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

Prostate Cancer Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04838626
• Other study ID #: CAAA405A12302
• Secondary ID: 2020-003958-67
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 7, 2021
• Est. completion date: November 24, 2023

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: November 24, 2023
• Est. primary completion date: November 24, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• [18F]CTT1057
PET/CT imaging with [18F]CTT1057

Locations

Country	Name	City	State
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nimes Cedex 9
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Toulouse 4
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Switzerland	Novartis Investigative Site	Bellinzona
Switzerland	Novartis Investigative Site	Geneve
United States	Explorer Molecular Imaging center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	[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
Secondary	[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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)