Cancer of the Prostate
Conditions
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
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.
Interventions
Radioligand for PET CT scanning
Sponsors
Innovate UK
Syne Qua Non Limited
IND 2 Results LLC
Blue Earth Diagnostics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
PET Imaging study
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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). i. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Response Rate to Radical Salvage Therapy | 7 months | To establish the proportion of patients who have a sustained response to radical salvage therapy. |
| 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 |
| 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. |
Countries
United Kingdom
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.
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Single intravenous administration of 18F-Fluciclovine for PET Scan
18F-Fluciclovine PET CT: Radioligand for PET CT scanning | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Screening failure | 5 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Continuous | 67.0 years |
| Body Mass Index | 26.50 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 176.0 cm |
| Region of Enrollment United Kingdom | 104 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 104 Participants |
| Weight | 82.80 Kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 104 |
| other Total, other adverse events | 31 / 104 |
| serious Total, serious adverse events | 1 / 104 |
Outcome results
Primary
Impact on Patient Treatment /Management
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
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 18F-Fluciclovine PET CT | Impact on Patient Treatment /Management | Overall Evaluable Analysis Set | Patients with Revised Management Plan | 66 Participants |
| 18F-Fluciclovine PET CT | Impact on Patient Treatment /Management | Overall Evaluable Analysis Set | No Revision to Management Plan | 38 Participants |
| 18F-Fluciclovine PET CT | Impact on Patient Treatment /Management | Positive 18F-fluciclovine Scan | Patients with Revised Management Plan | 53 Participants |
| 18F-Fluciclovine PET CT | Impact on Patient Treatment /Management | Positive 18F-fluciclovine Scan | No Revision to Management Plan | 5 Participants |
| 18F-Fluciclovine PET CT | Impact on Patient Treatment /Management | Negative 18F-fluciclovine Scan | Patients with Revised Management Plan | 13 Participants |
| 18F-Fluciclovine PET CT | Impact on Patient Treatment /Management | Negative 18F-fluciclovine Scan | No Revision to Management Plan | 33 Participants |
Secondary
PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR
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
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup 0 to 0.2 (ng/mL) | 33.3 percentage of Detection Rate |
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup >0.2 to 0.5 (ng/mL) | 25.9 percentage of Detection Rate |
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup >0.5 to 1.0 (ng/mL) | 36.4 percentage of Detection Rate |
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup >1.0 to 2.0 (ng/mL) | 20 percentage of Detection Rate |
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup >2.0 to 5.0 (ng/mL) | 91.7 percentage of Detection Rate |
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup >5.0 to 10.0 (ng/mL) | 90.9 percentage of Detection Rate |
| 18F-Fluciclovine PET CT | PSA Threshold for Positive Lesion Detection by 18F Fluciclovine PET/CT in BCR | PSA Subgroup >10 (ng/mL) | 100 percentage of Detection Rate |
Secondary
Response Rate to Radical Salvage Therapy
To establish the proportion of patients who have a sustained response to radical salvage therapy.
Time frame: 7 months
Population: Full Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy all | Stable disease | 5 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy all | Treatment response | 43 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy all | Disease progression | 8 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy guided by 18F-fluciclovine | Treatment response | 15 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy guided by 18F-fluciclovine | Stable disease | 0 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy guided by 18F-fluciclovine | Disease progression | 2 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy not guided by 18F-fluciclovine | Treatment response | 28 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy not guided by 18F-fluciclovine | Stable disease | 5 Participants |
| 18F-Fluciclovine PET CT | Response Rate to Radical Salvage Therapy | Salvage therapy not guided by 18F-fluciclovine | Disease progression | 6 Participants |
Secondary
Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT.
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
Population: Treatment-emergent Adverse Events
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 18F-Fluciclovine PET CT | Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT. | TEAEs Unrelated | 18 Participants |
| 18F-Fluciclovine PET CT | Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT. | TEAEs Possibly | 8 Participants |
| 18F-Fluciclovine PET CT | Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT. | TEAEs Probably | 0 Participants |
| 18F-Fluciclovine PET CT | Safety of 18F Fluciclovine Injection in Patients Undergoing PET/CT. | TEAEs Definitely | 1 Participants |