Phase I/II Study of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I/II Study of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma (NCT01406574), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs).

2. Clinical Question

The study’s stated purpose differs by phase: the Phase I step was intended to evaluate safety and determine a recommended dose, while the Phase II step was intended to evaluate efficacy. The primary outcome is a count of participants who experienced dose-limiting toxicities, not a comparative measure of tumor response. Best Overall Response is listed as a secondary outcome, but its results are not reported in the registry record.

The recommended dose was defined in the record as the highest dose at which dose-limiting toxicity occurred at an incidence of < 30%. That definition identifies a dose-selection rule, but does not itself show whether any dose met the rule. The registry lists an enrollment of 23, but the primary endpoint results needed to interpret the rule are not reported. Because allocation was non-randomized and the record identifies no control arm, the study is not a randomized comparison of OPB-31121 against another treatment or against no treatment.

3. Trial Design

This is a Phase I/II, multicenter, open-label, non-randomized study of OPB-31121 in patients with progressive hepatocellular carcinoma. The record gives a planned enrollment of 23 and marks the study as completed. The recorded start is 2011-07, and primary completion is recorded as 2014-03. These registry dates describe the study record; they do not supply additional outcome information.

The official title describes a dose-escalation, therapeutic exploratory trial. The study purpose distinguishes a Phase I step, focused on safety and determination of a recommended dose, from a Phase II step, focused on efficacy. The intervention listings name OPB-31121 and OPB-31121 phase2, while the arm descriptions identify a Phase1 step and a Phase2 step. Four dose groups are listed: OPB-31121 at 50 mg/Day, 100 mg/Day, 200 mg/Day, and 400 mg/Day. The registry record does not report further details about how participants moved between steps or doses.

The study was open-label, with no masking, and allocation is recorded as non-randomized. Consequently, the listed dose groups should not be treated as randomized arms or as balanced comparison groups. Differences between groups could reflect factors other than dose, and the record does not report an adjustment strategy that would address such differences. Although the registry classifies the model as factorial, the study description emphasizes dose escalation and the record does not explain how the factorial classification relates to the conduct of the trial.

The study started in 2011-07 and reached primary completion in 2014-03. Its status is completed. Completion status does not mean that all outcome results or analyses are available in the registry record. In particular, the primary endpoint is named and defined, but its participant counts and any statistical analysis are not reported. A statistical plan, interim analysis details, and sample-size justification are also 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population No statistical analysis provided for Subjects With Treatment Emergent Adverse Events.

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 Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs), measured over From first study medication to on Day 32 (after repeated 28 days medication from Day 4 to 32).

The primary endpoint is the number of participants who experienced dose-limiting toxicities (DLTs). It is a count of participants meeting the DLT definition during a specified observation period, rather than a measure of the severity or frequency of every adverse event. The timeframe runs from the first study medication through Day 32, after repeated 28 days medication from Day 4 to 32. The primary endpoint population is described as DLT-evaluated subjects who achieved at least 75% study drug compliance during a 4-week (28-day) treatment period starting from Day 4.

The DLT definition includes selected blood-count abnormalities, gastrointestinal events despite supportive medication, other severe adverse events, and events requiring interruption of study medication for specified durations or on repeated occasions. The definition therefore sets operational criteria for classifying a participant as having a DLT. It is those criteria, rather than all adverse events, that govern the primary endpoint count.

Such an endpoint is used in dose-escalation research to characterize tolerability over a defined treatment period and inform dose selection. In this record, the recommended dose is defined as the highest dose with DLT incidence < 30%. The registry does not report the number of participants meeting the endpoint at each dose, nor does it report the resulting recommended dose. It explicitly states that no statistical analysis was provided for subjects with DLTs. The endpoint’s definition and rationale can therefore be described, but its observed result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes an open-label, non-randomized Phase I/II study. The primary endpoint is a participant count, and no statistical analysis is reported for that endpoint. The concepts below explain how such data are generally interpreted; they do not describe an analysis reported for this trial.

What does a participant count represent?

For a binary endpoint such as whether a participant experienced a DLT, each evaluated participant is classified according to whether the event occurred under the stated definition and observation period. A count records how many participants meet that definition. To interpret the count as an incidence, the relevant denominator must also be known: the number of participants assessed for that endpoint in the corresponding group. Here, the record identifies an endpoint population based on DLT evaluation and study-drug compliance, but does not report the DLT counts. No incidence by dose can therefore be recovered from the posted primary endpoint information.

Counts also depend on the endpoint rules. The DLT definition applies to selected toxicities and specifies a timeframe ending on Day 32. It includes criteria for blood-count changes, gastrointestinal events despite supportive medications, other severe adverse events, and medication interruptions. Events that do not satisfy those criteria would not necessarily count as DLTs. This distinction matters because a broad adverse-event listing and a protocol-defined dose-limiting toxicity endpoint do not have the same meaning.

Why does the dose-escalation context matter?

In general, early dose-escalation studies use observed toxicity information to guide dose selection. The registry’s stated rule defines the recommended dose as the highest dose at which DLT incidence is < 30%. To apply that rule, the DLT incidence at each relevant dose must be available and based on the endpoint population defined by the study. The record does not report those values, so it is not possible to determine whether the rule selected a dose. This is a descriptive limitation, not a reason to infer that the rule was or was not followed.

The allocation is non-randomized. In general, randomization helps make treatment groups comparable with respect to both measured and unmeasured characteristics. Without randomization, dose groups may differ in participant characteristics or in other ways that affect outcomes. A comparison across dose groups would therefore be descriptive unless supported by an appropriate design and analysis. The registry explicitly cautions that the arms are not a like-for-like control comparison. No statistical adjustment plan is reported in the registry record.

What can a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity, such as an event rate. It helps readers distinguish a relatively precise estimate from one that remains uncertain. For a participant-level binary outcome, the uncertainty depends in part on the number of participants assessed and the number meeting the endpoint. Since the DLT counts are not reported, there is no primary endpoint estimate or confidence interval to interpret. The record also does not report a statistical analysis for subjects with DLTs.

A confidence interval would not by itself correct for the non-randomized design, replace missing outcome reporting, or establish causation. It describes sampling uncertainty under the assumptions of the method used. Whether a statistical method accounts for the study design, endpoint definition, and analyzed population must also be considered. Those analysis details are not reported for the primary endpoint.

How should planning calculations be understood?

In general, sample-size calculations are planning exercises that examine how many participants per arm might be needed under stated assumptions. They are not observed trial outcomes and are not a measure of the study’s achieved statistical power. The sample-size assumptions associated with this record describe an illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a planning calculation, not the non-randomized dose-escalation design itself.

The record does not report a sample-size justification for the trial, nor does it report the statistical plan needed to connect a planning illustration to a particular clinical question. Since no primary DLT result or analyzed effect is reported, such planning assumptions should not be read as evidence of precision or power for the actual study. Sample sizes from planning illustrations are not observed power, and they do not supply missing endpoint results.

Why are the listed arms not a conventional treatment comparison?

In general, a randomized comparison estimates the contrast between assigned groups under the trial’s specified analysis. This study is marked non-randomized and includes dose groups rather than a randomized control arm. A difference between dose groups, even if outcome values were available, would not alone show that dose caused the difference. Participant selection, study conduct, and other group differences may contribute. The registry does not report an analysis that adjusts for these concerns. Its classification of the model as factorial is not accompanied by an explanation of the factors or analysis, so that label cannot be used to infer a particular statistical comparison.

The posted record is therefore most informative about the intended purpose, endpoint definition, study design, and listed safety counts. It is not sufficient to reconstruct a primary endpoint analysis. Any stronger statistical interpretation would require outcome counts and analysis details that are not reported in the registry record.

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("OPB-31121: 50 mg/Day", "OPB-31121: 100 mg/Day", "OPB-31121: 200 mg/Day", "OPB-31121: 400 mg/Day")
n      <- c(7, 4, 7, 5)
events <- c(0, 0, 1, 4)
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  OPB-31121: 50 mg/Day  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  OPB-31121: 100 mg/Day  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  OPB-31121: 200 mg/Day  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  OPB-31121: 400 mg/Day  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary endpoint of participants who experienced DLTs and identifies Best Overall Response as a secondary outcome. It does not report a multiplicity strategy, such as how statistical testing across outcomes or dose groups would be handled. The registry record also does not report a statistical analysis for subjects with DLTs, and it does not provide the primary endpoint counts. No conclusion about statistical significance or control of false-positive findings is therefore available from this record.

Missing outcome reporting is distinct from missing participant data within an analysis. The registry record does not describe whether participants lacked endpoint assessments, how incomplete observations were handled, or whether any imputation or sensitivity analyses were used. It also does not report the number of participants evaluated for the primary endpoint in each dose group. The endpoint population is defined by DLT evaluation and achievement of at least 75% study drug compliance during a 4-week (28-day) treatment period starting from Day 4, but the record does not state how many participants met that definition.

Analysis populations are also not described beyond that endpoint population definition. The registry does not report whether other populations were used for the Phase II efficacy evaluation or for Best Overall Response. Without these details, readers cannot determine how exclusions, incomplete follow-up, or differences between enrolled and evaluated participants may have affected results. These are reporting gaps; they do not establish that data were missing or that any particular handling method was used.

The record states an enrollment of 23, but this does not supply the endpoint-specific denominators or analysis populations. No total should be inferred for a particular outcome from enrollment alone. The registry record does not report an interim analysis plan or a detailed statistical analysis plan.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gait disturbance (20.0%), jaundice (20.0%), peripheral sensory neuropathy (20.0%).

The safety figures are reported separately for serious adverse events and other adverse events, by dose group. For OPB-31121 at 50 mg/Day, the record lists 0 serious events among 7 at risk and 7 other events among 7 at risk. For 100 mg/Day, it lists 0 serious events among 4 at risk and 4 other events among 4 at risk. For 200 mg/Day, it lists 0 serious events among 7 at risk and 7 other events among 7 at risk. For 400 mg/Day, it lists 2 serious events among 5 at risk and 5 other events among 5 at risk.

These are descriptive counts, not randomized comparisons. The groups were not allocated randomly, and the record cautions that they are not like-for-like control groups. The listed counts do not establish that dose caused any difference. Serious adverse event figures should also not be confused with DLT counts: the primary endpoint uses its own event criteria and timeframe, and its results are not reported. Death counts are not reported in the registry record. The listed serious terms are Gait disturbance, Jaundice, and Peripheral sensory neuropathy, each recorded as 20.0%; the record does not provide further context for interpreting those term percentages.

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

The record establishes that OPB-31121 was studied in a completed, open-label, non-randomized Phase I/II trial in patients with progressive hepatocellular carcinoma. It describes a Phase I safety and dose-selection purpose, a Phase II efficacy purpose, four listed dose groups, and a primary endpoint based on dose-limiting toxicities through Day 32. It also provides selected adverse-event counts by dose group. These features allow a reader to understand the broad clinical and statistical question the study was intended to address.

The record does not establish how many participants experienced DLTs, the incidence at each dose, or which dose met the stated recommended-dose criterion. It does not report the primary endpoint analysis. Best Overall Response is listed as a secondary outcome, but its results are not reported in the registry record. The available information therefore does not permit an interpretation of the study’s efficacy findings or a quantitative conclusion about its primary safety endpoint.

Nor does the record support a causal comparison among dose groups. Allocation was non-randomized, there was no masking, and the registry cautions that the arms are not a like-for-like control comparison. The serious adverse event counts are descriptive, and they should not be read as estimates of a randomized dose effect. The DLT endpoint and the broader serious adverse event listings are also different measures.

These limits concern what can be concluded from the registry record. They do not show that the study had no results, that no analysis was conducted elsewhere, or that no events occurred. The record’s completed status does not resolve its missing outcome reporting. A sound interpretation keeps the design, endpoint definition, available safety counts, and unreported primary results separate.

14. Why This Trial Matters Statistically

This trial illustrates a common statistical challenge in early-phase clinical research: the most important question may depend on a clearly defined event count, but that count is not always available in the registry record. Here, the study identifies DLTs as the primary endpoint and supplies operational criteria and a dose-selection rule. Those definitions make clear what the intended evidence should address, yet the absence of the actual counts prevents readers from assessing the rule’s application.

The record also demonstrates why design labels matter. A dose-escalation study with non-randomized groups serves a different inferential purpose from a randomized treatment comparison. The listed dose groups can describe where participants received treatment, but they do not automatically provide unbiased estimates of differences between doses. The registry’s caution that the arms are not like-for-like controls is important context for interpreting any descriptive safety figures.

Another statistical lesson is that endpoint definitions and broader safety summaries should not be conflated. A DLT is defined using specified events, timing, and criteria, while serious adverse event listings are a separate form of safety information. Reporting one does not replace the other. Keeping the measures distinct helps avoid attributing a result to an endpoint it does not represent.

Finally, completion status, enrollment information, and detailed outcome reporting are different pieces of evidence. A completed record with a named primary endpoint does not necessarily contain the results needed to evaluate that endpoint. Transparent reporting of analyzed populations, outcome counts, and analysis methods is essential for readers to judge both the size and uncertainty of findings. This record makes the intended clinical question visible while leaving the central primary endpoint result unavailable.

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.

The primary limitation for interpretation is that DLT counts and any statistical analysis of those counts are not reported in the registry record. The recommended dose cannot be identified from the information reported, despite the stated dose-selection criterion. The endpoint population is described, but endpoint-specific denominators are not reported. This prevents estimation of the primary endpoint incidence from the registry information.

The non-randomized, open-label design further limits comparisons across dose groups. The registry itself cautions that the arms are not like-for-like control comparisons. The record does not describe an adjustment plan that would address differences between groups. Its factorial model label is not explained in enough detail to clarify how it relates to the dose-escalation description or to any analysis.

Outcome reporting is incomplete for interpretation of the study’s stated Phase II purpose as well. Best Overall Response is listed as a secondary outcome, but results are not reported in the registry information. The record also does not report a detailed statistical plan, sample-size justification, handling of incomplete outcome data, or analysis populations beyond the DLT population definition. Interim analyses are not reported in the registry record.

The listed serious adverse event counts are descriptive and do not resolve these gaps. Death counts are not reported, and the serious-event term percentages lack further context in the record. These limitations restrict conclusions that can be drawn from the registry record; they do not establish what may have been reported elsewhere or whether additional analyses were performed outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase I/II Study of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma — NCT01406574.
• Registry record last updated 2015-06-08; status last verified 2015-05.
• Results first posted 2015-06-08.
• 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

This completed Phase I/II study evaluated OPB-31121 in patients with progressive hepatocellular carcinoma. It was multicenter, open-label, and non-randomized, with a dose-escalation Phase I purpose focused on safety and recommended-dose determination and a Phase II purpose focused on efficacy. The registry lists dose groups of 50 mg/Day, 100 mg/Day, 200 mg/Day, and 400 mg/Day.

The primary endpoint was the number of participants with DLTs through Day 32, under a defined event and compliance framework. The record does not report DLT counts or a statistical analysis for that endpoint. Best Overall Response is listed as a secondary outcome, but its results are not reported. Descriptive serious and other adverse event counts are available by dose group, but the registry cautions that the non-randomized groups are not like-for-like controls. Thus, the record supports description of the design and endpoint definition, but not conclusions about the primary endpoint result or efficacy.