Study of Diagnostic Performance of [18F]CTT1057 for PSMA-positive Tumors Detection

Study Overview
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Brief Summary
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The purpose of this study is 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) will be used for the histopathology assessments. Approximately 195 participants will be enrolled to ensure that at least 156 participants are evaluable (i.e. have both an evaluable PET/CT scan and histopathology assessment and have not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery), which will be required for the calculation of the co-primary endpoints.

Detailed Description
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This is a multi-center, single-arm, open-label prospective study to evaluate the diagnostic performance of [18F]CTT1057 as a PET imaging agent for detection and localization of PSMA positive tumors, using histopathology as SoT. Tissue specimens from both the primary tumor and pelvic lymph nodes dissected during surgery from patients with newly-diagnosed high-risk PCa will be used for the histopathology assessments. All participants will receive [18F]CTT1057 for PET/CT scan imaging, and surgery (radical prostatectomy and extended pelvic lymph node dissection) will be performed up to 6 weeks after but not sooner than 48 hours after the completion of the [18F]CTT1057 PET/CT scan for pathology assessment of the tissue specimens. The co-primary endpoints of patient-level sensitivity and region-level specificity will be assessed by comparing the central reading results of the [18F]CTT1057 PET scan to the histopathology results in the dissected tissue specimens, i.e. both the primary tumor and the dissected Pelvic Lymph Node (PLN)). Pathology will be assessed by the local pathologists as per Standard of Care (SoC), who will be blinded to the PET data.

Official Title
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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

Conditions
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Prostatic Neoplasms, Prostate Cancer

Intervention / Treatment
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* Drug: [18F]CTT1057


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PET/CT imaging with [18F]CTT1057<br>All eligible participants will be enrolled to receive [18F]CTT1057 imaging agent on Day 1 and have PET/CT scan | Drug: [18F]CTT1057<br>* PET/CT imaging with [18F]CTT1057<br>* Other names: Single intravenous dose of approximately 370 Mega-Becquerel (MBq) and subsequent PET/CT scan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-level sensitivity of [18F]CTT1057 | Sensitivity of [18F]CTT1057 PET imaging, considering PSMA positive patients as those who show at least one pathological [18F]CTT1057 uptake either in the primary tumor and/or metastatic PLN regions, with anatomically localized correspondence with the SoT. | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Region-level specificity of [18F]CTT1057 | Specificity of [18F]CTT1057 PET imaging, defined as proportion of PLN regions that test negative for lymph nodes on [18F]CTT1057 among those that are lymph node negative on the SoT. | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-level specificity of [18F]CTT1057 | Specificity of [18F]CTT1057 PET imaging, considering PSMA negative patients as those who do not show any pathological [18F]CTT1057 uptake either in the primary tumor or PLNs and will be confirmed not having primary tumor or metastatic PLNs with the SoT | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Patient-level positive predictive value of [18F]CTT1057 | Proportion of patients who are both [18F]CTT1057 and SoT positive (true positives (TP) among those who test positive on [18F]CTT1057 (TP+ false positives(FP) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Patient-level negative predictive value of [18F]CTT1057 | Proportion of patients who are both [18F]CTT1057 and SoT negative (true negatives (TN)) among those who test negative on [18F]CTT1057 (TN+ false negatives (FN)) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Patient-level accuracy of [18F]CTT1057 | Proportion of patients that are SoT and [18F]CTT1057 positive (TP) and negative (TN) among all patients in EFF (TP+TN+FP+FN) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Region-level sensitivity of [18F]CTT1057 for patients excluding micro-metastasis | Sensitivity of [18F]CTT1057 PET imaging in the PLN region, excluding from the analysis those lymph nodes showing metastasis <2mm (micro-metastasis) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Region-level sensitivity of [18F]CTT1057 | Proportion of PLN regions that test positive on both [18F]CTT1057 and SoT (TP) among those that are SoT positive (TP+FN) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Region-level positive predictive value of [18F]CTT1057 | Proportion of PLN regions that are SoT and [18F]CTT1057 positive (TP) among those regions that test positive on [18F]CTT1057 (TP+FP) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Region-level negative predictive value of [18F]CTT1057 | Proportion of PLN regions that are SoT and [18F]CTT1057 negative (TN) among those regions that test negative on [18F]CTT1057 (TN+FN) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Region-level accuracy of [18F]CTT1057 | Proportion of PLN regions that are SoT and [18F]CTT1057 positive (TP) and negative (TN) among all PLN regions assessed [18F]CTT1057 (TP+TN+FP+FN) | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Detection of distant metastasis in PS patients | Number of distant metastasis identified at PET/CT scan in all patients, and percentage of patients with at least one distant metastatic lesion (extra-PLN, visceral or skeletal)identified by PET scan in all patients with an evaluable [18F]CTT1057 PET/CT scan. | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Characterize the safety and tolerability of [18F]CTT1057 | The distribution of adverse events (AEs) within 14 days after the administration of [18F]CTT1057 will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. | From first dosing (Day 1) up to 14 days post dosing | 
| [18F]CTT1057 scan inter-reader variability | Scan inter-reader variability is defined the agreement rate among reader determination of [18F]CTT1057 images. | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| [18F]CTT1057 scan intra-reader variability | Scan intra-reader variability is defined as the within-reader agreement rate of [18F]CTT1057 images. | [18F]CTT1057 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from [18F]CTT1057 scan | 
| Observed maximum blood concentration (Cmax) of [18F]CTT1057 | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. Cmax will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | 
| Time of maximum observed blood concentration occurrence (Tmax) of [18F]CTT1057 | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. Tmax will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | 
| Area under the [18F]CTT1057 concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. AUClast will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | 
| Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [18F]CTT1057 | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. AUCinf will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post infusion) | 
| Terminal elimination half-life (T1/2) of [18F]CTT1057 | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. The half-life will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | 
| Volume of distribution during the terminal phase following intravenous elimination (Vz) of [18F]CTT1057 | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. Vz will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | 
| Total systemic clearance for intravenous administration (CL) of [18F]CTT1057 | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization in a subset of approximately 10 patients. CL will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | 
| Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA) of [18F]CTT1057 | Urine samples will be collected over specified time intervals and analyzed for radioactivity in a subset of approximately 10 patients. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCa, [18F]CTT1057, Positron Emission Tomography/Computerized Tomography, PET/CT, Radioligand, Imaging, Primary Staging, PS, Standard of Truth, SoT, Prostate Cancer