Study of Diagnostic Performance of [18F]CTT1057 in BCR

NCT04838613 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CAAA405A123012020-003959-16
• Study Type: interventional
• Target: 190
• Locations: 4 countries
• Sites: 13

Brief Summary

The current study aimed at evaluating the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of Prostate specific membrane antigen (PSMA) positivity in patients diagnosed of biochemical recurrence of prostate cancer (PCa), using a composite truth standard. Approximately 190 participants were to be enrolled to ensure at least 152 participants were evaluable (i.e. have both an evaluable \[18F\]CTT1057 Positron emission tomography/Computed Tomography (PET/CT) scan imaging and at least one evaluable Composite Truth Standard (CTS) assessment and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures, which were required for the calculation of the co-primary endpoints.

Conditions

Prostatic Neoplasms; Prostate Cancer; Recurrence

Keywords

[18F]CTT1057; [68Ga]Ga-PSMA-11; Positron Emission Tomography/Computerized Tomography; PET/CT; Radioligand; Imaging; Biochemical recurrence; BCR; Composite Truth Standard; CTS; Prostate Cancer; PCa

Outcome Measures

Primary Outcomes (2)

• Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F)

  Region-level correct localization rate (CLR) is defined as the percentage 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.

  vidoflufolastat (18F) 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 Vidoflufolastat (18F)

  Patient-level positive predictive value (PPV) is defined as the percentage of participants 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 participants who are PET/CT scan positive.

  vidoflufolastat (18F) 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 Outcomes (16)

• Patient-level Sensitivity of Vidoflufolastat (18F)

  vidoflufolastat (18F) 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 Vidoflufolastat (18F)

  vidoflufolastat (18F) 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 (NPV) of Vidoflufolastat (18F)

  vidoflufolastat (18F) 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 Vidoflufolastat (18F)

  vidoflufolastat (18F) 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)

  vidoflufolastat (18F) 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)

Study Arms (1)

PET/CT imaging with [18F]CTT1057 followed by [68Ga]Ga-PSMA-11 or vice versa

EXPERIMENTAL

All eligible participants were 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; Drug: [68Ga]Ga-PSMA-11

Interventions

[18F]CTT1057 DRUG

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

PET/CT imaging with [18F]CTT1057 followed by [68Ga]Ga-PSMA-11 or vice versa

[68Ga]Ga-PSMA-11 DRUG

Single intravenous dose of approximately 150 MBq and subsequent PET/CT scan

PET/CT imaging with [18F]CTT1057 followed by [68Ga]Ga-PSMA-11 or vice versa

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Explorer Molecular Imaging center

Sacramento, California, 95816, United States

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Nîmes, 30029, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Saint-Priest-en-Jarez, 42270, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The participant cohort was mainly European and White, with only one site initiated in the USA. Furthermore, low participant numbers in some subgroups (i.e. participants with prior curative radiation therapy (RT) and participants with baseline Prostate-specific antigen (PSA) levels \>1 ng/mL) precluded interpretation of subgroup analyses. In addition, Composite Truth Standard (CTS) Level 1 (histopathology) was only usable from a very small proportion of patients in this study.

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Once eligibility was confirmed, the participants were randomized in IRT to 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

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 9, 2021
• Study Start: September 30, 2021
• Primary Completion: November 23, 2023
• Study Completion: November 23, 2023
• Last Updated: October 20, 2025
• Results First Posted: March 12, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1); ES (5); CH (1); FR (6)