LOCATE: 18F Fluciclovine (FACBC) PET/CT in Patients With Rising PSA After Initial Prostate Cancer Treatment

• Sponsor: Blue Earth Diagnostics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02680041
• Collaborator: American College of Radiology (Other), IND 2 Results LLC (Industry), Syne Qua Non Limited (Industry)
• Enrollment: 221
• Locations: 17
• Arm: 1
• Actual Duration (Months): 17
• Patients Per Site: 13
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This prospective study will enroll up to 330 men with PSA-persistent or PSA-recurrent prostate cancer after curative-intent primary therapy and negative or equivocal findings on standard-of-care imaging. Consenting participants will be imaged with 18F-fluciclovine PET/CT. Site clinicians will manage study subjects per standard practices and will document any change in treatment based on review of 18F-fluciclovine PET/CT findings. All participants will be followed for up to 6 months, with clinical data collected for this study. An interdisciplinary panel will provide expert guidance to local readers on request. The final reporting of the PET/CT scan will be a single report by the local reader following any such discussion.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: The Impact of 18F Fluciclovine (FACBC) PET/CT (Positron Emission Computed Tomography) on Management of Patients With Rising PSA (Prostate-specific Antigen) After Initial Prostate Cancer Treatment
• Actual Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 18F-fluciclovine PET CT Single intravenous administration of 18F-fluciclovine PET CT.	Drug: 18F-fluciclovine PET CT; Subjects will undergo a fluciclovine F18 PET/CT scan in addition to standard of care monitoring. The results of this scan may influence further treatment; Other Names: FACBC

Outcome Measures

Primary Outcome Measures

1. The Fraction of Patients for Whom 18F-fluciclovine PET/CT Alters Patient Planned Treatment Through Detection of Disease. [2-22 days post PET CT]

   The change of management will be based on referring physician questionnaires completed pre- and post- 18F-fluciclovine PET/CT

Secondary Outcome Measures

1. The Fraction of Patients for Whom 18F-fluciclovine PET/CT Alters Patient Actual Treatment [6 months]

   The change of management will be based on referring physician questionnaires completed pre- 18F-fluciclovine PET/CT and changes reported at 6 month follow-up. Investigators were instructed to assess any clinically significant change from the revised management plan.

2. The Rate of Detection of Any Disease Site by 18F-fluciclovine PET/CT in the Study Population [1 week]

   The percentage of subjects who have disease detectable by 18F-fluciclovine PET/CT

3. The Rate of Detection of Disease in 1) Prostate and Prostate Bed and 2) Extra-prostatic Regions With 18F-fluciclovine PET/CT in the Study Population [1 week]

   The percentage of subjects who have disease detectable by 18F-fluciclovine PET/CT 1) in the pelvis and 2) distally

4. The Positive Predictive Value (PPV) of 18F-fluciclovine PET/CT for Regional Disease Compared to Biopsy in Those Patients Who Undergo Biopsy or in Case of Bony Disease a Correlation With MRI or Biopsy [6 months]

   Based on the ratio of positive findings in the pelvis on 18F-fluciclovine PET/CT which are confirmed by histological examination of tissue or MRI

5. The PPV of 18F-fluciclovine PET/CT for Distant Disease Compared to Biopsy in Those Patients Who Undergo a Biopsy or in Case of Bony Disease a Correlation With MRI or Biopsy [6 months]

   Based on the ratio of positive findings outside the pelvis on 18F-fluciclovine PET/CT which are confirmed by histological examination of tissue or MRI

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• History of histologically confirmed adenocarcinoma of the prostate post curative-intent local treatment (radical prostatectomy, local radiotherapy, brachytherapy).

• Suspicion of recurrent prostate carcinoma after previous presumed definitive therapy for organ confined disease defined as :

• Post prostatectomy: Detectable or rising PSA level that is >0.2 ng/mL with a second confirmatory level of >0.2 ng/mL

• Post non-prostatectomy: PSA rise ≥ 2ng/mL over nadir

• Negative or equivocal findings on standard-of-care imaging for restaging of disease in the previous 60 days consisting of: Whole-body 99mTc bone scintigraphy or NaF PET-CT; and either CT or MRI of the pelvis (or the abdomen and pelvis).

• Being considered for salvage therapy

• Any non-surgical local treatment such as previous cryotherapy, external beam radiation, or HiFU (Ultrasound) must have occurred at least 1 year in the past.

• Previous brachytherapy treatment will have occurred at least 2 years in the past

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Ongoing treatment with any systemic therapy intended for the treatment of prostate cancer (e.g., antiandrogen or LHRH agonist or antagonist)

• Androgen deprivation therapy (ADT) in the past 3 months

• History of bilateral orchidectomy

• Inability to tolerate 18F-fluciclovine PET/CT

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	Tower Urology	Los Angeles	California	United States	90048
4	Genesis Research, LLC	San Diego	California	United States	92123
5	University of Florida	Jacksonville	Florida	United States	32209
6	Loyola University Medical Center	Maywood	Illinois	United States	60153
7	Roudebush VA Medical Center	Indianapolis	Indiana	United States	46202
8	University of Louisville	Louisville	Kentucky	United States	40202
9	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
10	Coastal Urology Associates	Brick	New Jersey	United States	08724
11	Manhattan Medical Research	New York	New York	United States	10016
12	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
13	Urologic Consultants of SE Pennsylvania	Bala-Cynwyd	Pennsylvania	United States	19004
14	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
16	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
17	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Blue Earth Diagnostics
• American College of Radiology
• IND 2 Results LLC
• Syne Qua Non Limited

Investigators

• Study Chair: Umar Mahmood, MD, PhD, Harvard Medical School (HMS and HSDM)
• Study Director: Peter Gardiner, MB ChB, MRCP, FFPM, Blue Earth Diagnostics

Study Documents (Full-Text)

• Study Protocol - Jun 7, 2017
• Statistical Analysis Plan - Mar 5, 2018

More Information

Publications

None provided.

• Responsible Party: Blue Earth Diagnostics
• ClinicalTrials.gov Identifier: NCT02680041
• Other Study ID Numbers: BED003
• First Posted: Feb 11, 2016
• Last Update Posted: Jan 28, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	The study was conducted between 01 June 2016 (first patient, screening visit) and 01 November 2017 (last patient, last contact) at 17 sites in the USA. Overall 17 sites were initiated, of which 15 sites enrolled patients.

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT.
Period Title: Overall Study
STARTED	221
Received 18F-fluciclovine	213
COMPLETED	211
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET/CT.
Overall Participants	213
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67.0
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	213 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 4.2%
Not Hispanic or Latino	202 94.8%
Unknown or Not Reported	2 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%
Asian	3 1.4%
Native Hawaiian or Other Pacific Islander	2 0.9%
Black or African American	17 8%
White	188 88.3%
More than one race	0 0%
Unknown or Not Reported	2 0.9%
Region of Enrollment (participants) [Number]
United States	213 100%

Outcome Measures

1. Primary Outcome

Title	The Fraction of Patients for Whom 18F-fluciclovine PET/CT Alters Patient Planned Treatment Through Detection of Disease.
Description	The change of management will be based on referring physician questionnaires completed pre- and post- 18F-fluciclovine PET/CT
Time Frame	2-22 days post PET CT

Outcome Measure Data

Analysis Population Description

For the primary analysis population, of the 213 patients included in the EAS, 122 patients with a positive 18F-fluciclovine scan and 91 patients with a negative 18F-fluciclovine scan had a pre 18F-fluciclovine PET/CT treatment management plan.

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT. 18F-fluciclovine PET CT: Subjects will undergo a fluciclovine F18 PET/CT scan in addition to standard of care monitoring. The results of this scan may influence further treatment
Measure Participants	213
Patients with Revised Management Plan	126 59.2%
No Revision to Management Plan	87 40.8%
Patients with Revised Management Plan	88 41.3%
No Revision to Management Plan	34 16%
Patients with Revised Management Plan	38 17.8%
No Revision to Management Plan	53 24.9%

2. Secondary Outcome

Title	The Fraction of Patients for Whom 18F-fluciclovine PET/CT Alters Patient Actual Treatment
Description	The change of management will be based on referring physician questionnaires completed pre- 18F-fluciclovine PET/CT and changes reported at 6 month follow-up. Investigators were instructed to assess any clinically significant change from the revised management plan.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

211 participants completed the study (actual treatment assessed at study completion). Results also presented by 18F-fluciclovine PET CT results.

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT.
Measure Participants	211
Change from the revised management plan	80 37.6%
No change from the revised management plan	131 61.5%
Change from the revised management plan	47 22.1%
No change from the revised management plan	74 34.7%
Change from the revised management plan	33 15.5%
No change from the revised management plan	57 26.8%

3. Secondary Outcome

Title	The Rate of Detection of Any Disease Site by 18F-fluciclovine PET/CT in the Study Population
Description	The percentage of subjects who have disease detectable by 18F-fluciclovine PET/CT
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

Results presented for Full Analysis Set

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT.
Measure Participants	213
Count of Participants [Participants]	122 57.3%

4. Secondary Outcome

Title	The Rate of Detection of Disease in 1) Prostate and Prostate Bed and 2) Extra-prostatic Regions With 18F-fluciclovine PET/CT in the Study Population
Description	The percentage of subjects who have disease detectable by 18F-fluciclovine PET/CT 1) in the pelvis and 2) distally
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

Participants may have lesions detected in both regions (prostate/prostate bed and extra-prostatic).

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT.
Measure Participants	213
Prostate or Prostate Bed	64 30%
Extra-prostatic	80 37.6%

5. Secondary Outcome

Title	The Positive Predictive Value (PPV) of 18F-fluciclovine PET/CT for Regional Disease Compared to Biopsy in Those Patients Who Undergo Biopsy or in Case of Bony Disease a Correlation With MRI or Biopsy
Description	Based on the ratio of positive findings in the pelvis on 18F-fluciclovine PET/CT which are confirmed by histological examination of tissue or MRI
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Only scans graded as positive or negative by the adjudication panel were included in these calculations.

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT.
Measure Participants	45
Number (95% Confidence Interval) [Percentage of scans]	100

6. Secondary Outcome

Title	The PPV of 18F-fluciclovine PET/CT for Distant Disease Compared to Biopsy in Those Patients Who Undergo a Biopsy or in Case of Bony Disease a Correlation With MRI or Biopsy
Description	Based on the ratio of positive findings outside the pelvis on 18F-fluciclovine PET/CT which are confirmed by histological examination of tissue or MRI
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Only scans graded as positive or negative by the adjudication panel were included in these calculations.

Arm/Group Title	18F-fluciclovine PET CT
Arm/Group Description	Single intravenous administration of 18F-fluciclovine PET CT.
Measure Participants	37
Number (95% Confidence Interval) [Percentage of scans]	100

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 PET CT.
All Cause Mortality
	18F-fluciclovine PET CT
	Affected / at Risk (%)	# Events
Total	0/213 (0%)
Serious Adverse Events
	18F-fluciclovine PET CT
	Affected / at Risk (%)	# Events
Total	0/213 (0%)
Other (Not Including Serious) Adverse Events
	18F-fluciclovine PET CT
	Affected / at Risk (%)	# Events
Total	44/213 (20.7%)
Cardiac disorders
Atrial fibrilation	1/213 (0.5%)
Gastrointestinal disorders
Diarrhoea	6/213 (2.8%)
Constipation	2/213 (0.9%)
Abdominal discomfort	1/213 (0.5%)
Abdominal pain	1/213 (0.5%)
Dyspepsia	1/213 (0.5%)
Inguinal hernia	1/213 (0.5%)
Nausea	1/213 (0.5%)
General disorders
Oedema peripheral	2/213 (0.9%)
Excercise tolerance decreased	1/213 (0.5%)
Fatigue	1/213 (0.5%)
Feeling cold	1/213 (0.5%)
Injection site extravasation	1/213 (0.5%)
Injection site pain	1/213 (0.5%)
Pyrexia	1/213 (0.5%)
Infections and infestations
Urinary Tract Infection	2/213 (0.9%)
Rectal abscess	1/213 (0.5%)
Investigations
Blood creatine phosphokinase increased	1/213 (0.5%)
Blood creatine increased	1/213 (0.5%)
Blood potassium increased	1/213 (0.5%)
Blood urea increased	1/213 (0.5%)
Carbon dioxide decreased	1/213 (0.5%)
Waist circumference increased	1/213 (0.5%)
Metabolism and nutrition disorders
Hyperchloreamia	1/213 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/213 (0.5%)
Flank pain	1/213 (0.5%)
Intervertrabral disc degeneration	1/213 (0.5%)
Muscle spasms	1/213 (0.5%)
Muscular weakness	1/213 (0.5%)
Musculoskeletal stiffness	1/213 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	2/213 (0.9%)
Adenocarcinoma of colon	1/213 (0.5%)
Oesophageal carcinoma	1/213 (0.5%)
Nervous system disorders
Headache	6/213 (2.8%)
Dysgeusia	1/213 (0.5%)
Hydrocephalus	1/213 (0.5%)
Lethargy	1/213 (0.5%)
Parkinson's disease	1/213 (0.5%)
Psychiatric disorders
Anxiety	2/213 (0.9%)
Emotional disorder	1/213 (0.5%)
Insomnia	1/213 (0.5%)
Listless	1/213 (0.5%)
Renal and urinary disorders
Haematuria	2/213 (0.9%)
Nocturia	2/213 (0.9%)
Pollakiuria	2/213 (0.9%)
Urinary Incontinence	2/213 (0.9%)
Dysuria	1/213 (0.5%)
Hypertonic bladder	1/213 (0.5%)
Micturition urgency	1/213 (0.5%)
Stress urinary incontinence	1/213 (0.5%)
Urinary retention	1/213 (0.5%)
Reproductive system and breast disorders
Breast tenderness	1/213 (0.5%)
Gynaecomastia	1/213 (0.5%)
Nipple pain	1/213 (0.5%)
Scrotal irritation	1/213 (0.5%)
Skin and subcutaneous tissue disorders
Skin lesion	1/213 (0.5%)
Vascular disorders
Hot flush	2/213 (0.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Neither Institution nor Investigator will submit for publication or public disclosure any publication or disclosure based on the results of the Study until after the first to occur of (a) publication of the Multi-Center Clinical Trial results; (b) notification by Sponsor that the Multi-Center Clinical Trial submission is no longer planned; or (c) the eighteen (18) month anniversary of the completion or early termination of the Multi-Center Clinical Trial.