Clinical trial NCT04838626: Study of Diagnostic Performance of [18F]CTT1057 for PSMA-positive Tumors Detection
Official title: Phase II/III Study for Evaluation of the Diagnostic Performance of [18F]CTT1057 PET Imaging for the Detection of PSMA Positive Tumors Using Histopathology as a Standard of Truth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Prostatic Neoplasms
Prostate Cancer
Keywords: [18F]CTT1057
Positron Emission Tomography/Computerized Tomography
PET/CT
Radioligand
Imaging
Primary Staging
PS
Standard of Truth
SoT
Prostate Cancer
PCa
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-04-09
Enrollment: 195
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will receive \[18F\]CTT1057 for PET/CT scan imaging, and surgery will be performed up to 6 weeks after \[18F\]CTT1057 PET for pathology assessment of the tissue specimens.

Additional pharmacokinetics (PK) assessments will be performed on the date of imaging in a subset of approximately 10 patients at the same site.
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study was to evaluate the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of PSMA positive tumors using histopathology as Standard of Truth (SoT). Tissue specimens from both the primary tumor and pelvic lymph nodes dissected during surgery from patients with newly-diagnosed high-risk prostate cancer (PCa) were used for the histopathology assessments.

Detailed description: This was a multi-center, single-arm, open-label prospective study to evaluate the diagnostic performance of vidoflufolastat (18F) as a positron emission tomography (PET) imaging agent for detection and localization of prostate specific membrane antigen (PSMA) positive tumors, using histopathology as standard of truth (SoT). in newly diagnosed high-risk prostate cancer (PCa) patients.

A total of 195 participants were enrolled to ensure that at least 156 participants were evaluable for the co-primary endpoints. Surgery was performed after vidoflufolastat (18F) positron emission tomography/computerized tomography (PET/CT) scan.

The co-primary endpoints of patient-level sensitivity and region-level specificity were assessed by comparing the central reading results of the vidoflufolastat (18F) PET/CT scan to the local histopathology results in the dissected tissue specimens, i.e. both the primary tumor and the dissected Pelvic Lymph Nodes (PLNs).

Eligibility criteria: Inclusion Criteria:

* Untreated high risk biopsy-proven PCa patients according to D'Amico classification (Stage ≥ T2c or PSA level \>20ng/ml or Gleason score ≥8) (D'Amico et al 1998)
* Scheduled or planned radical prostatectomy and extended pelvic lymph node resection up to 6 weeks after the investigational PET/CT scan followed by histopathology assessment
* ECOG performance status 0-2
* Signed informed consent must be obtained prior to participation in the study
* Participants must be adults ≥ 18 years of age

Exclusion Criteria:

* Inability to complete the needed investigational and standard-of-care imaging examinations due to any reason (severe claustrophobia, inability to lie still for the entire imaging time, etc.)
* Any additional medical condition, serious intercurrent illness, concomitant cancer or other extenuating circumstance that, in the opinion of the Investigator, would indicate a significant risk to safety or impair study participation, including, but not limited to, current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, need of indwelling/condom catheters, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, and COVID-19.
* Known allergy, hypersensitivity, or intolerance to \[18F\]CTT1057
* Prior and current use of PSMA targeted therapies
* Prior and current treatment with any ADT (first or second generation), including LHRH analogues (agonists or antagonists)
* Any 5-alpha reductase inhibitors within 30 days before screening
* Patients with small cell or neuroendocrine PCa in more than 50% of biopsy tissue
* Patients with incidental PCa after transurethral resection
* Use of other investigational drugs within 30 days before screening

Primary outcomes:
measure: Patient-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity
timeFrame: vidoflufolastat (18F)7 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Region-level Specificity of Vidoflufolastat (18F) - % Specificity
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
Secondary outcomes:
measure: Patient-level Specificity of Vidoflufolastat (18F) - % Specificity
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Patient-level Positive Predictive Value of Vidoflufolastat (18F)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Patient-level Negative Predictive Value of Vidoflufolastat (18F)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Patient-level Accuracy of Vidoflufolastat (18F)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Region-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Region-level Positive Predictive Value of Vidoflufolastat (18F)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Region-level Negative Predictive Value of Vidoflufolastat (18F)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Region-level Accuracy of Vidoflufolastat (18F)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Region-level Sensitivity of Vidoflufolastat (18F) Scan With Standard of Truth Excluding Pelvic Lymph Node (PLN) Metastasis < 2 mm
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Detection of Distant Metastasis of Vidoflufolastat (18F) Scan - Participants With at Least One Distant Metastatic Lesion (%)
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Overview of Adverse Events
timeFrame: Adverse Events are reported from the single dose of study treatment administration until 14 days afterwards, for a maximum time frame of approx. 14 days.
measure: Vidoflufolastat (18F) Scan Inter-reader Variability - %
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Vidoflufolastat (18F) Scan Inter-reader Variability - Number of Scans Agreed
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Vidoflufolastat (18F) Scan Intra-reader Variability
timeFrame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan
measure: Observed Maximum Blood Concentration (Cmax) of Vidoflufolastat (18F)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
measure: Time of Maximum Observed Blood Concentration Occurrence (Tmax) of Vidoflufolastat (18F)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
measure: Area Under the Vidoflufolastat (18F) Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
measure: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of Vidoflufolastat (18F)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Half-Life Lambda z of Vidoflufolastat (18F)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
measure: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of Vidoflufolastat (18F)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
measure: Urinary Excretion of Radioactivity Expressed as a Percentage of Injected Activity (%IA) of Vidoflufolastat (18F)
timeFrame: Day 1 (pre-injection/0 hour, 0 hour (injection) - T (image acquisition starting time), T (image acquisition starting time) to 3 hours, 3 hours to 5 hours post imaging)
measure: Total Systemic Clearance for Intravenous Administration (CL) of Vidoflufolastat (18F)
timeFrame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Explorer Molecular Imaging center
state: California
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nimes Cedex 9
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Toulouse 4
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Bellinzona
country: Switzerland
facility: Novartis Investigative Site
city: Geneve 14
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: