Hyperpolarized Imaging in Diagnosing Participants With Glioma

Study Overview
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Brief Summary
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This pilot trial studies the side effects of hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing participants with glioma. Diagnostic procedures, such as hyperpolarized carbon C 13 pyruvate MRI, may help find and diagnose glioma.

Detailed Description
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PRIMARY OBJECTIVES: To assess the safety and feasibility of hyperpolarized 13C MR metabolic imaging as a new and unique tool for evaluating tumor burden and detecting early response to standard therapy in patients with glioma. To define the most appropriate imaging parameters for obtaining hyperpolarized 13C data from the brain, one hundred patients with evidence of residual disease from a prior MRI examination will have hyperpolarized metabolic imaging after receiving one or two injections of hyperpolarized 13 C pyruvate. For subjects who are willing to receive two injections, the 2nd injection will be used to assess reproducibility, evaluate the performance of new acquisition methods, or compare metabolism between [1-13C]pyruvate and [213C]pyruvate. To establish the time course of changes in hyperpolarized pyruvate and lactate peaks on a voxel by voxel basis from the dynamic hyperpolarized data after the injection(s) of hyperpolarized 13C pyruvate. Twenty patients will be studied before and after treatment with standard radiation and temozolomide in order to determine the time course of delivery of 13C pyruvate and the location of maximum pyruvate and lactate or glutamate signals in normal brain and in the region of T2 hyperintensity (T2L). To evaluate if patients who receive treatment with standard radiation and temozolomide exhibit a reduction in hyperpolarized 13C lactate/pyruvate or 13C glutamate/pyruvate at post-radiation follow-up compared to their baseline scan. A second group of twenty patients will be studied at the time determined from the prior group to provide the maximum contrast between lactate/pyruvate or glutamate/pyruvate in the lesion versus normal brain. OUTLINE: Participants are assigned to 1 of 2 cohorts. COHORT I: Patients receive one or two hyperpolarized carbon C 13 pyruvate injections intravenously (IV) and undergo MRI. COHORT II: Patients receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI before standard treatment with radiation therapy and temozolomide and 4 weeks after completion of radiation therapy. After completion of study treatment, participants are followed for up to 24 months.

Official Title
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Pilot Study of Safety and Feasibility of Acquiring Hyperpolarized Imaging in Patients With Gliomas

Conditions
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Glioma

Intervention / Treatment
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* Radiation: Hyperpolarized Carbon C 13 Pyruvate
* Procedure: Magnetic Resonance Imaging
* Radiation: Radiation Therapy
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Patients in Cohort 1: Histologically proven glioma who have evidence of evaluable disease based on a prior magnetic resonance (MR) scan. For Patients in Cohort 2: Histologically proven glioma who will be undergoing standard treatment with radiation and temozolomide. To be included in the study all subjects must also meet the following criteria: Patients must be > 18 years old and with a life expectancy > 12 weeks. Patients must have a Karnofsky performance status of ≥ 60. Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. This tests must be performed within 60 days prior to Hyperpolarized Imaging scan. Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate the imaging examination or any disease that will obscure toxicity or dangerously alter response to the imaging agent. Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure Patients must not have a history of myocardial infarction or unstable angina within 12 months prior to study enrollment. This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate. No exclusion to this study will be based on race. Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information. Patients may not be known to be human immunodeficiency virus (HIV)-positive. HIV testing is not required for study participation. Patients must not have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years. Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of Hyperpolarized Imaging scan. Effective contraception (men and women) must be used in subjects of child-bearing potential. Exclusion Criteria: (1) Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I (hyperpolarized C13, MRI)<br>Patients receive hyperpolarized carbon C 13 pyruvate intravenously IV and undergo MRI. The second hyperpolarized 13 C injection/imaging will be started approximately 15 to 60 minutes after the first injection for those who are willing to receive two 13 C injections | Radiation: Hyperpolarized Carbon C 13 Pyruvate<br>* Given IV<br>* Other names: Hyperpolarized Pyruvate (13C);Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;|
| Experimental: Cohort II (hyperpolarized C13, MRI, radiation, temozolomide)<br>Patients receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI before standard treatment with radiation therapy and temozolomide and 4 weeks after completion of radiation therapy. | Radiation: Hyperpolarized Carbon C 13 Pyruvate<br>* Given IV<br>* Other names: Hyperpolarized Pyruvate (13C);Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Radiation: Radiation Therapy<br>* Undergo radiation therapy<br>* Other names: radiotherapy;Drug: Temozolomide<br> <br> * Other names: Temomedac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Adverse events will be monitored from just before investigational medicinal product (IMP) administration until the end of study participation. Vital signs (blood pressure and heart rate only) will be recorded at baseline and 30 minutes post injection. For blood pressures and heart rate recorded after IMP administration, the following safety endpoints will be summarized for each part of the study: (1) The occurrence of changes from baseline, at each post-administration time point, greater than a pre-specified magnitude (20 mm Hg for systolic blood pressure, 10 mm Hg for diastolic blood pressure, 10 beats per minute for heart rate). (2) The occurrence of post-administration values outside the normal limits. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology (Toxicity) Criteria for Adverse Events (CTCAE) version 4.0 | Up to 24 months | 
| Peak lactate/pyruvate ratio in brain tissue | The lactate/pyruvate ratio and/or glutamate/pyruvate will be compared in tumor versus normal appearing brain tissue. Comparisons will be made using a Wilcoxon signed rank test. | Up to 24 months | 
| Peak lactate/pyruvate ratio in (13C) pyruvate scan | The lactate/pyruvate ratio and/or glutamate/pyruvate from baseline will be compared to the ratio on the post-radiation therapy (RT) repeat scan. Comparisons will be made using a Wilcoxon signed rank test. | Up to 4 months. |