Clinical trial NCT04807582: Measuring Fatty Acid Oxidation in Cerebral Metastases Using [18F]FPIA
Official title: Determining the Magnitude of Early Steps of Fatty Acid Oxidation in Cerebral Metastases Using [18F]FPIA PET/MRI
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cerebral Metastases
Keywords: PET/MRI
Fatty Acid Oxidation
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2021-03-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with radiological evidence of cerebral metastases on MRI that are either treatment naïve or have been treated with SRS +/- combination therapy within 4-8 weeks.

Brief summary: Cerebral metastases represent a significant problem for oncological management. It is estimated that 20-40% of patients with cancer will develop metastatic cancer to the brain during the course of their illness. 18F-fluoropivalate (\[18F\]FPIA) is a new tracer that images short chain fatty acid (SCFA) uptake in tumours, a key component of fatty acid oxidation.

The aim of this study is to quantify the degree of early step fatty acid oxidation in cerebral metastases as imaged by \[18F\]FPIA Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI).

The investigators hypothesise that FPIA uptake will be higher in metastases that are treatment naïve compared to those that have undergone treatment, in keeping with viable tumour cells having a high propensity to generate ATP and NADPH via fatty acid oxidation under bioenergetic stress.

Detailed description: 24 evaluable patients with radiological evidence of cerebral metastases on MRI will be enrolled into the study (12 who are treatment naïve + 12 who have completed Stereotactic Radiosurgery (SRS)+/- combination therapy). The patients invited to participate in the study will provide written informed consent. \[18F\]FPIA PET/MRI imaging will only be performed once patients have satisfied the inclusion and exclusion criteria. Once these have been satisfied, eligible patients will proceed to \[18F\]FPIA PET/MRI.

On the day of imaging the patients will undergo a blood test to measure plasma concentrations of carnitine (approximately 6mls). During the scan, a single dose of \[18F\]FPIA (maximum, 370 MBq) IV will be administered to the participant followed by a whole brain dynamic PET/MRI scan over 66 minutes. During the MRI sequences, the patient will receive a 2 stage IV bolus of Gadolinium contrast medium administered through a peripheral venous cannula.

Eligibility criteria: Inclusion Criteria:

A) Treatment naïve

or

B) SRS+/- combination treated - Patients that have completed the SRS part of a combination regime enabling a 4-8 week post-SRS treatment PET/MRI scan.

and

C) That fulfil the following criteria:

1. Age ≥18.
2. Target metastases size ≥ 1cm.
3. WHO performance status 0 - 2.
4. If female, the subject is either post-menopausal (at least 1 year), or surgically sterilized (has had a documented bilateral oophorectomy and/or documented hysterectomy for at least 2 years), or if of childbearing potential, must have a negative urine beta human chorionic gonadotropin (beta-hCG) pregnancy test done prior to tracer administration.
5. The subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
6. The subject has a satisfactory medical history as judged by the investigator with no significant co-morbidities.
7. The subject's clinical and laboratory tests are within normal limits and/or considered clinically insignificant.

Exclusion Criteria:

1. The subject is pregnant or lactating.
2. Any other chronic illness that will or musculoskeletal condition that would not allow comfortable performance of a PET study.
3. Prior use within 14 days of enrolment or concurrent therapy with any other investigational agent.
4. Unsatisfactory renal function (eGFR\<30).
5. The subject has non-MRI compatible devices (e.g.a pacemaker, an implantable cardioverter-defibrillator (ICD), a nerve stimulator, a cochlear implant or a drug pump) or implanted material (e.g. non-MRI compatible sternal wires, biostimulators, metals or alloys).

Primary outcomes:
measure: Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Treatment naïve Patients.
timeFrame: On the scan day up to 60 minutes
measure: Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Patients Treated With Stereotactic Radiosurgery (SRS).
timeFrame: On the scan day (4-8 weeks post-SRS treatment)
Secondary outcomes:
measure: Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve.
timeFrame: On the scan day (4-8 weeks post-SRS treatment)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
References: