This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Next Generation Sequencing-Based Stratification of Front Line Treatment of HighGrade Neuroendocrine Carcinoma (NCT04452292), a non-randomized na study. The primary outcome is Sequencing Rate (Feasibility).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04452292 |
| Phase | NA |
| Condition | Large-Cell Neuroendocrine Carcinoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Charles Kunos |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with metastatic high-grade neuroendocrine carcinoma, excluding small cell carcinoma in its stated hypothesis. The condition listed in the registry is large-cell neuroendocrine carcinoma. The record says two participants were enrolled, but does not present their outcome data because of the possibility that participants could reasonably be identified given the low enrollment.
Intervention
The study evaluated a treatment-stratification approach based on next-generation sequencing and molecularly defined subtypes. One intervention is described as treatment specific for non-small cell carcinoma or adenocarcinoma. The record does not provide the treatment regimen or enough detail to characterize how treatment was delivered to individual participants.
Comparator
The parallel groups are defined by whether the tumor had a TP53/Rb1 co-mutation. The group without that co-mutation is described as non-small cell-like; the group with it has the co-mutation present. The registry also lists treatment for small cell lung cancer as an intervention. This was not a randomized comparison, and the groups are not a like-for-like control comparison.
Primary question
The primary feasibility question was what percentage of patients could be sequenced within 2 months of the initial medical oncology visit. The study hypothesis was that mutational analysis could segregate high-grade neuroendocrine carcinoma subtypes and that sequencing-based treatment assignment would be feasible, with potential to improve outcomes. The registry does not present the primary outcome data, so it does not answer the feasibility question.
3. Trial Design
PRECISION-NEC is described as a single-center, open-label pilot feasibility study of molecularly defined subtypes of metastatic high-grade neuroendocrine carcinoma. The registry lists the study phase as NA, allocation as non-randomized, masking as none, and the model as parallel. The study is marked completed.
The two parallel groups are distinguished by the tumor’s TP53/Rb1 co-mutation status. The arm without the co-mutation is characterized as non-small cell-like, and the arm with the co-mutation is characterized by its presence. The listed interventions are treatment specific for non-small cell carcinoma or adenocarcinoma and treatment for small cell lung cancer. The record does not detail specific drugs, treatment schedules, or the clinical process used to assign treatment.
The registry reports enrollment of two participants. Its primary outcome description says data cannot be presented because the low enrollment could make participants reasonably identifiable. The record lists a start date of 2021-09-14 and primary completion date of 2022-05-04. It does not report a sample-size justification or explain how enrollment was selected.
Because allocation was not randomized, the molecular groups should not be treated as exchangeable treatment arms. Any differences between them could reflect their defining tumor characteristics or other factors, rather than a treatment effect. The record itself cautions that the arms are not a like-for-like control comparison. It does not report an analysis comparing the groups.
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.
Overall Study
| Stage | No TP53/Rb1 Co-Mutation | TP53/Rb1 Co-Mutation Present |
|---|---|---|
| STARTED | 2 | 0 |
| COMPLETED | 2 | 0 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Two participants were enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.
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: Closed to slow accrual and no participants were enrolled in TP53/Rb1 Co-Mutation Present arm
| Characteristic | Unit | No TP53/Rb1 Co-Mutation | TP53/Rb1 Co-Mutation Present | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 0 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 0 | 2 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 2 | 0 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 0 | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 2 | — | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Sequencing Rate (Feasibility), measured over 2 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is sequencing rate, described as the percentage of patients able to be sequenced within 2 months of the initial medical oncology visit. It is a feasibility measure: it asks whether the sequencing step can be completed within the specified clinical timeframe. It does not directly measure tumor response, progression, survival, or the benefit of one treatment relative to another.
Feasibility outcomes are useful in a pilot because an approach that depends on molecular testing must be implementable before its clinical consequences can be evaluated. A stated timeframe makes the measure clinically anchored, while the percentage expresses how often the defined process was completed among the relevant participants. Interpreting that percentage requires the observed number sequenced and the denominator used for the calculation.
The registry says the primary data cannot be presented because the two participants enrolled could reasonably be identified due to low enrollment. Consequently, the posted record does not give the sequencing percentage or its underlying counts. It is not possible to determine from the registry whether sequencing was completed for either participant, or whether the 2-month target was met.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central limitation for interpretation is that the registry does not present the primary feasibility result. Although it defines sequencing rate and its timeframe, it gives no observed percentage, count sequenced, or denominator for that outcome. The stated reason is that low enrollment could permit participants to be identified. Therefore, the registry record does not establish whether sequencing was completed within 2 months of the initial medical oncology visit.
The study enrolled two participants and is marked completed, but completion of a study is not itself evidence that its feasibility objective was met. Nor can enrollment alone establish whether the sequencing and treatment-stratification process was workable. The information needed to assess those questions is not reported in the registry record.
The registry lists secondary outcomes of progression-free survival, complete response rate, partial response rate, progressive disease rate, and stable disease rate. It does not present results for these outcomes. No treatment effects, response rates, or time-to-event estimates can be interpreted from the posted information. The record also has no analyses recorded. Without outcome estimates and measures of precision, readers cannot assess the direction or uncertainty of any clinical outcome.
The molecularly defined groups are not randomized comparators. Their tumor mutation status defines the groups and is linked to the treatment strategy under study. The groups therefore cannot be read as if they were otherwise comparable populations receiving alternate treatments. The registry cautions that the arms are not a like-for-like control comparison; it does not report an adjusted or unadjusted comparison that would address this concern.
The adverse-event group entries report zero at risk and zero affected for serious and other adverse events, and zero deaths. Because the listed at-risk counts are zero, these entries do not provide an interpretable estimate of event frequency among participants. They should not be taken as evidence that adverse events did not occur. The record does not present participant-level safety data or explain how these entries relate to the enrolled participants.
Overall, the posted results are insufficient to quantify feasibility, clinical outcomes, or safety. This is a limitation of what the registry reports, not a basis for concluding that the study process succeeded or failed.
9. Statistical Methods Explained
What does a feasibility endpoint measure?
In general, a feasibility endpoint evaluates whether a research process can be carried out as planned, rather than whether a treatment improves a clinical outcome. Here, the stated process is sequencing within 2 months of the initial medical oncology visit. A sequencing rate would describe the proportion of eligible participants for whom sequencing was completed within that timeframe. The registry does not publish the observed rate or the counts needed to interpret it.
In general, a percentage depends on a clearly defined numerator and denominator. The numerator would need to specify which participants met the sequencing criterion, and the denominator would need to identify the participants included in the calculation. The registry outcome description does not give these values. It also does not report how missing or unsuccessful sequencing attempts would be classified.
Why does non-random allocation matter?
In general, random allocation can help balance measured and unmeasured prognostic factors across treatment groups. This study is listed as non-randomized, and its groups are defined by TP53/Rb1 co-mutation status. The record characterizes the group without the co-mutation as non-small cell-like and the group with the co-mutation as co-mutated. Because group membership reflects tumor biology, the groups may differ in ways relevant to outcomes. A direct difference between them would not isolate a causal treatment effect.
The registry lists a parallel model, but parallel groups do not by themselves make a comparison randomized or controlled. The record explicitly cautions that the arms are not a like-for-like control comparison. It does not report adjustment methods, covariate balance, or a statistical analysis comparing the groups. Those omissions limit what can be inferred beyond the descriptive design.
What can be concluded from the posted analyses?
The registry records no analyses. It also withholds the primary outcome data because the low enrollment could make participants reasonably identifiable. The secondary outcomes are named but their results are not presented. In general, an outcome label describes what was intended to be assessed, not the value observed. Without estimates, denominators, and measures of uncertainty, neither the magnitude nor the precision of an outcome can be evaluated.
In general, confidence intervals describe the range of values compatible with an estimate under a specified statistical model and its assumptions. They help distinguish a precise estimate from one that remains uncertain. No outcome estimates or confidence intervals are reported in the registry record, so the precision of the feasibility or clinical outcomes cannot be assessed.
How should planning calculations be understood?
The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a fraction of the observed effect. For time-to-event outcomes, the stated planning quantities concern the total number of events; for other outcomes, they concern participants per arm. These assumptions describe planning calculations, not the design used to conduct this pilot.
In general, a sample-size calculation estimates the amount of information needed to detect a specified effect under stated assumptions. A calculation based on an observed effect is particularly sensitive to that effect estimate; when the estimate is unstable or unavailable, planning values should not be mistaken for a reliable target. Such calculations are not observed power and do not show that the study had adequate power. The registry does not report the effect estimate used in the illustration or the resulting planning values in the trial information summarized in its outcome record. It also does not report the trial’s own sample-size justification.
In general, over-dispersion occurs when outcome variability exceeds what a statistical model assumes. Accounting for it can affect standard errors and the precision of estimates. The registry record does not identify an over-dispersion model or other outcome-specific statistical methods. This general concept therefore does not describe a reported analysis for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists progression-free survival, complete response rate, partial response rate, progressive disease rate, and stable disease rate as secondary outcomes, in addition to the primary sequencing-rate endpoint. When several outcomes are assessed, multiplicity can matter: in general, repeated statistical testing can increase the chance of finding an apparently notable result by chance. Researchers may address this through prespecified outcome priorities or statistical adjustments, but the registry record does not report a multiplicity strategy.
No analyses are recorded, and the registry does not present results for the primary or secondary outcomes. It is therefore not possible to determine whether any adjustment was used in practice or to evaluate the results of multiple outcome tests. The record also does not report a statistical analysis plan, interim analyses, or a prespecified hierarchy for the secondary outcomes.
The registry does not report how missing outcome data were handled, how participants with incomplete sequencing were classified, or which analysis populations were used. These details matter even for a feasibility endpoint: excluding participants without completed sequencing, for example, would answer a different question from including all enrolled participants in the denominator. No such rule can be inferred from the outcome description.
The two participants enrolled are the only enrollment count stated, and primary outcome data are withheld because participants could reasonably be identified. As a result, neither missing-data handling nor analysis-population choices can be evaluated from posted results. These are unreported aspects of the registry record, not evidence about what procedures may have been used outside the record.
11. What the Result Does, and Does Not, Mean
The study’s stated aim was to assess whether next-generation sequencing could be used to stratify front-line treatment according to molecularly defined subtypes of metastatic high-grade neuroendocrine carcinoma. Its primary endpoint was designed to describe sequencing feasibility within 2 months of the initial medical oncology visit. The registry record does not provide the primary outcome data, so it does not show whether the sequencing target was reached.
The study’s hypothesis that mutation analysis could segregate subtypes and that sequencing-based treatment assignment would be feasible is a rationale for the investigation, not a result. The record does not report findings that establish whether the hypothesis was supported. It also does not present the listed response or progression outcomes. No conclusion about clinical benefit or lack of benefit follows from the information posted.
The non-randomized molecular groups are not a conventional controlled treatment comparison. The mutation status used to define the arms also reflects the biological grouping under study, and the record explicitly says the arms are not a like-for-like control comparison. Any comparison between them would need careful interpretation even if outcome estimates were available.
The study is marked completed, but the status does not substitute for outcome reporting. The registry’s reason for withholding primary data is the potential identifiability of participants in a low-enrollment study. That protects against overinterpreting absent data: missing results cannot be treated as favorable, unfavorable, or evidence of no effect. The defensible conclusion is limited to the design and the fact that the posted record does not allow the feasibility, efficacy, or safety questions to be answered.
12. Why This Trial Matters Statistically
This trial is statistically notable because it connects a molecular classification strategy to a practical implementation question. Sequencing-based treatment assignment depends not only on whether tumors can be classified, but also on whether the sequencing step can be completed within the specified clinical timeframe. A feasibility endpoint can therefore identify an operational requirement that would need to be understood before larger outcome evaluations.
The study also illustrates why a molecularly defined group is not automatically a valid control group. Here, TP53/Rb1 co-mutation status defines the parallel arms, and the registry warns that the arms are not like-for-like comparators. The resulting design can describe a treatment-stratification approach, but it does not have the protections of randomized allocation for attributing outcome differences to treatment.
Its very limited enrollment and the decision not to present primary data create a second statistical lesson: privacy constraints can prevent reporting the very quantities needed to judge feasibility. Without a reported numerator, denominator, and estimate, the feasibility endpoint cannot be interpreted, regardless of how clearly it was defined.
Finally, the registry distinguishes a completed pilot from an informative comparative trial. Its design and outcomes indicate what the investigators intended to study, while the absence of outcome analyses prevents conclusions about precision, clinical outcomes, or the performance of the stratification strategy. That boundary is important when interpreting pilot studies and registry records.
13. 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 most consequential trial-specific limitation is that the registry does not present the primary outcome data. It explains that the low enrollment could make participants reasonably identifiable. Without the sequencing result, the stated feasibility endpoint cannot be quantified or assessed against its 2-month timeframe.
Enrollment was two participants. This is the only enrollment count reported, and it emphasizes how little outcome information can be made public in this record. The sample-size justification is not reported in the registry record. The study is a pilot feasibility study, and the record does not establish that it was designed to estimate clinical outcomes precisely or compare treatments.
The non-randomized, mutation-defined arms do not form a like-for-like control comparison. Mutation status is central to the stratification question, but it also means that contrasts between arms may reflect differences associated with tumor subtype. The record does not report adjustments or analyses that might characterize those differences.
Specific treatment regimens and the process of assigning individual treatments are not reported in the registry record. Statistical methods for secondary outcomes, missing data, and analysis populations are also not reported. Although safety entries are present, their at-risk counts are zero, so they do not permit an interpretable assessment of adverse-event frequency among participants.
Finally, no analyses are recorded and no primary or secondary outcome estimates are presented. These limits mean the registry supports description of the intended design, but not assessment of its clinical results or the statistical precision of those results.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Next Generation Sequencing-Based Stratification of Front Line Treatment of HighGrade Neuroendocrine Carcinoma — NCT04452292.
- Registry record last updated 2023-05-17; status last verified 2023-04.
- Results first posted 2023-05-17.
- 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.
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17. Record Summary
The registry describes a completed, single-center, open-label, non-randomized pilot feasibility study of next-generation sequencing-based treatment stratification for metastatic high-grade neuroendocrine carcinoma. It lists a parallel model and groups defined by TP53/Rb1 co-mutation status. The primary endpoint is the percentage of patients sequenced within 2 months of the initial medical oncology visit.
The record reports enrollment of two participants and states that primary outcome data cannot be presented because participants could reasonably be identifiable given low enrollment. Secondary outcomes include progression-free survival and response or disease-status rates, but results are not presented. No analyses are recorded. The posted information therefore describes the study question and design but does not establish sequencing feasibility, clinical outcomes, or safety.