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

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ClinicalTrials.gov Identifier: NCT04838613
Recruitment Status : Not yet recruiting
First Posted : April 9, 2021
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

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 to complete the [18F]CTT1057 PET/CT scan procedure (i.e. investigational imaging agent administration and successful completion of the PET/CT scan), which will be required for the calculation of the co-primary endpoints.


Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Prostate Cancer Recurrence Drug: [18F]CTT1057 Drug: [68Ga]Ga-PSMA-11 Phase 3

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 radical prostatectomy or curative-intent radiotherapy, using a Composite Truth Standard (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 (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, inconclusive or negative:

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:

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 at patient level). 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Once eligibility is confirmed, the participants will be 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
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: 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)]
Estimated Study Start Date : August 30, 2021
Estimated Primary Completion Date : April 7, 2023
Estimated Study Completion Date : April 10, 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Region-level correct localization rate (CLR) of [18F]CTT1057 [ Time Frame: [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 correct localization rate (CLR) is defined as the proportion of regions containing at least one True Positive (TP) lesion (anatomically 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 by central assessments. 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).

  2. Patient-level positive predictive value (PPV) (with anatomical localization) of [18F]CTT1057 [ Time Frame: [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) is defined as the proportion of patients who have at least one True Positive (TP) lesion (anatomically 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 by central assessments. 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).


Secondary Outcome Measures :
  1. Patient-level sensitivity of [18F]CTT1057 [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  2. Patient-level specificity of [18F]CTT1057 [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  3. Patient-level negative predictive value of [18F]CTT1057 [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  4. Patient-level accuracy of [18F]CTT1057 [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  5. Patient-level correct detection rate (CDR) [ Time Frame: [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) 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  6. Patient-level detection rate [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  7. Region level sensitivity of [18F]CTT1057 [ Time Frame: [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 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).

  8. Region level specificity of [18F]CTT1057 [ Time Frame: [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 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).

  9. Region level negative predictive value of [18F]CTT1057 [ Time Frame: [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 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).

  10. Region level accuracy of [18F]CTT1057 [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  11. Patient-level positive predictive value related to PSA levels [ Time Frame: [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 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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  12. Incidence of Treatment Emergent Adverse Events [ Time Frame: From first dosing (Day 1) up to 14 days post dosing ]
    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.

  13. [18F]CTT1057 scan inter-reader variability [ Time Frame: [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) ]
    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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  14. [18F]CTT1057 scan intra-reader variability [ Time Frame: [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) ]
    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 post-prostatectomy and patients after prostate radical radiotherapy (RT).

  15. Concordance between [18F]CTT1057 and [68Ga]Ga-PSMA-11 for detection of lesions at patient level using central reads [ Time Frame: [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 positivity at patient level using central reads. 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).

  16. Change in patient management plans attributed to the [18F]CTT1057 PET/CT scan [ Time Frame: From randomization up to 14 days after obtaining the results of the [18F]CTT1057 PET imaging ]
    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 post-prostatectomy and patients after prostate radical radiotherapy (RT).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent must be obtained prior to participation in the study
  • Biopsy proven prostate adenocarcinoma.
  • Biochemical recurrence defined by American Urological Association (AUA) criteria for patients who have undergone radical prostatectomy (detectable or rising PSA value measured 6-13 wk after surgery, that is ≥0.2 ng/mL with a second determination of a PSA level>0.2 ng/mL at least 2 week apart) and by American Society for Radiation Oncology (ASTRO)-Phoenix criteria for patients who have undergone curative-intent radiotherapy (PSA≥2 ng/mL above the nadir).
  • Eastern Cooperative Oncology Group (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 reasons (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 Coronavirus Disease 2019 (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 and current treatment with Luteinizing Hormone-Releasing Hormone (LHRH) analogues
  • Any prior ADT (first or second generation) 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
  • Patients with small cell or neuroendocrine PCa in more than 50% of biopsy tissue

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04838613


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04838613    
Other Study ID Numbers: CAAA405A12301
2020-003959-16 ( EudraCT Number )
First Posted: April 9, 2021    Key Record Dates
Last Update Posted: April 9, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
[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
Additional relevant MeSH terms:
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Prostatic Neoplasms
Recurrence
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Disease Attributes
Pathologic Processes