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

Phase 2

Active, not recruiting

• Conditions: Malignant Glioma
• Interventions: 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

• Registration Number: NCT01991977
• Lead Sponsor: Mayo Clinic

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.

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-11-18
• Study First Submitted QC: 2013-11-18
• Study First Posted: 2013-11-25
• Study Start: 2013-12
• Primary Completion: 2019-07-01
• Results First Submitted: 2020-03-19
• Results First Submitted QC: 2020-04-01
• Results First Posted: 2020-04-03
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-24
• Last Update Posted: 2024-04-29
• Study Completion: 2024-12-14

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 91

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	Positron Emission Tomography	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.
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	Quality-of-Life Assessment	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.
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	Intensity-Modulated Radiation Therapy	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.
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	Perfusion Magnetic Resonance Imaging	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.
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	Diffusion Weighted Imaging	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.
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	Fluorine F 18 Fluorodopa	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.
Diagnostic (PET, pMRI, DTI, IMRT, temozolomide)	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.

Primary Outcome Measures

Name	Time	Method
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

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

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States