Study of Diagnostic Performance of [18F]CTT1057 in BCR (GuidePath)

Phase III Study for Evaluation of the Diagnostic Performance of [18F]CTT1057 PET Imaging in Patients With Prostate Cancer With Rising PSA Levels [Biochemical Recurrence (BCR)]

The current study aims at evaluating the diagnostic performance of [18F]CTT1057 as a PET imaging agent for detection and localization of PSMA positivity in patients diagnosed of biochemical recurrence of prostate cancer (PCa), using a composite truth standard.

Approximately 190 participants will be enrolled to ensure at least 152 participants are evaluable (i.e. have both an evaluable [18F]CTT1057 PET/CT scan imaging, and at least one evaluable CTS assessment and have not received any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures), which will be required for the calculation of the co-primary endpoints.

Study Overview

• Status: Completed
• Conditions: Recurrence; Prostatic Neoplasms; Prostate Cancer
• Intervention / Treatment: Drug: [18F]CTT1057; Drug: [68Ga]Ga-PSMA-11

Detailed Description

This is a prospective, open-label, multi center, single-arm Phase III study to evaluate the diagnostic performance of [18F]CTT1057 as a PET imaging agent for detection and localization of PSMA positive tumors in PCa patients diagnosed with biochemical recurrence (BCR) after initial definitive therapy with either radical prostatectomy (RP) or curative intent radiation therapy (RT), using a CTS as reference.

The CTS to be used as reference will be hierarchical in nature, with 3 levels of Standard of Truth (SoT) procedures, that will be applied as follows:

CTS Level 1: Histopathology if available for the lesion (from prospective biopsy or salvage surgery performed within 8 weeks after the [18F]CTT1057 PET/CT scan); OR in case that histopathology is not available for a lesion, inconclusive or negative (for biopsy only):

CTS Level 2: Imaging diagnostic procedures performed on each patient as clinically indicated per SoC, which must include at least a high resolution CT scan with contrast and a [68Ga]Ga-PSMA-11 PET/CT) performed within 8 weeks (either before or after) the [18F]CTT1057 PET/CT scan. Three-month follow-up imaging (from baseline) will also be used as part of the CTS level 2 in cases where it is clinically required for the diagnosis of particular lesion(s); OR if neither of the two above are feasible or deemed appropriate or they are inconclusive:

CTS Level 3: 50% or greater decline in PSA following radiation therapy (as long as no concomitant androgen deprivation therapy (ADT) is given) as per Prostate Cancer Working Group 3 (PCWG3) criteria.

All participants will undergo 2 PET/CT scans: one with the investigational agent [18F]CTT1057 and another with [68Ga]Ga-PSMA-11 (as a component of the CTS Level 2 and for a secondary endpoint of assessment of concordance between the 2 PET/CT scans for detection of lesions). The 2 PET imaging procedures will be performed at least 14 days apart, and the PET/CT scan sequence for each participant will be assigned at random in a 1:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com

Study Locations

• France
  • Marseille, France, 13273
    • Novartis Investigative Site
  • Marseille Cedex 05, France, 13885
    • Novartis Investigative Site
  • Nimes Cedex 9, France, 30029
    • Novartis Investigative Site
  • Pierre Benite, France, 69495
    • Novartis Investigative Site
  • Saint Etienne, France, 42055
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• Switzerland
  • Geneve, Switzerland, 1205
    • Novartis Investigative Site
• United States
  • California
    • Sacramento, California, United States, 95816
      • Explorer Molecular Imaging center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study
• Biopsy proven prostate adenocarcinoma.
• Biochemical recurrence following initial definitive therapy (with either RP or curative intent radiation therapy) as defined:

by AUA criteria (Cookson et al 2007) for patients who have undergone RP: Initial serum PSA of ≥0.2 ng/ml measured at least 6 weeks after RP with a second confirmatory persistent PSA level of >0.2 ng/ml, or by ASTRO-Phoenix criteria (Roach et al 2006) for patients who have undergone curative-intent radiation therapy (RT): Rise of serum PSA measurement of 2 or more ng/mL above the nadir PSA observed post RT.

• ECOG performance status 0-2
• 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
• Prior major surgery undergone less than 12 weeks prior to screening (with the exception of any surgery related to prostatic cancer)
• Known allergy, hypersensitivity, or intolerance to [18F]CTT1057, [68Ga]Ga-PSMA-11, or to CT contrast
• Prior and current use of PSMA targeted therapies
• Prior ADT (first or second generation), including LHRH analogues (agonists or antagonists), within 9 months before screening
• Any 5-alpha reductase inhibitors within 30 days before screening
• Use of other investigational drugs within 30 days before screening
• Castration-resistant patients
• Patient with small cell or neuroendocrine PCa in more than 50% of biopsy tissue
• Prior salvage surgery or salvage radiation therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PET/CT imaging with [18F]CTT1057 followed by [68Ga]Ga-PSMA-11 or vice versa; All eligible participants will be assigned to one of the following two PET/CT scan sequences at random in a 1:1 ratio: Sequence 1: [18F]CTT1057 on Day 1 (investigational imaging agent of interest) followed by [68Ga]Ga-PSMA-11 at least 14 days apart (as part of CTS if required, and for secondary endpoint); Sequence 2: [68Ga]Ga-PSMA-11 (as part of CTS if required, and for secondary endpoint) on Day 1 followed by [18F]CTT1057 (investigational imaging agent of interest) at least 14 days apart

Drug: [18F]CTT1057; Single intravenous dose of approximately 370 Mega-Becquerel (MBq) and subsequent PET/CT scan; Drug: [68Ga]Ga-PSMA-11; Single intravenous dose of approximately 150 MBq and subsequent PET/CT scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Region-level correct localization rate (CLR) of [18F]CTT1057	Region-level correct localization rate (CLR) is defined as the proportion of regions containing at least one True Positive(TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings within the same region, out of all regions containing at least one PET-positive finding. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level positive predictive value (PPV) (with anatomical localization) of [18F]CTT1057	Patient-level positive predictive value (PPV) is defined as the proportion of patients who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all patients who are PET/CT scan positive. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-level sensitivity of [18F]CTT1057	Patient-level sensitivity is defined as the proportion of patients that test positive on [18F]CTT1057 and CTS (True Positive (TP)) among those that are CTS positive (True Positive (TP) or False Negative (FN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level specificity of [18F]CTT1057	Patient-level specificity is defined as the proportion of patients that test negative on [18F]CTT1057 and CTS (True Negative (TN)) among those that are CTS negative (True Negative (TN) or False Positive (FP)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level negative predictive value of [18F]CTT1057	Patient-level negative predictive value is defined as the proportion of patients who are both [18F]CTT1057 and CTS negative (True Negative (TN)) among those who test negative on [18F]CTT1057 (True Negative (TN) or False Negative (FN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level accuracy of [18F]CTT1057	Patient-level accuracy is defined as the proportion of patients that are CTS and [18F]CTT1057 positive (True Positive (TP)) and negative (True Negative (TN)) among those patients that identified on [18F]CTT1057 (True Positive (TP), True Negative (TN), False Positive (FP) or False Negative (FN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level correct detection rate (CDR)	Patient-level correct detection rate (CDR) is defined as the proportion of patients who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all patients who are scanned. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level detection rate	Patient-level detection rate is defined as the proportion of patients who have at least one PET positive lesion, regardless of True Positive (TP) or False Positive (FP) findings, out of all patients who are scanned. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT).	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Region level sensitivity of [18F]CTT1057	Region level sensitivity is defined as the proportion of regions that test positive on both [18F]CTT1057 and CTS (True Positive (TP)) among those regions that are CTS positive (True Positive (TP) or False Negative (FN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients post-prostatectomy and patients after prostate radical radiotherapy (RT).	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Region level specificity of [18F]CTT1057	Region level specificity is defined as the proportion of regions that test negative on both [18F]CTT1057 and CTS (True Negative (TN)) among those regions that are CTS negative (False Positive (FP) or True Negative (TN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients post-prostatectomy and patients after prostate radical radiotherapy (RT).	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Region level negative predictive value of [18F]CTT1057	Region level negative predictive value is defined as the proportion of regions that are CTS and [18F]CTT1057 negative (True Negative (TN)) among those regions that test negative on [18F]CTT1057 (True Negative (TN) or False Negative (FN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients post-prostatectomy and patients after prostate radical radiotherapy (RT).	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Region level accuracy of [18F]CTT1057	Region level accuracy is defined as the proportion of regions that are CTS and [18F]CTT1057 positive (True Positive (TP)) and negative (True Negative (TN)) among those regions that identified on [18F]CTT1057 (True Positive (TP), True Negative (TN), False Positive (FP) and False Negative (FN)). The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Patient-level positive predictive value related to PSA levels	Patient-level positive predictive value related to PSA levels is defined as the percentage of patients who have at least one True Positive (TP) lesion (exactly anatomically localized correspondence between [18F]CTT1057 PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all patients who are [18F]CTT1057 positive, stratified by PSA levels. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Characterize the safety and tolerability of [18F]CTT1057	The distribution of adverse events (AEs) within 14 days after each PET tracer administration 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	Inter-reader variability is defined as the agreement among three readers determination of [18F]CTT1057 images. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
[18F]CTT1057 scan intra-reader variability	Intra-reader variability is defined as the within-reader agreement for two different time points of [18F]CTT1057 images. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT)	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Concordance between [18F]CTT1057 and [68Ga]Ga-PSMA-11 for detection of lesions at lesion level using central reads	Concordance between [18F]CTT1057 and [68Ga]Ga-PSMA-11 for detection of detection of PSMA-positive lesions (location and number) using central reads. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT).	[18F]CTT1057 PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)
Change in patient management plans attributed to the [18F]CTT1057 PET/CT scan	Change in patient management plans attributed to the PET/CT scan is defined as the percentage of patients who underwent a change in intended treatment plan attributed to the [18F]CTT1057 PET/CT scan as assessed by pre and post imaging questionnaires. The endpoint will be analyzed overall in the Efficacy Analysis Set (EFF population) and in each of the following subgroups: Patients with prior Radical Prostatectomy and patients with prior curative intent Radiation Therapy (RT).	From randomization up to 14 days after obtaining the results of the [18F]CTT1057 PET imaging

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): November 23, 2023
• Study Completion (Actual): November 23, 2023

Study Registration Dates

• First Submitted: April 7, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Imaging; PET/CT; Prostate Cancer; BCR; Biochemical recurrence; [18F]CTT1057; Positron Emission Tomography/Computerized Tomography; Radioligand; PCa; CTS; [68Ga]Ga-PSMA-11; Composite Truth Standard
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Gallium 68 PSMA-11
• Other Study ID Numbers: CAAA405A12301; 2020-003959-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No