TRLS-02. Trial in Progress: A Multicenter Phase 3 Study to Establish the Diagnostic Performance of (18)F-Fluciclovine PET in Detecting Recurrent Brain Metastases after Radiation Therapy (REVELATE)

BACKGROUND: Brain metastases occur in up to 40% of patients with cancer and are associated with poor prognosis and considerable levels of recurrence. Consequently, close follow-up with serial brain MRI is performed post-treatment to monitor for recurrent disease. Although conventional MRI (CE-T1-weighted and FLAIR/T2-weighted) is the recommended follow-up modality, it has poor specificity with limited ability to differentiate between true disease recurrence and treatment-related changes such as radiation necrosis. Therefore, alternative imaging options are sought in order to help physicians confidently diagnose treatment-related changes and thus reliably stratify the risk of continuation of a therapeutic regimen, especially given the morbidity associated with current treatments. Amino acid PET imaging agent, 18F-fluciclovine, has increased uptake in brain tumors relative to normal tissue and may be useful for detecting recurrent brain metastases. METHODS: NCT04410133 is a prospective, open-label, single-arm, single-dose (185 MBq ±20%) study with a primary objective to confirm the diagnostic performance of (18)F-fluciclovine PET (read with conventional MRI for anatomical reference) for detection of recurrent brain metastases where MRI is equivocal. Approximately 150 subjects with solid tumor brain metastases who have undergone radiation therapy will be enrolled in this multicenter trial (~18 US sites) if they have a lesion considered equivocal on MRI that requires further confirmatory diagnostic procedures such as biopsy/neurosurgical intervention or clinical follow-up. Subjects will undergo 18F-fluciclovine PET <28 days after the equivocal MRI and 2–21 days pre-biopsy/neurosurgical intervention. Clinical follow-up will occur for 6m post-18F-fluciclovine PET. Secondary objectives include evaluation of subject- and lesion-level 18F-fluciclovine negative and positive percent agreement (equivalent to specificity and sensitivity respectively) for recurrent brain metastases, inter-reader and intra-reader agreement, and safety evaluations. Enrolment began in October 2020 and the trial is open at the time of submission.