A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma (NCT02994251), a na phase 2 study. The primary outcome is Progression-free Survival.

2. Clinical Question

3. Trial Design

This was a Phase II, single-center, single-arm study of gemcitabine and cisplatin in combination with conventional TACE for advanced intrahepatic cholangiocarcinoma. Yale University is listed as the sponsor. The record lists allocation as NA, masking as none, and the model as single group. Accordingly, the intended evaluation was of one treatment combination rather than a randomized comparison against a control group.

The record lists an enrollment of 1 and a status of terminated. The study start date is 2017-06-21, and the primary completion date is 2018-11-06. The brief description states a plan to enroll 25 patients over 2 years, with an additional 1.5 years of patient follow-up. That plan differs from the recorded enrollment. The reason for termination is not reported in the registry record; the primary outcome description does state that termination occurred after 1 participant was enrolled and that outcome reporting was limited to protect confidentiality.

The intervention combined two systemic chemotherapy drugs, gemcitabine and cisplatin, with cTACE using doxorubicin or mitomycin-C. The primary objective concerned PFS at 12 months. Secondary outcomes included overall survival, overall time to progression, time to untreatable progression, toxicities assessed using CTCAE Version 4.0, and correlations between changes in dynamic contrast-enhanced MRI and PFS or overall survival. The registry record lists no analyses for these outcomes.

Because the record describes one group and no comparator, it cannot support a treatment effect estimate based on between-group differences. Nor does the planned enrollment describe the number who actually contributed to outcome analyses: the record lists 1 enrolled and 0 analyzed for the primary outcome.

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

Analysis population for the primary outcome, as defined in the registry: Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.

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: Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival, measured over 12 months.

The primary endpoint was the 12-month progression-free survival rate. It was defined as the percentage of patients alive and free of progression at 12 months from enrollment. Progression was to be assessed radiographically using mRECIST and qEASL, based on an MRI obtained at the interventional radiology clinic visit.

PFS is a time-to-event concept: it concerns how long participants remain alive without documented disease progression. A fixed-time PFS rate expresses the proportion meeting that status at a specified time point. In general, this endpoint can describe both progression and death within one outcome measure, while overall survival focuses on death. The record does not provide a PFS estimate, event count, confidence interval, or participant-level follow-up information, so the endpoint's value and precision cannot be evaluated from the posted results.

The 12-month timeframe is part of the stated primary objective, not evidence that any participant completed that period of follow-up. The registry record lists 0 participants analyzed for the primary outcome. It also notes that 0 was entered as the analyzed count to protect confidentiality after the study was terminated following enrollment of 1 participant. Thus, the endpoint is defined, but no interpretable PFS result is reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on what the study was designed to compare and what outcome information is available. This study is recorded as single-group, with allocation listed as NA and masking listed as none. No randomized control group is described. The primary objective is a 12-month PFS rate, but the registry record reports 0 participants analyzed and no endpoint estimate. The methods below explain the concepts relevant to that objective; they do not imply that a particular analysis was conducted.

What does a fixed-time PFS rate represent?

In general, PFS is a time-to-event outcome that counts progression or death as an event, according to the outcome definition used by a study. A fixed-time rate asks what proportion of participants are alive and progression-free at a specified time point. Here the specified time point is 12 months from enrollment, and the record says disease burden was to be evaluated with mRECIST and qEASL using MRI at the interventional radiology clinic visit.

A fixed-time estimate requires outcome and follow-up information sufficient to determine each participant's status at that time, or a statistical method that accounts for incomplete follow-up. The record does not report individual follow-up, the number of events, censoring, a PFS estimate, or its uncertainty. It is therefore not possible to assess how the endpoint was calculated or how precisely it was estimated. A stated endpoint definition is not the same as a reported endpoint result.

Why does uncertainty matter?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. Its width reflects statistical precision: a wider interval indicates more uncertainty. A point estimate without an interval can conceal substantial uncertainty, particularly when information is sparse. In this record, neither a point estimate nor a confidence interval for PFS is reported, so neither the apparent outcome nor its precision can be assessed.

When few participants contribute information, estimates of proportions or event times may be unstable. That is a general statistical concern, not a numerical conclusion about the participant in this study. The record specifically says that the analyzed count was entered as 0 to protect confidentiality after 1 participant was enrolled. It does not supply enough data to quantify an estimate or its uncertainty, and no calculation should be inferred from the enrollment count alone.

What can a single-group design establish?

In general, a single-group study can report outcomes observed among people who receive the intervention. It does not, by itself, provide a concurrent counterfactual: what would have happened to comparable participants under another treatment or no study treatment. Without a control group, differences between an observed outcome and an external expectation can be affected by patient selection, disease characteristics, other care, or differences in outcome measurement. These are general limits of the design and do not establish that any particular bias occurred in this trial.

Because there is no like-for-like control group, a between-arm treatment contrast is not available. The study's stated objective is an outcome rate in the treated group, not a randomized comparative effect. Even if a single-group outcome estimate had been reported, it would need to be interpreted descriptively and with attention to uncertainty and the population represented.

How should planning calculations be understood?

In general, sample-size calculations depend on an assumed effect, variability or event pattern, significance level, allocation, and analysis method. Such calculations are planning tools, not outcomes observed in a trial. The assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they describe a hypothetical two-arm illustration, not the single-group design recorded for this study. The time-to-event illustrations refer to total events, while other illustrations refer to participants per arm. No numerical planning outputs or trial-specific sample-size justification are reported in the registry record.

The record does not report the trial's own sample-size justification or statistical analysis plan. It also does not report any observed effect estimate that could be used to evaluate such a plan. Planning numbers, if displayed elsewhere alongside the record, should not be confused with actual enrollment, completed follow-up, observed events, or statistical power attained. Sample-size planning is prospective; it cannot compensate for unavailable outcome data.

What does no reported analysis imply?

The registry record lists 0 analyses and provides no primary endpoint estimate. This means there is no reported analysis to interpret, not that a specific statistical test returned a null result. No p-value, model specification, adjustment, censoring rule, or confidence interval is listed. It is also not possible to determine whether any prespecified analysis was attempted, whether analysis procedures changed, or whether an interim analysis was planned. Such details are not reported in the registry record.

For a time-to-event endpoint, general analytical choices can include how to handle participants without an observed event by the end of follow-up, how to define assessment times, and whether to estimate survival curves or a fixed-time rate. Each choice can affect the estimate and its uncertainty. The record defines the endpoint and planned imaging assessments but does not describe these analytical details or present the data needed to evaluate them. No additional statistical result can be recovered from the stated design alone.

10. Multiplicity, Missing Data and Analysis Populations

The study lists one primary endpoint, 12-month PFS, and several secondary outcomes: overall survival, overall time to progression, time to untreatable progression, toxicities, and correlations between MRI changes and PFS or overall survival. The registry record lists 0 analyses and reports no estimates or tests for these outcomes.

Multiplicity is a general concern when a study evaluates several outcomes or performs multiple statistical tests. The more tests conducted, the greater the chance that at least one result may appear notable by chance if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity plan, a testing hierarchy, or any adjustment for multiple comparisons. It is therefore not possible to determine how multiplicity would have been addressed, or whether it affected any analysis.

The record does not report missing-data methods, censoring rules, or an analysis population definition beyond the primary outcome description's explanation that 0 was entered as the analyzed count for confidentiality. No participant-level data or outcome summaries are reported. Consequently, there is no basis for assessing the amount or pattern of missing outcome information, how incomplete follow-up was handled, or whether any sensitivity analyses were performed.

The record states that the study was terminated after 1 participant was enrolled and that confidentiality concerns motivated the analyzed count. That context explains why a public outcome summary is absent, but it does not reveal the participant's outcome. The reason for termination, handling of any data, and details of any statistical procedures are not reported in the registry record.

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

The record establishes that the trial was intended to evaluate 12-month PFS after gemcitabine and cisplatin combined with cTACE in adults with advanced ICC. It also establishes that the study was single-group, was terminated, and recorded enrollment of 1 participant. These registry entries describe the study's design and status; they do not establish an efficacy or safety outcome.

No primary PFS estimate is reported, and the registry lists 0 participants analyzed for that outcome. The record explains that this analyzed count was entered to protect confidentiality after enrollment of 1 participant. As a result, the posted data cannot show the participant's progression status, survival, or follow-up at the endpoint. They also cannot establish a favorable or unfavorable PFS rate.

In general, a single-arm study can describe outcomes in its treated group but cannot make a randomized comparison with another treatment. Here, even a descriptive outcome estimate is unavailable. The study's planned enrollment of 25 patients and planned follow-up do not substitute for actual participant outcomes and should not be interpreted as achieved enrollment or completed observation.

The adverse-event summary lists zeros, while its groups record 0 at risk. Given the absence of analyzed participants and the confidentiality explanation, those counts are not evidence that no toxicity occurred. Similarly, the absence of statistical tests or estimates is not a finding of no difference or no effect. It means that the registry record does not provide results with which to evaluate those questions.

Accordingly, the appropriate statistical conclusion is limited: the record documents the intended research question and a terminated study with very limited enrollment, but it does not report data adequate to answer the primary question or characterize the secondary outcomes. No treatment recommendation follows from these registry data.

12. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a clearly stated research question and an answerable evidence base. The study specified a 12-month PFS objective and a radiographic assessment approach, but the registry record reports enrollment of 1 participant and 0 analyzed for the primary endpoint. Without a reported endpoint estimate, uncertainty interval, or event information, the objective cannot be evaluated from the posted outcomes.

It also illustrates the limits of interpretation in an uncontrolled design. A single-group study may describe outcomes among participants who receive a treatment combination, but it does not provide a randomized comparator for estimating a treatment contrast. In this case, the lack of a comparator is compounded by the absence of reported outcome estimates, so even descriptive assessment is unavailable.

The record distinguishes planned recruitment and follow-up from what was recorded. Its brief description gives a planned enrollment and follow-up schedule, while the status is terminated and actual enrollment is 1. Keeping those quantities conceptually separate is essential: a plan is not completed recruitment, an analyzed sample, or observed evidence.

Finally, the confidentiality note is important for reading the zero analyzed count. It indicates that the count was entered to avoid identifying information after one enrollment, rather than presenting a conventional analysis population. The record therefore offers a useful example of why registry status, design, endpoint definition, analyzed count, and outcome estimate must be interpreted together. The statistical information supports transparency about what was intended and what is publicly summarized, but not conclusions about treatment outcomes.

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 important limitation is that the registry record reports no analyzed participants for the primary endpoint and no PFS estimate. It states that the study was terminated after 1 participant was enrolled and that an analyzed count of 0 was entered because of confidentiality concerns. The available record therefore does not permit assessment of the participant's outcome, follow-up, progression status, or survival.

The study was single-group, with no comparator. Even with outcome data, that design would limit causal interpretation because it does not provide a randomized comparison. In this record, the lack of a comparator combines with the absence of outcome estimates, so neither a treatment contrast nor a useful descriptive endpoint summary is available.

The registry record lists 0 analyses and does not report a statistical analysis plan, sample-size justification, interim-analysis plan, confidence intervals, event counts, or methods for missing data and censoring. The brief description gives planned enrollment and follow-up, but actual enrollment was 1 and the study status is terminated. The reason for termination is not reported in the registry record.

Secondary outcomes are listed, but their estimates are not reported. The adverse-event counts cannot establish safety because the record lists 0 participants at risk and provides no analyzed safety population. The confidentiality explanation also restricts what can be inferred from the posted counts. These limitations are specific to the sparse registry outcome record; they do not identify the participant's clinical course or explain the circumstances of termination.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma — NCT02994251.
• Registry record last updated 2019-12-30; status last verified 2019-12.
• Results first posted 2019-12-30.
• 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.

17. Record Summary

The registry record describes a Phase II, single-center, single-group study sponsored by Yale University. It evaluated gemcitabine and cisplatin with conventional TACE using doxorubicin or mitomycin-C in adults with advanced, unresectable ICC. The primary objective was the 12-month PFS rate, assessed using mRECIST and qEASL with MRI.

The study is listed as terminated, with enrollment of 1. The record lists 0 participants analyzed for the primary endpoint and 0 analyses. Its endpoint description explains that the analyzed count was entered as 0 to protect confidentiality after the single enrollment. No PFS estimate, secondary outcome estimates, or interpretable safety analysis is reported. The planned enrollment and follow-up in the brief description are not completed outcome data. The registry record therefore documents the research question and design but does not answer the primary statistical question.