18F-DOPA-PET/MRI Scan in Imaging Elderly Patients With Newly Diagnosed Grade IV Malignant Glioma or Glioblastoma During Planning for a Short Course of Proton Beam Radiation Therapy

Glioblastoma Clinical Trial

Official title:

Phase II Study of Short Course Hypofractionated Proton Beam Therapy Incorporating 18F-DOPA-PET/MRI for Elderly Patients With Newly Diagnosed Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03778294
• Other study ID #: MC1774
• Secondary ID: NCI-2018-02800MC
• Status: Completed
• Phase: Phase 2
• Start date: March 28, 2019
• Est. completion date: November 26, 2023

Study information

• Verified date: December 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well fluorodopa F 18-positron emission tomography/magnetic resonance imaging scan (18F-DOPA-PET/MRI) works in imaging elderly patients with newly diagnosed grade IV malignant glioma or glioblastoma during planning for a short course of proton beam radiation therapy. 18F-DOPA is a chemical tracer that highlights certain cells during imaging. PET scan, is a metabolic imaging technique which takes advantage of how tumor cells take up nutrients differently than normal tissue. MRI scans are used to guide radiation therapy for most brain tumors. Hypofractionated proton beam therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Using 18FDOPA-PET scans along with MRI scans may be able to provide the radiation doctor with information on tumor tissue versus normal, healthy tissue and may help the doctor more accurately plan the radiation treatment.

Description:

PRIMARY OBJECTIVE:

I. Compare overall survival at 12 months for grade IV glioma patients after radiation therapy targeting volumes designed with both 18F-DOPA-PET and conventional magnetic resonance (MR) image (or PET/computed tomography [CT]) information with historical controls.

SECONDARY OBJECTIVES:

I. Compare progression free survival at 12 months after radiation therapy targeting volumes designed with both 18F-DOPA-PET and conventional MR image information with historical controls.

II. Determine acute and late effect toxicity after hypofractionated proton beam radiotherapy treatment including areas of high 18F-DOPA-PET uptake (T/N > 2.0).

CORRELATIVE RESEARCH OBJECTIVES:

I. Compare radiotherapy (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 differences in RT volumes identified using biopsy-validated thresholds as highly aggressive disease comparing 18F-DOPA uptake and relative cerebral blood volume (relCBV) from perfusion MRI (pMRI) as well as differences in RT volumes identified using biopsy-validated thresholds as tumor extent comparing 18F-DOPA uptake and diffusion maps from diffusion tensor imaging (DTI) will be evaluated.

III. Evaluate quality of life after radiotherapy using European Organization for Research and Treatment of Cancer (EORTC) questionnaires compared with historical controls from Keim-Guibert et al.

IV. Compare differences in proton radiation planning utilizing radiobiologic modeling/evaluation techniques performed at Mayo Clinic Rochester to linear energy transfer distribution evaluation at Mayo Clinic Arizona.

OUTLINE:

Patients receive 18F-DOPA intravenously (IV) and undergo PET/MRI or PET/CT imaging scan. Patients then receive proton beam radiotherapy over 5 or 10 consecutive days excluding weekend and standard of care temozolomide on days 1-7 or 1-14. Beginning cycles 2, patients receive standard of care temozolomide on days 1-5. Cycles with temozolomide repeat every 28 days for up to 7 cycles in the in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, and then periodically for up to 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: November 26, 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed newly diagnosed grade IV malignant glioma

• Planned radiation treatments at Mayo Clinic Arizona or Mayo Clinic Rochester

• Willing to sign release of information for any radiation and/or follow-up records

• Provide informed written consent

• Patients with estimated glomerular filtration rate (eGFR) >= 60 mg/min/1.72 m^2

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

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2

Exclusion Criteria:

• Patients diagnosed with grades I-III glioma

• Currently on Avastin at time of treatment

• 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: amoxapine, amphetamine, benztropine, buproprion, 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

• Pregnant women, nursing women, or men or women of childbearing potential who are unwilling to employ adequate contraception.

• NOTE: All women enrolled in this study will be age 65 or over, and at the determination of the principal investigator (PI), will not be of childbearing potential. If the radiology department requires a pregnancy test before administering the 18FDOPA injection, they may perform one per their standard of care

Related Conditions & MeSH terms

• Glioblastoma
• Glioma
• Malignant Glioma

Intervention

Procedure:
• Computed Tomography
Undergo PET/CT

Other:
• Fluorodopa F 18
Given IV

Procedure:
• Magnetic Resonance Imaging
Undergo PET/MRI
• Positron Emission Tomography
Undergo PET/CT or PET/MRI

Radiation:
• Proton Beam Radiation Therapy
Receive proton beam RT

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Drug:
• Temozolomide
Drug

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Radiotherapy (RT) Treatment Volumes	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 (MR) only and treatment volumes defined with both positron emission tomography (PET) and MR information.	Up to 5 years post treatment
Other	Quality of Life (QOL)	QOL surveys will be compared to data from historical controls. Quality of life will be assessed at baseline and at each magnetic resonance imaging (MRI) evaluation (up to 6 evaluations). QOL will be measured using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30.	Up to 5 years post treatment
Other	Differences in Proton Radiation Planning	Paired t-test statistical analysis will be performed to determine if any differences exist and the level of statistical significance between proton plan metrics based off the two modeling/evaluation techniques.	Up to 5 years post treatment
Primary	Overall Survival (OS)	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated utilizing exact binomial methodology. The distribution of survival time will be estimated using the method of Kaplan-Meier (1958).	Time from registration to death due to any cause, assessed up to 12 months
Secondary	Progression Free Survival	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated utilizing exact binomial methodology.	At 12 months after radiation therapy
Secondary	Progression Free Survival	The distribution of progression free survival times groups will be estimated using the method of Kaplan-Meier (1958).	Time from registration to the earliest date documenting disease progression, assessed up to 5 years
Secondary	Incidence of Adverse Events (AEs)	The rate of acute and late treatment-related toxicities for newly diagnosed high-grade glioma patients treated with fluorodopa F 18-positron emission tomography (18F-DOPA PET) image-guided hypofractionated proton beam therapy will be determined, with acute radiotherapy (RT) toxicities graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 5 years post treatment