Study of Diagnostic Performance of [18F]CTT1057 in BCR: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Diagnostic Performance of [18F]CTT1057 in BCR (NCT04838613), a na phase 3 study. The primary outcome is Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F).

2. Clinical Question

The study concerns people with prostate cancer and rising PSA levels indicating biochemical recurrence. Its diagnostic question is whether [18F]CTT1057 PET imaging can detect and localize PSMA-positive findings when assessed against a Composite Truth Standard (CTS). The registry record describes the primary measure as a region-level correct localization rate, rather than a measure of patient survival or treatment response.

The investigational imaging agent was [18F]CTT1057, also called vidoflufolastat (18F) in the endpoint descriptions. Participants underwent PET/CT imaging with this agent and [68Ga]Ga-PSMA-11, with the sequence assigned at random in a 1:1 ratio. The comparator for the primary diagnostic assessment was the CTS, not simply the other imaging agent. The record says the gallium scan could be part of the CTS if required and also had secondary-outcome roles.

The main question is therefore how often regions identified as PET-positive with [18F]CTT1057 had at least one lesion whose location corresponded exactly with the reference standard. The endpoint counts a region as correctly localized when it contains at least one true-positive lesion, even if there are also false-positive findings in that region. The registry record does not report the observed rate, its confidence interval, or the number of regions evaluated. Consequently, the diagnostic performance cannot be quantified from the record description alone.

The study also listed patient-level sensitivity, specificity, negative predictive value, accuracy, correct detection rate and detection rate, as well as region-level sensitivity and specificity. Their numerical results are not reported in the registry record.

3. Trial Design

This was a Phase III diagnostic imaging study, listed as completed, with an enrollment of 190. The brief summary says approximately 190 participants were to be enrolled to ensure at least 152 evaluable participants. Evaluable status required an evaluable [18F]CTT1057 PET/CT scan, at least one evaluable CTS assessment, and no prohibited systemic antineoplastic therapy before completion of the required scans and CTS procedures.

Participants were assigned at random in a 1:1 ratio to one of two PET/CT scan sequences: [18F]CTT1057 followed by [68Ga]Ga-PSMA-11, or the reverse sequence. The record states that the scans were at least 14 days apart. It describes [18F]CTT1057 as the investigational imaging agent and the gallium scan as part of the CTS if required, as well as an imaging procedure with secondary-outcome roles. The complete procedural description for both sequences is not reported in the registry record.

The study is described as sequential, and masking is listed as none. Allocation is listed as not applicable, and the registry cautions that the arms are not a like-for-like control comparison. Thus, the randomized assignment concerns imaging sequence; it should not be read as a randomized comparison of treatment effects or as evidence that one arm represents a conventional control group.

The study began on 2021-09-30, reached primary completion on 2023-11-23, and is listed as completed. The record does not report the number who actually enrolled or were evaluable as separate results. Nor does it provide a numerical primary-endpoint estimate, a confidence interval, or a detailed analysis plan. The posted design information supports a description of the intended diagnostic assessment, but not a conclusion about the observed accuracy of the imaging agent.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Prior to participation in the study, patients had to have biopsy proven prostate adenocarcinoma and diagnosis of biochemical recurrence following initial definitive therapy with either radical prostatectomy or curative intent radiation therapy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Efficacy Analysis Set (EFF) included all randomized participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan imaging and at least one evaluable CTS assessment, and did not receive any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures. Baseline PSA levels were unavailable for 4 of the 161 participants in the EFF set.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The Full Analysis Set includes all randomized participants. Per protocol, two PET/CT scans were performed at least 2 weeks apart to ensure a clean safety profile assessment for each PET radiopharmaceutical. Participants were randomly assigned (1:1 ratio) to one of two scan sequences to counter-balance any potential change in lesions between the 2 scans: 1. \[18F\]CTT1057 followed by \[68Ga\]Ga-PSMA-11 2. \[68Ga\]Ga-PSMA-11 followed by \[18F\]CTT1057 Study was not intended to compare the two sequences.

6. Primary Endpoint

The registry lists the primary outcome as Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F), measured over 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).

The primary endpoint is the region-level correct localization rate (CLR) of vidoflufolastat (18F), expressed as a percentage of regions. It is defined as the percentage of regions containing at least one true-positive lesion with an exactly localized correspondence between PET imaging and the reference standard, among all regions containing at least one PET-positive finding. A region with a true-positive lesion remains counted as correctly localized even if a false-positive finding is also present in that same region.

This is a localization measure, not a count of all lesions detected and not a patient-level measure. Its denominator is restricted to regions with at least one PET-positive finding. It therefore addresses whether positive imaging findings correspond in location to the CTS, rather than how often the scan identifies disease across every region in every participant. The distinction matters: a region-level result cannot by itself describe the probability that an individual patient has disease, and the endpoint definition does not make it a measure of specificity.

The endpoint uses the CTS as the reference and allows that assessment to be obtained within 8 weeks before or after the [18F]CTT1057 PET scan, or during follow-up up to 90 days after radiotherapy for PSA level assessment. The registry record does not report the observed CLR, its confidence interval, or the evaluated region counts. The rationale for selecting this endpoint beyond its stated focus on correct localization is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is sufficient to explain the endpoint structure and some design features, but not to reconstruct the primary analysis. The result estimate, its confidence interval, the number of analyzed regions, and the detailed statistical analysis plan are not reported in the registry record.

What the endpoint counts

The endpoint is a percentage of regions. Its numerator is defined through regions containing at least one true-positive lesion with an exactly localized match between PET imaging and the CTS. Its denominator is all regions with at least one PET-positive finding. The definition allows a region containing both true-positive and false-positive findings to qualify as correctly localized, provided it contains at least one true-positive lesion. This is a region-level rule; it does not count each lesion as an independent unit in the endpoint definition.

General statistical explanation: a proportion is interpreted by considering both its numerator and denominator. A percentage based on a limited number of assessed units can be less precise than one based on a larger number, even when the point estimates are similar. The registry record does not report the numerator or denominator for CLR, so its precision cannot be assessed from the endpoint description.

Reference standard and timing

The CTS is the reference standard for the primary localization assessment. The registry allows CTS information obtained within 8 weeks before or after the [18F]CTT1057 PET scan, or during follow-up up to 90 days after radiotherapy for PSA level assessment. A reference standard collected at a different time can affect how well a finding represents the state at imaging; the registry description does not report how timing was handled in the analysis or how many assessments came from each permitted period.

The record says the gallium scan could be part of the CTS if required and was also used in the imaging sequence. It does not fully describe the CTS components or the rules used to combine them. The detailed adjudication procedures, handling of disagreements, and any blinding of assessors to imaging results are not reported in the registry record.

Confidence intervals and tests

The primary outcome specifies a 95% confidence interval. General statistical explanation: a confidence interval expresses uncertainty about the estimate, based on a statistical method and its assumptions. It should be read alongside the point estimate and the number of observations contributing to it. Since neither the estimate nor the interval is reported, no precision judgment can be made. The registry record also does not report a primary-endpoint p-value or the method used to calculate the interval.

The record lists 18 outcome measures and zero analyses. This does not establish that no analyses were performed; it means that an analysis count is not reported in the available registry information. Statistical methods for secondary outcomes, covariate adjustment, subgroup analyses, handling of multiple assessments per participant, and any model-based uncertainty estimates are not reported in the registry record.

Sequence assignment and planning

The scan sequence was randomized in a 1:1 ratio, but the registry explicitly cautions that the arms are not a like-for-like control comparison. The sequence assignment should therefore be distinguished from the primary endpoint assessment against the CTS. The record does not report a statistical model for evaluating sequence effects or a comparison of sequence groups.

The registry includes planning assumptions for a separate sample-size illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect stated as a fraction of the observed effect. These assumptions describe an illustration based on an observed effect, not the trial's own design justification. The record does not report the original sample-size justification or the numerical planning outputs. Such planning illustrations are not observed power and do not replace the trial's actual endpoint estimate or uncertainty.

Over-dispersion and clustering

General statistical explanation: when observations vary more than a simple statistical model assumes, uncertainty can be understated; this is often described as over-dispersion. Diagnostic data can also include multiple regions from the same participant, which may be statistically related rather than independent. The endpoint is region-level, but the registry record does not report whether the analysis accounted for within-participant clustering or assessed over-dispersion. No model details are available to determine how these issues were addressed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including the region-level primary CLR and several patient-level and region-level secondary diagnostic measures. It records zero analyses, and does not report a multiplicity strategy. The registry record therefore does not state whether the primary endpoint was treated as a single confirmatory test, whether secondary outcomes were considered exploratory, or whether any adjustment was applied when interpreting multiple outcomes. Without a reported analysis plan and results, the chance of false-positive findings across multiple tests cannot be assessed.

The brief summary describes a planned evaluable population of at least 152 participants. Evaluable participants were to have an evaluable [18F]CTT1057 PET/CT scan, at least one evaluable CTS assessment, and no prohibited systemic antineoplastic therapy before completion of the required imaging and CTS procedures. The primary endpoint description also defines the Efficacy Analysis Set as randomized participants meeting specified imaging, CTS, treatment receipt, and therapy criteria, but its description is incomplete in the registry record.

The number of participants who met these criteria is not reported in the registry record. Neither are the number excluded, reasons for exclusion, missing or unevaluable scans, missing CTS assessments, or the handling of incomplete data. The record does not report whether any imputation, sensitivity analysis, or alternative analysis population was used. It also does not report whether the endpoint analysis used only participants with complete reference assessments or addressed regions that could not be classified.

These omissions matter because diagnostic estimates depend on which participants, assessments and regions contribute to the analysis. The target of approximately 190 enrolled participants and at least 152 evaluable participants is a planning description, not a report of the final analysis population. The completed status does not resolve the missingness or multiplicity information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (0.6%).

The safety record lists serious adverse events for the [18F]CTT1057 group and the Gallium (68Ga) Gozetotide group. For [18F]CTT1057, 171 participants were at risk and 1 was affected by a serious adverse event. For Gallium (68Ga) Gozetotide, 178 participants were at risk and 0 were affected by a serious adverse event. Deaths are listed as 0 in both groups.

The record also lists other adverse events in 20 of 171 participants in the [18F]CTT1057 group and 16 of 178 participants in the Gallium (68Ga) Gozetotide group. These are counts, not adjusted comparisons. The registry cautions that the arms are not a like-for-like control comparison, and the scan sequences were randomized rather than representing a straightforward treatment-control design. The figures should not be interpreted as establishing a safety difference between agents.

Dyspnoea at 0.6% is listed among the top serious adverse event terms. The record does not specify in that listing which group the term belongs to or provide further event-level context. The counts alone do not describe severity gradations, timing, causality assessment, or the duration of observation. No causal conclusion should be drawn from these figures in isolation.

12. What the Result Does, and Does Not, Mean

The registry record describes a completed Phase III diagnostic imaging study of [18F]CTT1057 in people with prostate cancer and rising PSA levels associated with biochemical recurrence. It specifies a primary endpoint designed to measure correct localization of PET-positive regions against a Composite Truth Standard. It also lists additional patient-level and region-level diagnostic outcomes.

However, the primary endpoint result is not reported in the registry record. The numerical CLR, its 95% confidence interval, and the number of regions contributing to the analysis are absent. Numerical results for the listed secondary outcomes are also not reported. As a result, the record does not establish the size or precision of the observed diagnostic performance. It cannot support a conclusion about the frequency of correctly localized findings or how uncertain that estimate was.

The endpoint definition is important to the scope of any interpretation. It assesses localization among regions with a PET-positive finding and counts a region as correctly localized when it contains at least one true-positive lesion, even if there are false-positive findings in the same region. It is not equivalent to patient-level sensitivity, specificity, or accuracy. Those are separate outcomes and their results are not reported either.

The record's completed status indicates that the study is listed as finished, but completion is not a substitute for posted outcome estimates. Nor does the sequence assignment make the two groups a conventional control comparison: the registry explicitly cautions against treating the arms as like-for-like. The central comparison for CLR is with the CTS.

The safety figures are counts within the listed groups. They do not, on their own, establish causation or a comparative safety effect. Overall, the record supports a description of the intended diagnostic question, endpoint, and study structure. It does not provide enough numerical outcome information to quantify the primary diagnostic result or assess its statistical precision.

13. Why This Trial Matters Statistically

This study is statistically notable for using a region-level localization endpoint rather than relying only on a patient-level classification. That choice focuses the question on whether positive imaging findings correspond to the location identified by a reference standard. It also makes the unit of analysis important: several regions may be assessed within a participant, and the registry record does not report whether the statistical analysis accounted for possible dependence among those regions.

The endpoint's denominator is defined only among regions with at least one PET-positive finding. This makes the measure different from a measure that includes all regions, and its interpretation depends on the stated rule that a region with at least one true-positive lesion counts as correctly localized even if false-positive findings coexist there. Understanding that rule is necessary before interpreting any future numerical estimate.

The sequential imaging design also calls attention to the distinction between randomized order and a randomized treatment comparison. The two scan sequences were assigned at random in a 1:1 ratio, but the registry warns that the arms are not a like-for-like control comparison. The primary diagnostic assessment is against the CTS, so sequence assignment should not be mistaken for evidence of comparative efficacy.

Finally, the record illustrates why endpoint definitions and study status are not enough to interpret diagnostic evidence. Although the study is listed as completed and specifies a 95% confidence interval for its primary measure, the result and interval are not reported. Without them, readers cannot evaluate either the magnitude or the precision of the observed localization rate. The statistical importance of the design is clear, but the registry information does not supply the outcome evidence needed for a quantitative interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation of the registry record is that it does not report the primary endpoint estimate, its 95% confidence interval, or the number of analyzed regions. The listed secondary diagnostic outcomes likewise have no numerical results in the record information available for interpretation. This prevents assessment of the observed result and its precision.

The analysis description is incomplete. The record does not report how the CTS was assembled, how conflicting reference findings were adjudicated, whether assessors were blinded, or how timing differences between the PET scan and CTS were handled. It allows CTS assessments within 8 weeks before or after imaging or during follow-up up to 90 days after radiotherapy for PSA level assessment, but does not report how many assessments used each timing route.

The registry does not report the final number enrolled, the number meeting the Efficacy Analysis Set criteria, or the number of participants and regions included in the primary analysis. Reasons for missing or unevaluable imaging and reference assessments, and the methods for handling them, are also not reported. The brief summary gives a target of approximately 190 participants and at least 152 evaluable participants, but those targets do not establish the observed analysis population.

The statistical analysis plan is not reported in detail. In particular, the record does not state how uncertainty was calculated, whether clustering of regions within participants was addressed, or how multiplicity across 18 outcome measures was handled. The scan sequence was randomized, but the record cautions that groups are not a like-for-like control comparison and does not report an analysis of sequence effects.

These limitations concern what can be concluded from the registry record; they do not establish that the omitted procedures or analyses were not performed. They mean that the methods and results needed for a full independent statistical appraisal are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Diagnostic Performance of [18F]CTT1057 in BCR — NCT04838613.
• Registry record last updated 2025-10-20; status last verified 2025-10.
• Results first posted 2025-03-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT04838613 is a completed Phase III study evaluating [18F]CTT1057 PET imaging in people with prostate cancer and rising PSA levels associated with biochemical recurrence. The registry lists enrollment of 190 and describes random assignment in a 1:1 ratio to imaging sequences using [18F]CTT1057 and [68Ga]Ga-PSMA-11. Masking is listed as none, and the record cautions that the sequence groups are not a like-for-like control comparison.

The primary endpoint is region-level correct localization rate against a Composite Truth Standard. The endpoint is defined as the percentage of PET-positive regions containing at least one exactly localized true-positive lesion, whether or not a false-positive finding is also present in the region. The record lists a 95% confidence interval but does not report the estimate or interval. It also lists 18 outcome measures and zero analyses. Numerical diagnostic results, detailed analysis methods, multiplicity handling, and missing-data procedures are not reported in the registry record.