Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics (NCT04315233), a non-randomized phase 1 study. The primary outcome is Rate of Dose Limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

NCT04315233 was a phase I, open-label, nonrandomized, single-group study sponsored by the University of Utah. The registry lists 12 participants enrolled and describes two planned components: dose escalation followed by dose expansion. In escalation, ribociclib and belinostat were to be given at increasing dose levels and on multiple schedules. The maximum tolerated dose identified during escalation was intended to inform the dose and schedule for expansion; expansion was to use the recommended phase 2 dose.

Dose escalation was open to patients with metastatic triple-negative breast cancer or recurrent ovarian cancer. The planned expansion cohort was limited to triple-negative breast cancer. The primary completion date was 2024-03-14, and the registry status is terminated. The reason for termination is not reported in the registry record.

The posted enrollment is distributed across Cohort 1 Dose Level 0, Dose Level 1A, and Dose Level 1B, with 3, 6, and 3 participants at risk for adverse events in those groups, respectively. No participants were enrolled in Dose Level 2 or Cohort 2. These dose-level groups are not randomized comparisons: participants were not assigned to a concurrent control condition, and the record does not describe a design for causal comparisons between dose levels.

The registry record does not report the planned sample-size justification, a detailed statistical analysis plan, or the rationale for the number of participants enrolled. It also does not report the specific dose amounts or schedules used. The study’s phase and dose-escalation structure identify its stated focus as dose assessment, but they do not establish what dose was selected or what the observed primary endpoint result was.

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: No participants were enrolled in Cohort 1: Dose Level 2 or Cohort 2.

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: No participants were enrolled in Cohort 1: Dose Level 2 or Cohort 2.

6. Primary Endpoint

The registry lists the primary outcome as Rate of Dose Limiting Toxicity (DLT), measured over up to 28 days after initiation of study treatment.

The primary endpoint is the count of participants who experienced a dose-limiting toxicity during the DLT period. The record defines that period as the first treatment cycle, from cycle one day one dosing to cycle two day 1, and gives the timeframe as up to 28 days after initiation of study treatment. Adverse events during this period were to be assessed according to CTCAE v5.0. The endpoint includes specified hematologic and non-hematologic events when attributed as possibly, probably, or definitely related to one or more agents in the combination.

The listed criteria include clinically significant bleeding with Grade 3 thrombocytopenia; Grade 4-5 thrombocytopenia; Grade ≥ 3 febrile neutropenia; Grade 4-5 neutropenia lasting >7 days; any Grade ≥ 4 toxicity; certain Grade 3 toxicities lasting >48 hours despite maximal medical therapy; and Grade ≥ 3 QTcF prolongation. The record excludes clinically non-significant laboratory abnormalities from the stated Grade 3 toxicity criterion.

Generally, a DLT endpoint is used in early-phase dose assessment to identify unacceptable toxicity under a protocol’s defined observation window and rules. The registry record does not report the number of participants meeting these criteria. It therefore does not establish the observed DLT rate or the dose selected from the escalation process.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In a single-group trial, participants receive the study intervention without a separate concurrent control group. In a nonrandomized dose-escalation study, the successive dose levels are part of the planned process for assessing doses; they are not equivalent to randomized treatment arms. Consequently, descriptive counts across the levels do not by themselves estimate what would have happened to comparable participants under another treatment or no study treatment. This is a general statistical point about design, not a reported analysis from this trial.

What does a DLT count describe?

A participant count records how many people met the endpoint definition during the specified observation window. The registry defines both the DLT period and criteria for events to qualify, including severity, duration for some events, and attribution to one or more study agents. Such definitions matter because changing the event criteria or observation window can change what is counted. The posted record defines the endpoint but does not report its observed count, so no trial-specific DLT proportion or uncertainty interval can be stated.

Generally, a confidence interval describes the range of values reasonably compatible with the data under a statistical model and procedure. For a count or proportion, uncertainty is often substantial when the number of participants is small. The registry record does not report a confidence interval or a method for estimating one for the primary endpoint. No interval should be inferred from the enrollment totals alone.

Why does the design limit comparisons?

A randomized comparison is designed to make groups comparable, on average, through random allocation. This trial is explicitly nonrandomized and has no separate control group. Participants at different dose levels may differ for reasons other than dose, and the registry does not report an adjusted analysis addressing such differences. Therefore, contrasts between dose-level counts are descriptive rather than controlled estimates of a dose effect.

General statistical methods can also account for over-dispersion, which occurs when the observed variability in count data exceeds what a simple model assumes. This matters because an overly restrictive model can give uncertainty estimates that are too narrow. The registry record does not report a count model, an assessment of over-dispersion, or an inferential analysis of the safety counts. It would not be appropriate to attribute any such method to the study.

What do the sample-size illustrations mean?

The planning illustrations are not the trial’s reported design justification. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations give a total number of events; for other outcomes, they give participants per arm. These are planning assumptions, not observed trial results and not evidence of observed power.

In general, power is a design-stage probability of detecting a specified effect under stated assumptions. It is not a measure of how likely a result is true after data have been observed. A planning calculation based on an observed effect is especially distinct from the study’s original enrollment plan. The record does not report the trial’s own sample-size justification, and the planning illustrations’ equal-allocation, two-arm framework does not describe this single-group, nonrandomized dose-escalation design. No illustration values are repeated as trial findings.

What analyses are available?

The registry lists four outcome measures and zero analyses. It identifies the primary DLT endpoint and secondary outcomes, but does not report a statistical analysis plan, effect estimates, confidence intervals, or hypothesis tests. The record also does not report the handling of missing observations, the analysis populations, or whether any interim analyses were planned or conducted. Without these details and endpoint results, statistical precision and the robustness of any outcome estimate cannot be assessed.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1: Dose Level 0", "Cohort 1: Dose Level 1A", "Cohort 1: Dose Level 1B")
n      <- c(3, 6, 3)
events <- c(0, 1, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1: Dose Level 0  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 1: Dose Level 1A  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Cohort 1: Dose Level 1B  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary DLT outcome and secondary outcomes for attributed adverse events and serious adverse events, progression-free survival, and objective response rate. It does not report a multiplicity strategy, such as whether any secondary outcomes were designated as confirmatory or how multiple statistical tests would be handled. Since the record lists zero analyses and no outcome results, it is not possible to assess how multiplicity affected any reported inference.

Missing-data methods and the extent of missing outcome data are not reported in the registry record. The record also does not define analysis populations, such as which participants would be included in each endpoint analysis or how participants without a full DLT observation period would be handled. The fact that enrollment is reported does not show that every participant had complete follow-up for every outcome.

General statistical practice distinguishes the enrolled population, the population eligible for a particular endpoint, and the observations actually analyzed. These distinctions matter because exclusions or incomplete follow-up can affect both the estimate and its precision. They cannot be reconstructed from the available record. The endpoint description gives the intended DLT observation window and criteria, but not completeness of observation or participant-level endpoint status.

The reason for trial termination, any interim monitoring rules, and any prespecified statistical decision thresholds are not reported in the registry record. These omissions limit assessment of how the study’s planned analyses were executed and whether the posted outcome information is complete. They do not, by themselves, establish that particular methods were or were not used.

12. 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: disease progression (66.7%), atrial fibrillation (33.3%), dyspnea (33.3%), enterocolitis infectious (33.3%), fever (33.3%).

The adverse-event record gives serious adverse event counts by dose-level group. The listed counts are 3 of 3 participants at Dose Level 0, 6 of 6 at Dose Level 1A, and 2 of 3 at Dose Level 1B. For other adverse events, the counts are 3 of 3, 6 of 6, and 3 of 3, respectively. There were no participants listed at risk in Dose Level 2 or the expansion cohort.

The record lists disease progression as a serious adverse event term at 66.7%, and atrial fibrillation, dyspnea, infectious enterocolitis, fever, and non-cardiac chest pain at 33.3% each. These are the listed percentages for the top serious terms; the record does not provide the underlying term counts in the displayed information. A participant may experience more than one event, so event terms should not be assumed to be mutually exclusive or added together.

Deaths are listed as 3 at Dose Level 0, 5 at Dose Level 1A, and 2 at Dose Level 1B. The record does not establish that these deaths were attributed to treatment. Serious adverse event counts, event-term percentages, and deaths should therefore be read as separate descriptive safety information, not as a causal assessment.

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

The registry record establishes that NCT04315233 was a phase I, open-label, nonrandomized study of ribociclib and belinostat, with a planned dose-escalation phase and a planned expansion cohort. It reports 12 participants enrolled overall, adverse-event counts for three dose levels, and no participants in Dose Level 2 or the expansion cohort. It also specifies a first-cycle DLT endpoint and its event criteria.

These registry entries do not establish the primary endpoint result. The DLT count is not reported in the registry record, and neither a maximum tolerated dose nor a recommended phase 2 dose is reported. Numerical results for progression-free survival and objective response rate are also not reported. The study’s design and endpoint definition are not substitutes for those results.

The safety counts are descriptive. Because participants were not randomized to a control group, and because the record does not report adjusted comparisons, differences among dose levels cannot be treated as causal effects of dose. The death counts do not identify cause or treatment attribution. Likewise, the listed serious-event terms do not establish whether an event was related to the combination.

Generally, early-phase dose assessment addresses the tolerability of a regimen under specified monitoring and endpoint rules; it is not, by itself, a controlled test of clinical benefit. This general distinction does not imply that the intervention was beneficial or harmful. Based on the registry record, conclusions about the combination’s efficacy, comparative safety, or an optimal dose are not supported by reported outcome analyses.

14. Why This Trial Matters Statistically

Statistically, the trial illustrates how a clearly specified endpoint can coexist with an incomplete results record. The DLT definition identifies the observation period, toxicity criteria, and attribution threshold, which are necessary for consistent endpoint classification. Yet the registry record does not report the number of participants meeting that definition. A detailed endpoint description alone cannot quantify the observed safety outcome.

The design also makes the distinction between dose assessment and treatment comparison important. Dose escalation can organize early-phase evaluation across dose levels, but this nonrandomized single-group study does not provide a randomized control contrast. Descriptive counts may help characterize what was recorded in each enrolled group, while remaining insufficient to isolate a dose effect or compare treatment with an alternative.

The record’s enrollment pattern is relevant to precision and scope: participants are reported in three dose-level groups, while Dose Level 2 and the planned expansion cohort have no enrollment. No numerical primary endpoint analysis is available, and the record lists zero analyses. The missing analysis results prevent readers from assessing uncertainty, interpreting the intended dose-selection outcome, or reviewing the listed secondary outcomes as estimates.

Finally, the record makes clear that planning illustrations should not be mistaken for the trial’s own design or its observed power. Their stated equal-allocation, two-arm assumptions differ from the trial’s nonrandomized, single-group structure. Separating design, descriptive safety information, and unreported analyses is essential for a statistically accurate reading of this study.

15. 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.

Several trial-specific limitations restrict interpretation of the registry record. The study is nonrandomized, open-label, and single-group, with no control arm. Dose-level groups therefore do not provide a like-for-like comparison, and the record reports no adjusted analysis that could address group differences. The posted counts are descriptive rather than controlled estimates.

The primary endpoint result is not reported, despite a detailed DLT definition and timeframe. The record also does not report a selected maximum tolerated dose or recommended phase 2 dose. No participants were enrolled in Dose Level 2 or the expansion cohort, limiting what can be learned from those planned components. The reason for termination is not reported in the registry record.

The record lists deaths and serious adverse event terms but does not provide a causal assessment linking deaths or specific events to study treatment. It does not report numerical results for progression-free survival or objective response rate. The absence of a reported statistical analysis plan, analysis populations, missing-data methods, interim-analysis details, and multiplicity strategy further limits assessment of how outcomes were analyzed.

The record gives overall enrollment and group-specific adverse-event counts, but not participant-level data or uncertainty estimates for the primary outcome. Consequently, the precision of any primary safety estimate cannot be assessed. These limits concern what can be concluded from the registry record; they do not establish that unreported analyses or procedures were absent from the conduct of the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics — NCT04315233.
• Registry record last updated 2026-09-04; status last verified 2026-05.
• Results first posted 2026-09-04.
• 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.

19. Record Summary

NCT04315233 was a University of Utah phase I, open-label, nonrandomized, single-group study of ribociclib plus belinostat in metastatic triple-negative breast cancer and recurrent ovarian cancer. It planned dose escalation followed by an expansion cohort restricted to triple-negative breast cancer. The registry reports 12 participants enrolled and a terminated status. The primary endpoint was the participant count with DLT during the first-cycle period, up to 28 days after treatment initiation.

Adverse-event counts are posted for Dose Levels 0, 1A, and 1B; no participants were enrolled in Dose Level 2 or the expansion cohort. The primary endpoint result, selected dose, statistical analyses, and numerical results for the listed secondary outcomes are not reported in the registry record. The posted information supports a descriptive account of the design and selected safety counts, but not a comparative efficacy or causal safety conclusion.