FALCON: Fluciclovine (18F) PET/CT in biochemicAL reCurrence Of Prostate caNcer

• Sponsor: Blue Earth Diagnostics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02578940
• Collaborator: Innovate UK (Other), Syne Qua Non Limited (Industry), IND 2 Results LLC (Industry)
• Enrollment: 104
• Locations: 7
• Arm: 1
• Actual Duration (Months): 31.7
• Patients Per Site: 14.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The main aim is to assess the impact of using 18F-fluciclovine (as a PET imaging radiotracer) on the clinical and treatment decision required for managing patients with biochemically recurrent prostate cancer (BCR) who are being considered for salvage treatment with the intention of providing disease cure. Also, this study will consolidate the information regarding diagnostic performance of fluciclovine PET/CT in a large number of prospectively followed patients at several centres in the UK and assess the effect of PSA level on the likelihood of detecting cancer lesions by 18F-fluciclovine

Condition or Disease	Intervention/Treatment	Phase
Cancer of the Prostate	Drug: 18F-Fluciclovine PET CT	Phase 3

Detailed Description

Proposed Research In the setting of growing single-centre evidence of superior diagnostic performance of 18F-fluciclovine PET/CT in BCR, our primary aim is to assess its clinical impact on treatment decisions in a multi-centre study in patients with BCR being considered for radical salvage treatment (with curative intent). In addition, we aim to further characterise its diagnostic performance, afforded by larger numbers of patients from multi-centre recruitment. We also aim to assess the effect of PSA level on probability of lesion detection by 18F-fluciclovine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: PET Imaging studyPET Imaging study
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase 3, Open-label Study to Assess the Clinical Utility of Fluciclovine (18F) PET/CT in Patients With Prostate Cancer With Biochemical Recurrence After Radical Treatment
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: May 17, 2017
• Actual Study Completion Date: Jun 22, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm Single intravenous administration of 18F-Fluciclovine for PET Scan	Drug: 18F-Fluciclovine PET CT; Radioligand for PET CT scanning; Other Names: FACBC

Outcome Measures

Primary Outcome Measures

1. Impact on Patient Treatment /Management [1 month]

   The record of the revised management plan post fluciclovine (18F) PET/CT scan in comparison to the pre-scan intended management plan.

Secondary Outcome Measures

1. Response Rate to Radical Salvage Therapy [7 months]

   To establish the proportion of patients who have a sustained response to radical salvage therapy.

2. PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR [1 month]

   PSA levels in relation to scan positivity were analysed to determine the optimal PSA threshold for detecting recurrent prostate cancer by 18F fluciclovine PET/CT

3. Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT. [1 month]

   Safety was assessed from data on the occurrence of adverse events (AEs) and changes in clinical laboratory tests, vital signs, injection-site status and physical examination findings from the time of administration of 18F fluciclovine injection throughout the study period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject has had an original diagnosis of PCa and underwent radical curative therapy at least 3 months before enrolment, and has been diagnosed with biochemical recurrence (BCR) on the basis of:

1. Post radical radiotherapy (RRT) / brachytherapy: Increase in PSA level ≥2.0 ng/mL above the nadir level after radiotherapy (RT) or brachytherapy (ASTRO-Phoenix criteria) [53], or

2. Post radical prostatectomy (RP): EITHER two consecutive rises in PSA and final PSA >0.1ng/ml OR three consecutive rises in PSA., This definition is also applicable to subjects with PSA persistence post RP (where the PSA fails to fall to undetectable levels).

1. In addition, the subject post RP, should have a PSA doubling time of ≤15 months OR PSA level ≥1.0 ng/mL at time of recruitment. The PSA doubling time will be calculated using the Memorial Sloan Kettering Cancer Center nomogram (http://www.mskcc.org/nomograms/prostate/psa-doubling-time), based on a minimum of two PSA levels within 12 months of screening, taken after the last recorded nadir PSA available at time of screening.

• The subject has not had previous recurrences of PCa, i.e. this is the first diagnosis of BCR.

• The subject is being considered for radical salvage therapy.

• The subject is able and willing to comply with study procedures, and signed, dated and timed informed consent is obtained before any study-related procedure is performed.

• The subject's Eastern Cooperative Oncology Group [ECOG] performance status 0-2.

• The subject should not have received androgen-deprivation therapy within 3 months of screening.

• The subject has a normal or clinically acceptable medical history and vital signs findings at screening (up to 14 days before administration of study drug).

Exclusion Criteria:

• The subject has been previously included in this study.

• The subject has received, or is scheduled to receive, another investigational medicinal product (IMP) from 1 month before to 1 week after administration of fluciclovine (18F) injection.

• The subject has known hypersensitivity to fluciclovine (18F) injection or any of its constituents.

• The subject has had a choline PET/CT scan within 3 months of the screening visit.

• The subject has bilateral hip prostheses.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Vernon Cancer Centre, Mount Vernon Hospital	Northwood	Middlesex	United Kingdom	HA6 2RN
2	Churchill Hospital	Oxford	Oxfordshire	United Kingdom	OX3 7LE
3	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
4	St James Institute of Oncology	Leeds	Yorkshire	United Kingdom	LS9 7TF
5	Greater Glasgow & Clyde NHS Trust	Glasgow		United Kingdom
6	University College London Hospital	London		United Kingdom	NW1 2BU
7	St Thomas' Hospital	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

• Blue Earth Diagnostics
• Innovate UK
• Syne Qua Non Limited
• IND 2 Results LLC

Investigators

• Principal Investigator: Fergus Gleeson, FRCP FRCR, The Oxford University Hospitals NHS Trust

Study Documents (Full-Text)

• Study Protocol - Jun 4, 2018
• Statistical Analysis Plan - Oct 10, 2018

More Information

Publications

None provided.

• Responsible Party: Blue Earth Diagnostics
• ClinicalTrials.gov Identifier: NCT02578940
• Other Study ID Numbers: BED-004
• First Posted: Oct 19, 2015
• Last Update Posted: Oct 7, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms; Recurrence

Study Results

Participant Flow

Recruitment Details	This study was conducted between 27 November 2015 (first patient, screening visit) and 22 June 2018 (last patient, completed) at seven sites (one did not enrol) in the UK.

Arm/Group Title	Single Arm
Arm/Group Description	Single intravenous administration of 18F-Fluciclovine for PET Scan 18F-Fluciclovine PET CT: Radioligand for PET CT scanning
Period Title: Overall Study
STARTED	109
Received 18F-fluciclovine	104
COMPLETED	103
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	Single intravenous administration of 18F-Fluciclovine for PET Scan 18F-Fluciclovine PET CT: Radioligand for PET CT scanning
Overall Participants	104
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67.0
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	104 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	104 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	104 100%
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]	176.0
Weight (Kg) [Median (Full Range) ]
Median (Full Range) [Kg]	82.80
Body Mass Index (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	26.50

Outcome Measures

1. Primary Outcome

Title	Impact on Patient Treatment /Management
Description	The record of the revised management plan post fluciclovine (18F) PET/CT scan in comparison to the pre-scan intended management plan.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

For the primary analysis population, of the 104 patients included in the EAS, 58 patients with a positive 18F fluciclovine scan and 46 patients with a negative 18F fluciclovine scan had a pre-18F fluciclovine PET/CT management plan.

Arm/Group Title	18F-Fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-Fluciclovine for PET Scan 18F-Fluciclovine PET CT: Radioligand for PET CT scanning
Measure Participants	104
Patients with Revised Management Plan	66 63.5%
No Revision to Management Plan	38 36.5%
Patients with Revised Management Plan	53 51%
No Revision to Management Plan	5 4.8%
Patients with Revised Management Plan	13 12.5%
No Revision to Management Plan	33 31.7%

2. Secondary Outcome

Title	Response Rate to Radical Salvage Therapy
Description	To establish the proportion of patients who have a sustained response to radical salvage therapy.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-Fluciclovine for PET Scan 18F-Fluciclovine PET CT: Radioligand for PET CT scanning
Measure Participants	104
Treatment response	43 41.3%
Stable disease	5 4.8%
Disease progression	8 7.7%
Treatment response	15 14.4%
Stable disease	0 0%
Disease progression	2 1.9%
Treatment response	28 26.9%
Stable disease	5 4.8%
Disease progression	6 5.8%

3. Secondary Outcome

Title	PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR
Description	PSA levels in relation to scan positivity were analysed to determine the optimal PSA threshold for detecting recurrent prostate cancer by 18F fluciclovine PET/CT
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	18F-Fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-Fluciclovine for PET Scan 18F-Fluciclovine PET CT: Radioligand for PET CT scanning
Measure Participants	104
PSA Subgroup 0 to 0.2 (ng/mL)	33.3
PSA Subgroup >0.2 to 0.5 (ng/mL)	25.9
PSA Subgroup >0.5 to 1.0 (ng/mL)	36.4
PSA Subgroup >1.0 to 2.0 (ng/mL)	20
PSA Subgroup >2.0 to 5.0 (ng/mL)	91.7
PSA Subgroup >5.0 to 10.0 (ng/mL)	90.9
PSA Subgroup >10 (ng/mL)	100

4. Secondary Outcome

Title	Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT.
Description	Safety was assessed from data on the occurrence of adverse events (AEs) and changes in clinical laboratory tests, vital signs, injection-site status and physical examination findings from the time of administration of 18F fluciclovine injection throughout the study period.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Treatment-emergent Adverse Events

Arm/Group Title	Treatment-emergent Adverse Events
Arm/Group Description	Number of Subject from SAS who experienced Treatment-emergent Adverse Events
Measure Participants	27
TEAEs Unrelated	18 17.3%
TEAEs Possibly	8 7.7%
TEAEs Probably	0 0%
TEAEs Definitely	1 1%

Adverse Events

Time Frame	As specified in the Statistical Analysis Plan, results are presented as only those treatment-emergent adverse events which occurred up to 42 days after the 18F fluciclovine administration
Arm/Group Title	18F-Fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-Fluciclovine for PET Scan 18F-Fluciclovine PET CT: Radioligand for PET CT scanning
All Cause Mortality
	18F-Fluciclovine PET CT
	Affected / at Risk (%)	# Events
Total	0/104 (0%)
Serious Adverse Events
	18F-Fluciclovine PET CT
	Affected / at Risk (%)	# Events
Total	1/104 (1%)
Renal and urinary disorders
Urinary tract obstruction	1/104 (1%)
Other (Not Including Serious) Adverse Events
	18F-Fluciclovine PET CT
	Affected / at Risk (%)	# Events
Total	31/104 (29.8%)
Gastrointestinal disorders
DIARRHOEA	1/104 (1%)	1
DYSPEPSIA	1/104 (1%)	1
General disorders
APPLICATION SITE REACTION	3/104 (2.9%)	3
FATIGUE	3/104 (2.9%)	3
APPLICATION SITE ERYTHEMA	1/104 (1%)	1
CATHETER SITE BRUISE	1/104 (1%)	1
INJECTION SITE ERYTHEMA	1/104 (1%)	1
Infections and infestations
ORAL HERPES	1/104 (1%)	1
UPPER RESPIRATORY TRACT INFECTION	1/104 (1%)	1
VIRAL UPPER RESPIRATORY TRACT INFECTION	1/104 (1%)	1
Injury, poisoning and procedural complications
POST PROCEDURAL CONTUSION	1/104 (1%)	1
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED	3/104 (2.9%)	3
BIOPSY PROSTATE	1/104 (1%)	1
BLOOD LACTATE DEHYDROGENASE INCREASED	1/104 (1%)	1
ELECTROCARDIOGRAM ABNORMAL	1/104 (1%)	1
Musculoskeletal and connective tissue disorders
GROIN PAIN	1/104 (1%)	1
MYALGIA	1/104 (1%)	1
NECK PAIN	1/104 (1%)	1
NECK MASS	1/104 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MELANOMA RECURRENT	1/104 (1%)	1
Nervous system disorders
HEADACHE	4/104 (3.8%)	4
DIZZINESS	2/104 (1.9%)	2
DYSGEUSIA	2/104 (1.9%)	2
HYPOAESTHESIA	1/104 (1%)	1
PAROSMIA	1/104 (1%)	1
RESTLESS LEGS SYNDROME	1/104 (1%)	1
TREMOR	1/104 (1%)	1
Renal and urinary disorders
URINARY TRACT OBSTRUCTION	1/104 (1%)	1
Respiratory, thoracic and mediastinal disorders
PULMONARY MASS	1/104 (1%)	1
Skin and subcutaneous tissue disorders
ERYTHEMA	1/104 (1%)	1
Vascular disorders
HYPERTENSION	1/104 (1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.