Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC) (NCT03875859), a na phase 2 study. The primary outcome is Overall Response (OR).

2. Clinical Question

This is a question about lesion response in a small, single-group study, not a comparative estimate of treatment effect. The registered primary outcome is called Overall Response (OR), and it is expressed as a number of tumor lesions. In this record, OR means lesions meeting the complete-response or partial-response definition; it is not an odds ratio.

The stated purpose was to determine whether 8 weeks of topical treatment applied three times daily would suppress SCC. The primary outcome timeframe is 10 weeks, which is the interval within which a qualifying response could be counted. The record does not report how response was observed over that interval, when assessments occurred, or how the assessment was conducted. Those details are not reported in the registry record.

The question therefore needs to be read narrowly: it concerns recorded responses among treated lesions in the enrolled study, without a concurrent comparison group. The registry lists an enrollment of 4, but it does not give the number of eligible and treated lesions or the primary outcome value. The planned clinical question is identifiable; its answer cannot be established from the outcome information recorded.

3. Trial Design

NCT03875859 is registered as a phase 2, open-label, single-group trial of topical remetinostat gel as neoadjuvant therapy in people undergoing surgical resection of SCC. Kavita Sarin is listed as sponsor. The record lists the study start as 2019-12-12 and primary completion as 2020-05-14. Its current status is terminated. The reason for termination is not reported in the registry record.

The intervention was remetinostat gel 1%, applied to at least 1 SCC three times daily. The brief summary describes an intended treatment period of 8 weeks. Because the study is single group and allocation is not applicable, the design does not include a separate randomized comparison arm. Masking is listed as none, so the trial is open label. The record does not report further operational details about treatment delivery, adherence, or surgical timing.

Enrollment is listed as 4. That figure describes the registered study enrollment, not the number of lesions assessed for the primary outcome. The primary outcome population is defined as all treated lesions for all participants, but the registry record does not state how many lesions were eligible, treated, or included. It also does not give a participant flow account that would explain any differences between enrollment and analysis populations.

The primary outcome is Overall Response, measured as a count of tumor lesions with complete or partial response any time within 10 weeks. The registry also lists secondary outcomes concerning adverse events contributing to treatment discontinuation or interruption and the number of participants who discontinued or had an interruption. It lists 3 outcome measures, but the record does not provide a full set of numerical results for them. It reports 0 analyses.

A single-group design can describe what happened among participants or lesions receiving the intervention, but it cannot separate treatment-associated changes from other explanations using a concurrent randomized comparison. The record does not report a protocol rationale for the design, a sample-size justification, or additional design details. These matters are not reported in the registry record.

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: All treated lesions for all participants were included in the analysis.

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.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response (OR), measured over 10 weeks.

The primary endpoint is Overall Response (OR), measured in tumor lesions over a timeframe of 10 weeks. The registry defines a complete response as disappearance of a target lesion. It defines a partial response as at least 30% decrease in the sum of the longest diameter of the target lesion. Overall Response is the count of lesions meeting either the complete-response or partial-response definition among all eligible and treated lesions, at any time within the timeframe.

This endpoint is used to describe whether treated lesions meet the registered response criteria during the stated assessment window. It is a lesion count, not a proportion, rate, or time-to-event measure in the definition recorded. No primary endpoint value is reported in the registry record, so the observed number of lesions meeting these criteria cannot be stated.

In general, a response endpoint can provide a structured way to classify changes in a target lesion using prespecified criteria. A count is descriptive of the number of qualifying lesions, but interpretation also depends on the size and definition of the population in which the count is observed. Here, the record says all treated lesions for all participants were included, but does not report the number of those lesions, the number of participants contributing lesions, or the count with complete or partial response.

The registry’s description does not report whether response assessments were independently reviewed, how measurements were obtained, how missing or unevaluable lesions were handled, or whether multiple lesions from one participant were analyzed in a way that accounts for their relationship. Those details are not reported in the registry record. Without them and without an outcome value, the endpoint can be described, but its observed result and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the design, outcome definition, analysis population, and reported uncertainty. For this trial, the registry identifies a single group and a lesion-count response endpoint. It does not report a primary outcome value, confidence interval, hypothesis test, or other statistical analysis result. As a result, the statistical discussion must distinguish the registered plan and definitions from results that are not recorded.

What a single-group design can estimate

In general, a single-group study can describe outcomes observed in the group receiving the intervention. If a response count and a clearly defined denominator are reported, those quantities can characterize observed responses in that study population. Without a concurrent control group, however, the design does not directly estimate how outcomes differ from what would have happened under another treatment or under a control condition. Changes may have explanations other than the intervention, and the design does not isolate those explanations through random allocation.

This distinction matters for the present endpoint. The registry defines a count of lesions meeting response criteria, but does not report the count or the number of eligible and treated lesions. Without both, the magnitude of observed response cannot be described. No difference between groups can be estimated because the registry records no comparison group.

How to interpret a lesion count

The endpoint is a number of tumor lesions, not a participant-level response proportion. The registry states that all treated lesions for all participants were included. In general, the interpretation of a count depends on how many observations could contribute to it and how those observations relate to one another. Multiple lesions from the same participant may share biological or measurement characteristics. If so, they may not provide as much independent information as the same number of lesions distributed across different participants.

General statistical methods for clustered observations account for such relationships when estimating uncertainty. The registry record does not report whether any such method was used. It also does not report the number of lesions, how eligible and treated lesions were identified, or whether all observations could be evaluated. The count alone, even if it were available, would not supply all the information needed to judge precision.

Precision and uncertainty

In general, a confidence interval describes a range of values reasonably compatible with the data under the model and method used. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies within that particular interval. A narrower interval indicates greater precision under the chosen method, while a wider interval indicates less precision. The registry record does not report a confidence interval for the primary endpoint, and no interval can be described from the registered details.

In general, a p-value addresses how compatible data are with a specified null hypothesis under a statistical model. It does not measure the size or clinical importance of an effect, nor does it establish causation. No p-value or hypothesis test for the primary endpoint is reported in the registry record. Because the endpoint result is also absent, there is no basis for discussing statistical significance or estimating the magnitude of response.

Planning illustrations and observed results

The record includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are described as based on the observed effect, with the effect to detect expressed as a stated fraction of that observed effect. They are not the trial’s own design or a sample-size justification. For time-to-event settings, the stated convention is total events using the Schoenfeld method; for other settings, the convention is participants per arm.

Those planning assumptions do not turn this single-group trial into a two-arm comparison. They are not observed power and should not be read as a property of the trial’s evidence. The registry record does not report the observed primary response value needed to judge the relationship between that endpoint and any planning illustration. The planning assumptions also do not establish that the trial was designed or conducted using those assumptions.

Over-dispersion and model choice

In general, count outcomes can vary more widely than a simple statistical model assumes. This is called over-dispersion. If present, it can make standard errors too small when the model underestimates variability, leading to intervals that are too narrow and tests that appear more decisive than warranted. A count outcome can also require a model that reflects its data structure, including whether observations are clustered or whether many observations have no events. These are general considerations, not claims about the data in this trial.

The registry record does not report a model for the lesion count, a dispersion assessment, or a method for accounting for lesions within participants. Since no outcome count or analysis is recorded, there is no basis to determine whether over-dispersion occurred or which model would have been appropriate. The endpoint definition identifies what was to be counted, but does not specify the statistical procedure used to analyze it.

What the analysis record supports

The record lists 3 outcome measures and 0 analyses. It names secondary outcomes concerning adverse events contributing to treatment discontinuation or interruption and participants who discontinued treatment or had treatment interruption. Numerical results for those secondary outcomes are not reported in the registry record. The serious and other adverse event counts are separately listed, but they do not substitute for a primary response analysis.

Overall, the registry supports a description of the study design, intervention, endpoint definition, status, and selected safety counts. It does not support an estimate of response, a measure of uncertainty around response, a treatment comparison, or an assessment of a statistical test. Those conclusions require results and methods that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies Overall Response as the primary outcome and lists 3 outcome measures. It also names secondary outcomes concerning adverse events contributing to treatment discontinuation or interruption and the number of participants who discontinued or had an interruption. The record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan for controlling the chance of false-positive findings across multiple tests. Those details are not reported in the registry record.

In general, multiplicity arises when multiple outcomes, comparisons, timepoints, or subgroups are tested. The more tests that are considered, the greater the chance that at least one result may appear unusual by chance, depending on the testing approach. A prespecified hierarchy or adjustment can help address that issue. Because the record reports 0 analyses and no outcome test results, there is no basis to determine whether multiplicity affected any inference.

The registry describes the primary analysis population as all treated lesions for all participants. It does not report how missing, unevaluable, or otherwise excluded lesions were handled. It also does not report participant-level analysis populations such as intention-to-treat or per-protocol groups. The difference between enrollment and the number contributing to the primary endpoint is not described, and the record does not state whether any participants or lesions lacked outcome assessment.

In general, missing-data handling can affect an estimate when the chance that an observation is missing is related to its outcome or other characteristics. Clear reporting of the amount, reasons, and handling of missing observations helps readers judge this possibility. Those details are not reported in the registry record. No assumptions for missing responses, imputation method, or sensitivity analysis are recorded.

The trial is listed as terminated, but the reason is not reported. The record does not state whether termination affected the availability or completeness of outcome data. Therefore, neither the termination status nor the absence of a result should be treated as evidence about the direction of the response outcome.

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 non-serious adverse event terms

The registry reports serious adverse event counts for the remetinostat group: 4 participants were at risk, 0 were affected, and deaths were 0. The listed count for other adverse events is 4 affected among 4 at risk. These are distinct categories in the record; the 0 serious adverse events should not be read as meaning that no adverse events of any kind occurred.

The record lists no serious adverse event terms. It does not provide details about the other adverse events, including their descriptions, severity, timing, duration, or whether they were considered related to remetinostat. The named secondary outcomes concern adverse events contributing to treatment discontinuation or interruption and participants who discontinued or had an interruption, but their numerical results are not reported in the registry record.

In general, adverse event counts describe events recorded during a study and do not by themselves establish cause. Interpretation also depends on definitions, observation time, completeness of reporting, and the number of people monitored. Here, the registry lists 4 at risk for both serious and other adverse event counts, but does not state the observation duration for the safety summary. The small registered enrollment and limited descriptive detail mean these counts should be read as a record of reported events, not as a comprehensive estimate of safety.

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

The registry establishes that NCT03875859 was a phase 2, open-label, single-group trial of topical remetinostat gel 1% for SCC, with enrollment listed as 4 and status terminated. It defines a lesion-level primary response outcome within 10 weeks and describes the intended topical regimen as three times daily for 8 weeks. It also records selected safety counts. These details describe the registered study, but they do not provide a numerical primary response result.

The record does not report how many lesions had complete response, partial response, or either response category. It does not report the total number of eligible and treated lesions, or a statistical estimate of uncertainty around response. Consequently, the posted registry information cannot establish the observed response level or its precision. The absence of a reported outcome is not evidence of no response and is not evidence of response.

The design also limits interpretation. There is no separate comparison group, and the trial is open label. Any outcome description from this study would characterize the treated lesions in this study, rather than estimate a randomized contrast. A single-group observation does not by itself distinguish the contribution of treatment from other possible explanations for an observed change.

The safety record lists 0 serious adverse events among 4 at risk, 0 deaths, and 4 other adverse events among 4 at risk. The record does not provide terms for the serious events or detailed descriptions of the other events. These counts should not be expanded into claims about event types or causation.

In general, a trial record is most informative when it reports outcome values, analysis populations, missing-data handling, and methods for quantifying uncertainty. Those elements are not reported for the primary endpoint. The status is terminated, but the reason and its implications for data collection are not reported. The registry information therefore supports a description of the study and its definitions, while leaving the clinical response result and the reasons for termination unresolved.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is expressed at the lesion level while enrollment is expressed at the participant level. The registry says all treated lesions for all participants were included, but does not report the number of lesions. In general, the distinction matters: multiple lesions from one participant may share characteristics, so the information in a lesion count depends not only on the number counted but also on how observations are distributed across participants and handled analytically.

The design also illustrates the difference between a response description and a comparative treatment effect. A single-group study can record whether lesions meet response criteria, but without a control group it cannot estimate a randomized difference against another condition. The open-label design and absence of masking are additional features relevant to how measurements and classifications are interpreted. The record does not describe a blinded assessment procedure.

Another statistical issue is the difference between a defined endpoint and a reported result. The registry gives explicit response criteria and a timeframe, but it does not report the primary response count, denominator, or uncertainty estimate. A clearly written endpoint is useful for understanding what was meant to be measured; it does not by itself establish what the data showed.

The record’s termination status, along with the absence of a primary outcome result and analysis results, also highlights the importance of complete outcome reporting. The reason for termination and the completeness of outcome collection are not reported. Without those details, readers cannot determine why the study ended or whether the lack of a result reflects incomplete collection, nonreporting, or another circumstance.

These considerations make the record useful for understanding study structure and statistical limits, while underscoring that design details and endpoint definitions cannot replace the actual outcome data. No claim about response effectiveness follows from the record as reported.

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 most direct limitation is that the registry record does not report the primary response count. It defines complete and partial response and gives a 10-week timeframe, but does not state how many lesions met either criterion. The total number of eligible and treated lesions is also not reported, so neither a count nor a proportion can be interpreted from the record.

Enrollment is listed as 4, while the primary population is described in terms of treated lesions. The record does not report participant characteristics, the lesion count, or the number of participants contributing evaluable outcome data. It also does not report how any missing, unevaluable, or excluded lesions were handled. These omissions prevent assessment of the endpoint denominator and analysis population.

The study is single group, open label, and has no randomized control comparison. That design does not support a direct comparison with another treatment or control condition. The registry does not describe blinded response review, lesion measurement procedures, or a statistical approach for observations that may be clustered within participants. Such details are not reported in the registry record.

The record lists 0 analyses and does not report a confidence interval, p-value, or other measure of primary outcome uncertainty. It does not report multiplicity procedures, missing-data methods, a sample-size justification, or interim analyses. These matters are not reported in the registry record, so none should be assumed.

The status is terminated, but the reason is not reported. The record also does not explain whether termination affected outcome collection. Safety reporting is limited to aggregate counts: 0 serious adverse events among 4 at risk, 0 deaths, and 4 other adverse events among 4 at risk. Serious event terms and details of other adverse events are not reported. Together, these limits mean the record supports a description of the registered study but not a complete assessment of its response results or safety profile.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Topical Remetinostat Gel as Neoadjuvant Therapy in Patients With Squamous Cell Carcinoma (SCC) — NCT03875859.
• Registry record last updated 2021-05-20; status last verified 2021-04.
• Results first posted 2021-05-20.
• 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

NCT03875859 is a phase 2, open-label, single-group trial of topical remetinostat gel 1% for SCC. The registry lists enrollment of 4, sponsor Kavita Sarin, study start 2019-12-12, primary completion 2020-05-14, and status terminated. The reason for termination is not reported in the registry record.

The intervention description specifies application to at least 1 SCC three times daily; the brief summary describes an intended 8-week course. The primary endpoint is the number of treated lesions with complete or partial response within 10 weeks. The record defines those response criteria but does not report the observed primary outcome value or a statistical analysis result.

The registry lists secondary outcomes concerning adverse events contributing to treatment discontinuation or interruption and participants who discontinued or had an interruption. It reports 0 serious adverse events among 4 at risk, 0 deaths, and 4 other adverse events among 4 at risk. Further event details, outcome-analysis methods, and the reason for termination are not reported in the registry record.