Malignant Central Nervous System Neoplasm, Metastatic Malignant Neoplasm in the Central Nervous System
Conditions
Brief summary
This early phase I trial studies how well hyperpolarized carbon C 13 pyruvate magnetic resonance imaging works in detecting lactate and bicarbonate in participants with central nervous system tumors. Hyperpolarized carbon C 13 pyruvate magnetic resonance imaging may be used to measure the metabolic state of malignant brain tumors.
Detailed description
PRIMARY OBJECTIVES: I. To assess the safety of intravenous (IV) injection of hyperpolarized carbon C 13 pyruvate (hyperpolarized \[1-13C\] pyruvate) for magnetic resonance imaging (MRI). II. To assess the frequency and sensitivity with which lactate and bicarbonate signals can be detected in malignant brain tumors after IV injection of hyperpolarized \[1-13C\] pyruvate. OUTLINE: Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo magnetic resonance spectroscopic imaging (MRSI) over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director). After completion of study, participants are followed up periodically.
Interventions
OTHERGadolinium
gadolinium enhanced MRI
Given IV
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDUREMagnetic Resonance Spectroscopic Imaging
Undergo MRSI
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Daniel M. Spielman
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a known diagnosis of central nervous system (CNS) malignancy, including metastases, with known enhancement on magnetic resonance (MR) who are otherwise eligible to undergo MRI * Glomerular filtration rate (GFR) \> 30 ml/min * No allergy to gadolinium * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Refusal to have an IV placed for injection * Acute major illness (e.g., unstable angina, etc.) or other condition that makes participation unsafe, per the investigator?s judgement * Total bilirubin \> 1.5 x upper limit of normal (ULN) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2.5 x ULN * Gamma-glutamyltransferase (GGT) \> 2.5 x ULN * Pregnant or breast-feeding * Cardiovascular risk, including: * Poorly controlled hypertension, defined as either systolic \> 170 or diastolic \> 110 * Congestive heart failure * Myocardial infarction within the past year * QT prolongation, defined as pretreatment corrected QT interval (QTc) \> 440 msec in males or \> 460 msec in females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 2 or Higher Toxicities | 2 days (+/-2) after the scan | The measurement of this drug is the number of participants with Grade 2 or higher related adverse events (except for asymptomatic lab increases) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Lactate and Bicarbonate Production in Tumor and Normal Brain Tissue | Imaging timepoint (up to 15 minutes to obtain scan) | The outcome is defined as the number of participants with hyperpolarized carbon C 13 pyruvate magnetic resonance signal detection above background noise level of both lactate and bicarbonate in all tumors screened. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Participants undergo MRI over 45 minutes at baseline, then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes. | 3 |
| Known CNS Malignancy Participants undergo MRI over 45 minutes at baseline, then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director). | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No scan due to technical issues | 4 | 0 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Known CNS Malignancy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Number of Participants With Grade 2 or Higher Toxicities
The measurement of this drug is the number of participants with Grade 2 or higher related adverse events (except for asymptomatic lab increases)
Time frame: 2 days (+/-2) after the scan
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Volunteers | Number of Participants With Grade 2 or Higher Toxicities | 0 Participants |
| Known CNS Malignancy | Number of Participants With Grade 2 or Higher Toxicities | 0 Participants |
Other Pre-specified
Lactate and Bicarbonate Production in Tumor and Normal Brain Tissue
The outcome is defined as the number of participants with hyperpolarized carbon C 13 pyruvate magnetic resonance signal detection above background noise level of both lactate and bicarbonate in all tumors screened.
Time frame: Imaging timepoint (up to 15 minutes to obtain scan)