radiation Therapy Oncology Group/European Organization for Research and the Treatment of Cancer Toxicity Criteria

Inter-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation

Intra-observer Variability With or Without the Addition of 18F-DOPA Positron Emission Tomography Uptake for Radiotherapy Target Volume Delineation

Magnetic Resonance Imaging-only Defined Volumes and the Volumes Defined With the Combination of Magnetic Resonance and Positron Emission Tomography Planning

Patterns of Failure After Radiation Therapy Targeting Volumes by 18F-DOPA Positron Emission Tomography and Conventional Magnetic Resonance Imaging

Predictive Capabilities of 18F-DOPA Positron Emission Tomography, Perfusion Magnetic Resonance Imaging, and Diffusion Tensor Imaging for Localization of Recurrences

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

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

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

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

Overall Study

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Protective Agents

Within 1 week of biopsy or resection, patients undergo 18F-DOPA PET/CT scan and pMRI and DTI at baseline. Patients then undergo stereotactic craniotomy or image-guided biopsy.

Biopsy

Laboratory Biomarker Analysis

Therapeutic Conventional Surgery

Nadia Laack

This pilot clinical trial studies fluorine F 18 fluorodopa (18F-DOPA)-positron emission tomography (PET) in planning surgery in patients with gliomas. New imaging procedures, such as 18F-DOPA-PET scan, may help find gliomas and may help in planning surgery.

PRIMARY OBJECTIVES:

I. Accurately define a standardized 18F-DOPA PET tumor/normal tissue (T/N) threshold to delineate high grade gliomas (HGG) from low grade gliomas (LGG).

SECONDARY OBJECTIVES:

I. Determine correlation between 18F-DOPA PET activity, magnetic resonance imaging (MRI) contrast enhancement and high- or low-grade glioma biopsies.

II. Compare grade from maximum 18F-DOPA uptake samples for all resection patients against the final diagnostic grade, based on the highest grade component from all stereotactic and non-stereotactic samples acquired for open resection patients.

III. Compare volume differences between 18F-DOPA PET activity, MRI contrast enhancement, perfusion MRI (pMRI), and diffusion tensor imaging (DTI) for neurosurgical planning.

IV. Assess the time to progression for patients receiving resections and biopsies only.

TERTIARY OBJECTIVES:

I. Compare histopathology correlations with 18F-DOPA PET against correlations with perfusion MR imaging for accurate identification of the highest grade/highest density disease.

II. Compare histopathology correlations with 18F-DOPA PET against correlations with diffusion tensor imaging information for accurate identification of tumor extent.

III. Compare neurosurgical resection extent volume delineation with and without 18F-FDOPA-PET metabolic imaging information to determine role of metabolic imaging in neurosurgical resection planning.

OUTLINE:

Within 1 week of biopsy or resection, patients undergo 18F-DOPA PET/computed tomography (CT) scan and pMRI and DTI at baseline. Patients then undergo stereotactic craniotomy or image-guided biopsy.

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

18F-DOPA-PET in Planning Surgery in Patients With Gliomas

Evaluating the Impact of 18F-DOPA-PET on Neurosurgical Planning for Gliomas

Paired t-test statistical analysis will be used to evaluate differences in volumes identified using biopsy-validated thresholds as highly aggressive disease comparing 18F-DOPA uptake and relative cerebral blood volume from pMRI.

Paired t-test statistical analysis will be used to evaluate differences in volumes identified using biopsy-validated thresholds as disease extent comparing 18F-DOPA PET and diffusion maps from DTI.

Paired t-test analysis will be performed to determine the level of statistical significance between conventional MRI only and PET + MRI volumes.

To determine the optimal PET threshold for distinguishing HGG from LGG brain tissue, receiver operating characteristic (ROC) analysis and the Youden's index (sum of the sensitivity and specificity - 1) will be used. The Youden's index will be calculated for each possible T/N threshold. The final ROC area under the curve (AUC) value and confidence intervals will be estimated using ROC analysis methods for clustered continuous data as described by Obychowski.

Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between volumes.

The relationship between these T/N values, MRI contrast enhancement values, and the histologic grade of the specimen (HGG, LGG, or non-malignant brain tissue) will be determined using multivariate linear regression. These models will also include as appropriate the specimen cellularity and necrosis values.

Associated confidence intervals will be estimated based on dividing the number of patients whose samples agree by the total number of patients.

National Cancer Institute (NCI)

Patients will receive 18FDOPA-PET for radiation treatment planning

Radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor

Nadia N Laack

This proposal is for a pilot study comparing volumes of 18F-DOPA-PET avidity with contrast enhancement and T2 FLAIR on MRI. Investigators then plan to compare patterns of failure with target volumes, pre-treatment MRI changes and pre-treatment 18F-DOPA-PET.

The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma

MC167B: Pilot Study Investigating the Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma

measured by reviewing 18F-DOPA-PET and conventional MRI with historical controls

Overall survival from initial diagnosis: Time from initial diagnosis to death from any cause censoring patients alive at their last follow-up, assessed up to 2 years from date of randomization

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site:(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm)

Measured by change from baseline to 3 month evaluation in MDA-BFI global fatigue score. Brief fatigue index is a QOL questionnaire with scores ranging from 0, no fatigue, to 10, as bad as you can imagine.

Count of patients that receive re-operation post re-irradiation

QOL will be evaluated using the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) and fatigue will be evaluated using the MD Anderson Brief Fatigue Inventory.Measured by change from baseline to 3 month evaluation in MDASI-BT overall symptom distress score. Scores may range from 0 to 10, with 0 being 'Not present' and 10 being 'As bad as imaginable'.

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site:

(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm)

Patients will receive 18FDOPA-PET for radiation treatment planning. Fluorine F 18 Fluorodopa: Contrast used in PET. Intensity-Modulated Radiation Therapy: Radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Positron Emission Tomography: imaging test

18F-DOPA PET

Ethnicity (NIH/OMB)

Nadia N. Laack, MD, MS

Proportion of Participants With Progression-free Survival

Toxicity, Rate of Grade 3 or Higher Treatment Related to Toxicities

All patients that entered a baseline and at 3 months.

Quality of Life Brief Fatigue Index (BFI) Change From Baseline

Re-operative Count

All treated patients that had available data at baseline and during end of treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FDG and FDOPA PET Demonstration of Functional Brain Abnormalities	NCT04315584	Glioblastoma	Positron Emissi... Computed Tomogr... Multiparametric... Fludeoxyglucose... fluorine F 18 f...	18 Years -	University of Virginia
18F-DOPA-PET in Finding Tumors in Patients With Newly Diagnosed Gliomas Undergoing Radiation Therapy	NCT01991977	Malignant Gliom...	Diffusion Weigh... Fluorine F 18 F... Intensity-Modul... Perfusion Magne... Positron Emissi... Quality-of-Life... Temozolomide	18 Years -	Mayo Clinic
18F-DOPA-PET in Planning Surgery in Patients With Gliomas	NCT02020720	Malignant Gliom... Recurrent Brain...	Biopsy Computed Tomogr... Diffusion Weigh... Fluorine F 18 F... Laboratory Biom... Perfusion Magne... Positron Emissi... Therapeutic Con...	7 Years -	Mayo Clinic
The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma	NCT03242824	Glioma	Fluorine F 18 F... Intensity-Modul... Positron Emissi...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for fluorine f 18 fluorodopa