A Phase I Study: PET Imaging of Cancer Patients Using [18F] 4-L-Fluoroglutamine (2S,4R) - Full Text View

Purpose

This is a Phase I study. This study is the first time that a new experimental drug called 18FFluoroglutamine, or F-Glutamine, is being used in people. F-Glutamine is a drug designed to be used with PET scanners that can 'see' where F-Glutamine goes in the body, after its injected. PET scanners are one of the kinds of scanners you normally find in a hospital radiology department. The researchers have found that tumors in animals absorb F-Glutamine. The researchers believe that scans with F-Glutamine might be able to find tumors in patients.

This first in-human study is being done to see how long F-Glutamine lasts in the blood, when it is given to people in tiny amounts by an injection, and to see where F-Glutamine goes in the body. If the results of this trial are good, then the study doctors plan to use F-Glutamine in another trial to see if scans with F-Glutamine are better for finding tumors compared to the standard types of scans that doctors use.

Condition	Intervention	Phase
Solid Malignancy Lymphoma	Drug: [18F] 4-L-Fluoroglutamine (2S,4R)	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	A Phase I Study: PET Imaging of Cancer Patients Using [18F] 4-L-Fluoroglutamine (2S,4R)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma Nuclear Scans

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

pharmacokinetic profiles [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The trial-design follows standard guidelines on collecting pharmacokinetic (PK) data for investigational radioactive drugs.1, 29-36 Animal [18F] 4-L-of [18F] 4-L-Fluoroglutamine (2S,4R). Fluoroglutamine (2S,4R) PK data provided a basis for the trial design. Sampling time-points were chosen (1) by anticipated exponential PK; with (2) allometry-based interspecies extrapolation of time-scales.37 As data is available from the first patients, suitability of the time-points will be re-examined. Blood samples will be centrifuged and the plasma pipetted, weighed and counted to determine the plasma time activity concentration curves (% injected dose/liter), as well as for metabolite analysis of the [18F] 4-L-Fluoroglutamine (2S,4R) compound (by radio-HPLC or other fit-forpurpose methodology).

Secondary Outcome Measures:

metabolism [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Blood samples will be centrifuged and the plasma pipetted, weighed and counted to determine the plasma time activity concentration curves (% injected dose/liter), as well as for metabolite analysis of the [18F] 4-L-Fluoroglutamine (2S,4R) compound (by radio-HPLC or other fit-forpurpose methodology).
bio distribution [ Time Frame: 2 years ] [ Designated as safety issue: No ]
These data will be obtained in the form of serial PET imaging to detect and quantify changes [18F] 4-L-Fluoroglutamine (2S,4R) biodistribution at multiple time-points, as well as serial venous blood-assays. Our PET scans are routinely corrected for attenuation and scatter and adjusted for system sensitivity and provide quantitative images of the tracer concentration within the imaging field of view, which is often reported in terms of standardized uptake values (SUV) (= μCi found/gm tissue / μCi injected/gm body mass).
radiation dosimetry [ Time Frame: 2 years ] [ Designated as safety issue: No ]
OLINDA 1.1 software, an FDA-approved radiation-dosimetry software package42, 43 will be used to obtain absorbed dose & effective dose measurements. In brief, this entails its automated application of the MIRD formalism to the experimental time-integrated activity coefficients, with dose-factor values defined by standard isotope data and a hermaphroditic anthropomorphic model.34, 36, 38, 44 . OLINDA implements conventional biokinetic models of the urinary bladder and gastrointestinal tract to account for the dosimetric contribution of radioactive excreta.

Estimated Enrollment:	30
Study Start Date:	September 2012
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: [18F] 4-L-Fluoroglutamine (2S,4R) This pilot, first in-human microdose PET trial of the positron-emitting agent [18F] 4-L-Fluoroglutamine (2S,4R) will be an open-label study. The [18F] 4-L-Fluoroglutamine (2S,4R) agent will be administered by bolus intravenous injection. In all study patients, the pharmacokinetics, metabolism, and biodistribution of [18F] 4-L-Fluoroglutamine (2S,4R) will be evaluated by non-invasive blood- and PET-based assays, at multiple time points (see Table 1,) during one day. At the discretion of the investigator, scan 3 can be waived.	Drug: [18F] 4-L-Fluoroglutamine (2S,4R) Thirty cancer patients will receive an injection of a 0.5 to 15 mCi of [18F] 4-LFluoroglutamine (2S,4R) , followed by serial PET/CT scanning and blood draws, (at the disrection of the investigator) over a period of 3.5 hours, on a single day. At the discretion of the investigator, scan 3 can be waived. Immediately prior to injection of the radiotracer, a blood sample will be obtained for measurement of serum glutamine level. The serum glutamine level will be assayed, if necessary, as part of an amino acid screen assay.

Arms

Assigned Interventions

Experimental: [18F] 4-L-Fluoroglutamine (2S,4R)

This pilot, first in-human microdose PET trial of the positron-emitting agent [18F] 4-L-Fluoroglutamine (2S,4R) will be an open-label study. The [18F] 4-L-Fluoroglutamine (2S,4R) agent will be administered by bolus intravenous injection. In all study patients, the pharmacokinetics, metabolism, and biodistribution of [18F] 4-L-Fluoroglutamine (2S,4R) will be evaluated by non-invasive blood- and PET-based assays, at multiple time points (see Table 1,) during one day. At the discretion of the investigator, scan 3 can be waived.

Drug: [18F] 4-L-Fluoroglutamine (2S,4R)

Thirty cancer patients will receive an injection of a 0.5 to 15 mCi of [18F] 4-LFluoroglutamine (2S,4R) , followed by serial PET/CT scanning and blood draws, (at the disrection of the investigator) over a period of 3.5 hours, on a single day. At the discretion of the investigator, scan 3 can be waived. Immediately prior to injection of the radiotracer, a blood sample will be obtained for measurement of serum glutamine level. The serum glutamine level will be assayed, if necessary, as part of an amino acid screen assay.

Eligibility

Ages Eligible for Study:	21 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with history of histologically-confirmed solid malignancy and/or lymphoma (histology confirmed by MSKCC Department of Pathology.) Disease measurable or evaluable as defined by RECIST 1.1 or other tumor response criteria from an MSKCC IRB-approved clinical research protocol. NOTE: Study patients do not need to be participating in an MSKCC approved clinical trial prior to study recruitment.
Age between 21-90
Negative serum pregnancy test for female patients of childbearing age and potential (as defined by MSKCC Standards & Guidelines), from assays obtained <2 weeks prior to study enrollment. Patients will be advised against having unprotected sexual intercourse from the time of the negative serum pregnancy test until after completing their participation in the study.

Exclusion Criteria:

Inability or refusal to have at least one peripheral intravenous line for intravenous access (as applicable to the day of [18F] 4-L-Fluoroglutamine (2S,4R) injection and blood draws.)
Breast-feeding
Refusal or inability to tolerate the scanning procedure (e.g., due to claustrophobia)
Hepatic: from assays obtained <2 weeks prior to study enrollment For each patient, the upper limit of normal (ULN) value for a particular assay will be defined by the normal reference values of the laboratory that performed the assay.
Bilirubin > 1.5 x (ULN)
AST/ALT >2.5 x ULN
Albumin < 3 g/dl
GGT > 2.5 x ULN IF Alkaline phosphatase > 2.5 x ULN.
Renal: Creatinine >1.5 x ULN or creatinine clearance < 60 mL/min, from assays obtained <2 weeks prior to study enrollment
Acute major illness (e.g., unstable cardiovascular condition, etc.)
Patients with diabetes mellitus that are taking diabetes medication at the time of the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01697930

Contacts

Contact: Mark Dunphy, D.O.	212-639-8131
Contact: David Kelsen, MD	646-888-4179

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Mark Dunphy, DO 212-639-8131
Contact: David Kelsen, MD 646-888-4179
Principal Investigator: Mark Dunphy, DO

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Mark Dunphy, D.O.

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01697930 History of Changes
Other Study ID Numbers:	12-168
Study First Received:	September 26, 2012
Last Updated:	April 8, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

PET Imaging
18F] 4-L-Fluoroglutam (2S,4R)
12-168

Additional relevant MeSH terms:

Neoplasms
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 22, 2013