A Prospective, Bicentric Evaluation of Fluciclovine PET-imaging in Patients with Prior Negative or Inconclusive PSMA-ligand PET (REFINE)

Prospective Evaluation of Fluciclovine (18F) PET/CT in Patients with Prior Negative PSMA PET/CT

The REFINE study is evaluating whether a fluciclovine (18F) PET/CT scan can detect recurrent prostate cancer in patients whose previous PSMA PET/CT was negative or inconclusive.

Study Overview

• Status: Recruiting
• Conditions: Biochemical Recurrence of Malignant Neoplasm of Prostate

Detailed Description

The REFINE study is a prospective, bicentric observational trial conducted at two specialized nuclear medicine centers in Germany to evaluate the technical performance of fluciclovine (18F) PET/CT imaging in a real-world clinical setting. Patients with prostate cancer recurrence after definitive treatment who previously underwent a negative or inconclusive PSMA PET/CT are enrolled and observed for 12 months. Each participant undergoes a fluciclovine PET/CT scan as part of their normal clinical routine, with all images pseudonymized and stored in a central database where three independent nuclear medicine physicians, blinded to the local site's interpretation, review each scan. In addition to the initial imaging, follow-up assessments are conducted at one month and 12 months to validate scan findings; a questionnaire sent to the referring physician at one month helps capture any changes in the intended treatment plan, while comprehensive follow-up data-including additional imaging studies, PSA levels, treatment outcomes, and histopathological findings when available-are collected at 12 months. This follow-up information serves as a composite reference standard to distinguish true positive lesions from false positives, with criteria based on changes in lesion size, response to treatment, and confirmatory imaging or biopsy results, as well as to identify any false negatives.

• Study Type: Observational
• Enrollment (Estimated): 94

Contacts and Locations

• Study Contact: Name: Matthias Eiber, MD; Phone Number: +49 89 4140 0; Email: matthias.eiber@tum.de

Study Locations

• Germany
  • Bavaria
    • Augsburg, Bavaria, Germany, 86156
      • Not yet recruiting
      • University Hospital Augsburg
      • Contact: Constantin Lapa, MD; Phone Number: +49 821 4003040; Email: info@uk-augsburg.de
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • TUM University Hospital
      • Contact: Matthias Eiber, MD; Phone Number: +49 89 4140 0; Email: sekretariat@mri.tum.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with a diagnosis of BCR and negative or inconclusive PSMA-ligand PET of previous radically treated PCa, aged ≥18 years old, eligible for fluciclovine PET/CT.

Description

Inclusion Criteria:

• Patient is male and aged >18 years old.
• Patient with a history of localized adenocarcinoma of the prostate with prior curative intent treatment, experiencing BCR of hormone sensitive PCa, following prior treatment with one or more of the following: a) RP, b) RP plus adjuvant therapy, c) RT and/or androgen deprivation therapy [ADT].
• An elevated PSA, clinically suspicious for biochemically recurrent disease, that meets one of the following conditions: 1) Following RP with or without adjuvant therapy: PSA ≥0.2 ng/mL followed by a subsequent confirmatory PSA value ≥0.2 ng/mL and within the total range of 0.2 and 2 ng/ml. PSA must be measured at least 6 weeks after RP. 2) Following RT (e.g. radical radiotherapy or brachytherapy) as the primary treatment: nadir +2 ng/mL and within the total range of 2 and 4 ng/ml

Exclusion Criteria:

• Patients with any medical condition or circumstance (including receiving an investigational product) that the investigator believes may compromise the data collected or lead to a failure to fulfill the study requirements.
• Current or recent androgen deprivation therapy (ADT) within 3 months prior to the start of the study, which includes surgical orchidectomy, continuous or intermittent LHRH agonist/antagonist, and first-/second-generation anti androgen alone or combined with LHRH agonist/antagonist.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Prostate cancer patients with biochemical recurrence after negative/inconclusive PSMA PET/CT; This cohort comprises male patients with biochemically recurrent prostate cancer following definitive treatment-such as surgery or radiotherapy-who have previously undergone a PSMA PET/CT scan that was either negative or inconclusive. The primary intervention of interest is the fluciclovine (18F) PET/CT scan, which is performed as part of their routine clinical care to detect sites of recurrent disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-level detection rate	The patient-level detection rate of fluciclovine (18F) PET/CT in patients with a prior negative or inconclusive PSMA-ligand PET/CT	From enrollment to the end of observation at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Region level detection rate	Region level detection rate of fluciclovine (18F) PET/CT with prior negative or inconclusive PSMA-ligand PET/CT	From enrollment to the end of observation at 1 year
Detection rate stratified by PSA level	Detection rate (patient and region level) of fluciclovine (18F) PET/CT with prior negative or inconclusive PSMA-ligand PET/CT, stratified by PSA level	From enrollment to the end of observation at 1 year
Intended management change	The proportion of patients with a change of intended management after fluciclovine (18F) PET/CT	From enrollment to the end of observation at 1 year
Interreader agreement	Reader kappa statistics of fluciclovine (18F) scan interpretation by the blinded independent readers	From enrollment to the end of observation at 1 year

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Matthias Eiber, MD, Technical University of Munich

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: PET; prostate cancer; PSMA; prostate; BCR; biochemical recurrence; fluciclovine
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Disease Attributes; Neoplasms; Prostatic Neoplasms; Recurrence
• Other Study ID Numbers: 2024-643-S-NP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Sharing of anonymous data might be possible upon reasonable scientific request.

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No