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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04838626

Collaborator

(none)

195

Enrollment

Locations

Arm

23.7

Anticipated Duration (Months)

13.9

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms Prostate Cancer	Drug: [18F]CTT1057	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

195 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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.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)

Primary Purpose:

Diagnostic

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

Actual Study Start Date :

Sep 7, 2021

Anticipated Primary Completion Date :

Aug 30, 2023

Anticipated Study Completion Date :

Aug 30, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: PET/CT imaging with [18F]CTT1057

All eligible participants will be enrolled to receive [18F]CTT1057 imaging agent on Day 1 and have PET/CT scan

Drug: [18F]CTT1057

PET/CT imaging with [18F]CTT1057

Other Names:

Single intravenous dose of approximately 370 Mega-Becquerel (MBq) and subsequent PET/CT scan

Outcome Measures

Primary Outcome Measures

Patient-level sensitivity of [18F]CTT1057 [[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]
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.
Region-level specificity of [18F]CTT1057 [[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]
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.

Secondary Outcome Measures

Patient-level specificity of [18F]CTT1057 [[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]
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
Patient-level positive predictive value of [18F]CTT1057 [[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]
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)
Patient-level negative predictive value of [18F]CTT1057 [[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]
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))
Patient-level accuracy of [18F]CTT1057 [[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]
Proportion of patients that are SoT and [18F]CTT1057 positive (TP) and negative (TN) among all patients in EFF (TP+TN+FP+FN)
Region-level sensitivity of [18F]CTT1057 for patients excluding 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]
Sensitivity of [18F]CTT1057 PET imaging in the PLN region, excluding from the analysis those lymph nodes showing metastasis <2mm (micro-metastasis)
Region-level sensitivity of [18F]CTT1057 [[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]
Proportion of PLN regions that test positive on both [18F]CTT1057 and SoT (TP) among those that are SoT positive (TP+FN)
Region-level positive predictive value of [18F]CTT1057 [[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]
Proportion of PLN regions that are SoT and [18F]CTT1057 positive (TP) among those regions that test positive on [18F]CTT1057 (TP+FP)
Region-level negative predictive value of [18F]CTT1057 [[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]
Proportion of PLN regions that are SoT and [18F]CTT1057 negative (TN) among those regions that test negative on [18F]CTT1057 (TN+FN)
Region-level accuracy of [18F]CTT1057 [[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]
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)
Detection of distant metastasis in PS patients [[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]
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.
Characterize the safety and tolerability of [18F]CTT1057 [From first dosing (Day 1) up to 14 days post dosing]
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.
[18F]CTT1057 scan inter-reader variability [[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]
Scan inter-reader variability is defined the agreement rate among reader determination of [18F]CTT1057 images.
[18F]CTT1057 scan intra-reader variability [[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]
Scan intra-reader variability is defined as the within-reader agreement rate of [18F]CTT1057 images.
Observed maximum blood concentration (Cmax) of [18F]CTT1057 [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)]
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.
Time of maximum observed blood concentration occurrence (Tmax) of [18F]CTT1057 [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)]
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.
Area under the [18F]CTT1057 concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)]
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.
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [18F]CTT1057 [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post infusion)]
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.
Terminal elimination half-life (T1/2) of [18F]CTT1057 [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)]
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.
Volume of distribution during the terminal phase following intravenous elimination (Vz) of [18F]CTT1057 [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)]
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.
Total systemic clearance for intravenous administration (CL) of [18F]CTT1057 [Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)]
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.
Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA) of [18F]CTT1057 [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)]
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.
Change in patient management plans attributed to the [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]
Percentage of patients who underwent a change in intended treatment plan attributed to the PET/CT scan as assessed by pre and post imaging questionnaires

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Marseille		France	13273
2	Novartis Investigative Site	Nimes Cedex 9		France	30029
3	Novartis Investigative Site	Pierre Benite Cedex		France	69495
4	Novartis Investigative Site	Toulouse Cedex 9		France	31059
5	Novartis Investigative Site	Bergamo	BG	Italy	24127
6	Novartis Investigative Site	Milano	MI	Italy	20141
7	Novartis Investigative Site	Milano	MI	Italy	20162
8	Novartis Investigative Site	Milano	MI	Italy
9	Novartis Investigative Site	Rozzano	MI	Italy	20089
10	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona	Spain	08907
11	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
12	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
13	Novartis Investigative Site	Bellinzona		Switzerland	6500
14	Novartis Investigative Site	Geneve		Switzerland	1205