Neoplasms

All Conditions

Nervous System Diseases

Behaviors and Mental Disorders

Rare Diseases

Glioblastoma

Brain Neoplasms

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

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Quality of Life

Neuroepithelioma

IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.

IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.

IMPT

IMRT

Cognitive tests given at baseline, 4 months, then every 2 months for 2 years.

Cognitive Tests

Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.

Questionnaires

Caroline Chung, MD

The goal of this clinical research study is to compare IMRT with IMPT in patients with glioblastoma. Researchers want to learn about cognitive side effects (mental status changes) that may occur, such as memory loss and impaired thinking.

IMRT is the delivery of focused radiation therapy using photon beams and advanced computer planning to help shape the dose in order to give the highest possible dose to the tumor with the least dose to surrounding normal tissues.

IMPT is also focused radiation therapy similar to IMRT, but it uses proton particles to deliver the radiation instead of photon beams. IMPT also uses advanced computer planning in order to shape the dose to the target with the least dose to surrounding normal tissues.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group.

If you are in Group 1, you will receive IMRT.

If you are in Group 2, you will receive IMPT.

Radiation Therapy:

In both groups, you will receive radiation treatments each day, Monday-Friday, starting on Day 1. You will continue to receive radiation treatment until you have completed 30 total treatments. This is a total of up to 6 weeks of treatment.

You will sign a separate consent form for the IMRT or IMPT that will explain the procedures and risks in detail.

Study Visits:

Before beginning radiation, you will have what is called a "simulation" to plan your radiation. During the simulation, you will be flat on your back on a computed tomography (CT) table and a soft plastic mask will be made to help hold your head still during treatment. This is the position you will be in when you receive radiation treatment. You will then have a CT scan, which will make computerized images to help plan your treatment.

At Month 2 (+/- 30 days):

* You will have a physical exam, including measurement of your vital signs.
* You will have an MRI to check the status of the disease.
* You will be asked about any drugs you may be taking and side effects you may be having.
* You will complete the thinking skills tests and the questionnaires about your quality of life and symptoms.

Length of Treatment:

You may receive up to 6 weeks of radiation therapy. You will no longer be able to receive radiation therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your active participation on the study will be over after the follow-up visits.

Follow-Up:

At Month 4 (+/- 30 days) and then every 2 months for up to 2 years after radiation therapy:

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any side effects you may be having.
* You will have an MRI to check the status of the disease.
* You will complete the thinking skills tests and the questionnaires about your quality of life and symptoms.

Starting 2 years after radiation therapy, the study staff will continue checking your medical record to find out about your health status from then on.

This is an investigational study. IMRT is delivered using FDA-approved and commercially available methods. IMPT is investigational.

Up to 90 participants will be enrolled in this study. All will be enrolled at MD Anderson.

Glioblastoma Multiforme (GBM) Proton vs. Intensity Modulated Radiotherapy (IMRT)

A Prospective Phase II Randomized Trial to Compare Intensity Modulated Proton Radiotherapy (IMPT) vs. Intensity Modulated Radiotherapy (IMRT) for Newly Diagnosed Glioblastoma (WHO Grade IV)

Time to cognitive failure on any of 6 primary variables from pre-specified cognitive tests (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, TMT Part A or Part B, COWA) with failure defined as a decline that meets or exceeds the reliable change index (RCI) for each cognitive test variable. A cumulative incidence approach used to estimate median time to cognitive failure in order to account for the competing risks of disease progression and death.

Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method.

Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Participants last known to be alive and progression-free are censored at date of last contact.

The adverse severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0).

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL

Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL

Grade 4 Life-threatening consequences; urgent intervention indicated.

Count of participants experiencing adverse events. Should a participant experience multiple adverse events at different grades, the patient is counted only once at the highest grade.

M.D. Anderson Cancer Center

During this study, both the Intensity Modulated Radiotherapy (IMRT) and Intensity Modulated Proton Radiotherapy (IMPT) arms reported serious and life-threatening adverse events. Specifically, 2 participants in the IMRT arm and 1 participant in the IMPT arm experienced Grade 4 life-threatening events that required urgent intervention

IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.

IMRT: IMRT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.

Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years.

Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.

Intensity Modulated Radiotherapy (IMRT)

IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.

IMPT: IMPT treatments delivered as once daily fractions, 5 days per week Monday - Friday for 30 treatments.

Cognitive Tests: Cognitive tests given at baseline, 4 months, then every 2 months for 2 years.

Questionnaires: Questionnaires about quality of life and symptoms given at baseline, 4 months, then every 2 months for 2 years.

Intensity Modulated Proton Radiotherapy (IMPT)

Total

Age, Continuous

Sex: Female, Male

White

Hispanic

African American

Asian

Race/Ethnicity, Customized

United States

Region of Enrollment

Between June 2013 and March 2016, 90 patients consented to participate and 67 were treated (28 PT, 39 IMRT) with the majority of patients excluded before treatment began due to insurance denial of proton therapy

Dr. Caroline Chung, MD- VP, Chief Data Officer, Data Impact & Governance

Time to Cognitive Failure

Between June 2013 and March 2016, 90 participants consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.

Overall Survival

Between June 2013 and March 2016, 90 patients consented to participate and 67 (41 and 26 participants effectively treated with IMRT and IMPT) were treated with the majority of participants excluded before treatment began due to insurance denial of proton therapy.

Progression Free Survival (PFS)

Grade 4 Adverse Events

Grade 3 Adverse Events

Grade 2 Adverse Events

Number of Participants Experienced Adverse Events by Maximum Grade (Grade 2 or Higher)

Overall Study

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Breast Neoplasms

Prostatic Neoplasms

Carcinoma

Carcinoma, Hepatocellular

Neuroendocrine Tumors

Neuroendocrine Tumor

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate

Chelating Agents

Adult participants, who were scheduled for repeated enhanced magnetic resonance imaging (MRI), receive a linear gadoliniumbased contrast agent (GBCA, i.e. Eovist/ Primovist, MultiHance or Omniscan) prior to MRI. Each participant will receive the same GBCA throughout the study.

Adult participants, who were scheduled for repeated enhanced magnetic resonance imaging (MRI), receive a macrocyclic gadolinium-based contrast agent (GBCA, i.e. Gadavist/ Gadovist, Dotarem, Magnescope or ProHance) prior to MRI. Each participant will receive the same GBCA throughout the study.

Adult participants who were never exposed to any gadolinium-based contrast agent and matching the population characteristics of the two GBCA arms. They will not receive any gadolinium-based contrast agent over the study course, but may undergo clinically indicated imaging (e.g. unenhanced magnetic resonance imaging (MRI), unenhanced or enhanced computed tomography, ultrasound and/or X-ray).

Motor Tests

The UE-MRI of the brain will be performed at baseline and at the year 5 visit in order to exclude presence of a significant MRI abnormality

Unenhanced-MRI of the brain

Blood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration

Gadolinium Measurements

Administered as defined by the treating physician as part of routine clinical practice

Gadoxetate disodium

Gadobenate dimeglumine

Gadodiamide

Gadoterate meglumine

Gadobutrol

Gadoteridol

Nathalie LE FUR, PhD

Frantz HEBERT

Ronald Korn, MD

Valentine Mildred

Carla Harmath, MD

Teresa Osmulski

Praveen Sudhindra, MD

Mukesh Harisinghani, MD

Fishman Michael, MD

Joseph Yap

Leo Tsai, MD

Ricardo Sanchez, MD

Sara Schiller

Boris Nicolas Bloch, MD

Lauren Burke, MD

Rebecca Jordan

Nabeel SARWANI, MD

Meera Kasireddy

Ryan Lee, MD

Sydney Haldeman Sydney

Takeshi Yokoo, MD

Riya Nellippallil

Khaled Elsayes, MD

Nolan Caroll

Bruce Richard, MD

Patricia Moura

Joilda Batista de Almeida Rego, MD

Keyla Deucher

Cassiano Mateus Forcelini, MD

Brenda Santos

Ivan Pedrollo, MD

Marcela Maria Dutra

Israel Silva Maia, MD

Nicole Rabello

Luis Eduardo Werneck de Carvalho, MD

Luciana Cubas Volpe

Kathia Abdalla

Study Coordinator

Lis Gomes, MD

Gilberto Szarf

Ronaldo Baroni, MD

Samir Chenaf

Sebastien MOLIERE, MD

Alfonso Cerase, MD

Anna Ianza

Alessandra Guglielmi, MD

YoungJi Lee

Dong Joon Kim, MD

Hwasong Lee

Sang Soo Shin, MD

JinSil Choi

Won Chang, MD

Hayun Jung

Hae Woong Jeong, MD

Yun Jung

Jeong Heo, MD

Gyu Won Kim

JuYeon Cho,, MD

so hyun Kim

Joon Jeong, MD

DaJeong Kwon

Chang-hwan Choi, MD

This study is a postmarketing requirement jointly carried out by four NDA holders (Bayer AG, Bracco, GE Healthcare and Guerbet) and the CRO IQVIA.

The study aims to create detailed images of the organs and tissue of the human body during x-ray, CT-scan or MRI investigations, doctors are using contrast media (a kind of dye) which can be given to patients by injection into a blood vessel or by mouth.

In this study researchers want to find out whether so called gadolinium-based contrast agents (GBCAs) have an effect on body movement and mental skills when given to participants multiple times within 5 years.

The study plans to enroll about 2076 participants suffering from a condition for which they are likely to have at least annually a MRI or another imaging examinations. Only adults up to 65 years will be considered to join this study. During the study duration of 5 years participants will receive annually a MRI or other imaging tests (such as CT-scan, x-ray) and will visit the study doctor at least 7 times for physical examinations, laboratory investigations and tests on body movement and mental skills.

The primary objective of the study is to assess the potential effect of repeated exposure to either a linear or a macrocyclic gadolinium-based contrast agent (GBCA) on change from baseline to Year 5 in composite measure of motor and cognitive function among neurologically normal adults in comparison to a matched non-GBCA- exposed control group.

The secondary objectives comprise the assessment of the following endpoints in GBCA-exposed participants as compared to controls a) changes from baseline in composite measure of motor and cognitive function post-baseline on yearly basis (Years 1 to 4); b) changes from baseline in each individual test of motor and cognitive function on yearly basis (Years 1 to 5). Total Gd concentrations in blood and urine samples on yearly basis (Years 1 to 5) and adverse events will be collected as secondary objectives.

Of note : The study is considered interventional because of the addition of UE-MRI scans for all participants, as well as blood sampling and the administration of the motor and cognitive tests. The GBCA administered as part of the contrast-enhanced MR imaging in the experimental arms is not the intervention in this study. Neither the protocol nor the investigators assign patients to a specific GBCA as part of the study, making this part of the study observational rather than interventional. The participants were already scheduled, prior to study screening, to undergo CE-MRI as part of their clinical care. The choice of GBCA for the CE-MRI will be based on medical need and institutional usage of GBCA, independent of study participation.

Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years

Prospective Evaluation of Potential Effects of Repeated Gadolinium-based Contrast Agent (GBCA) Administrations of the Same GBCA on Motor and Cognitive Functions in Neurologically Normal Adults in Comparison to a Non-GBCA Exposed Control Group

The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests

Bayer AG (Sponsor)

Bracco (Sponsor)

GEHC (Sponsor)

Guerbet

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Glioblastoma Multiforme (GBM) Proton vs. Intensity Modulated Radiotherapy (IMRT)	NCT01854554	Brain Cancer	IMPT IMRT Cognitive Tests Questionnaires	18 Years -	M.D. Anderson Cancer Center
Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years	NCT04373564	Motor Function Cognitive Funct... Contrast Media	Motor Tests Cognitive Tests Unenhanced-MRI ... Gadolinium Meas... Gadoxetate diso... Gadobenate dime... Gadodiamide Gadoterate megl... Gadobutrol Gadoteridol	18 Years - 64 Years	Guerbet
Glioblastoma Multiforme (GBM) Proton vs. Intensity Modulated Radiotherapy (IMRT)	NCT01854554	Brain Cancer	IMPT IMRT Cognitive Tests Questionnaires	18 Years -	M.D. Anderson Cancer Center

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