A Study of BMS-863233 in Patients With Advanced and/or Metastatic Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of BMS-863233 in Patients With Advanced and/or Metastatic Solid Tumors (NCT00886782), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233.

2. Clinical Question

This is a dose-finding and safety question, not a question about comparative effectiveness. The primary outcome counts participants with a DLT during the stated observation window. A DLT was defined as a drug-related adverse event occurring during the first cycle of therapy and assessed using NCI CTCAE v3.0. That definition makes the outcome dependent on both the event and the registry’s attribution and grading criteria.

The study included people with advanced and/or metastatic solid tumors, a broad clinical population rather than a single cancer type. The registry record does not provide further eligibility details in the registry record reported for this trial. It also does not describe a control intervention or a randomized allocation procedure. The listed dose groups allow safety to be described by dose, but without a control group, differences between groups cannot be interpreted as controlled treatment comparisons.

The study’s stated purpose includes determining a maximum tolerated dose. The primary outcome is relevant to that purpose because dose-limiting toxicities are used in dose-finding research to identify tolerability concerns. However, the registry record does not report a numerical primary-outcome result or a maximum tolerated dose determination. The available information therefore identifies the question the study was designed to address, but does not establish its answer.

3. Trial Design

The registry record identifies NCT00886782 as a phase 1/2 study of BMS-863233 in participants with advanced and/or metastatic solid tumors. Its official title describes a multiple ascending dose study evaluating safety, pharmacokinetics, and pharmacodynamics. The record lists Bristol-Myers Squibb as the sponsor and enrollment of 11 participants. The study status is terminated. The recorded start date is 2009-05-31, and the primary completion date is 2010-08-04. The reason for termination is not reported in the registry record.

The design is recorded as single group, with no masking and allocation marked NA. No separate control group is identified. The safety groups shown in the registry record are BMS-863233 25 mg, 50 mg, and 100 mg. The record does not provide a description of how participants were assigned among those dose groups, nor does it give further details of dose administration in the arm descriptions. The title’s reference to multiple ascending doses does not by itself establish the operational rules used to move between doses.

The primary outcome is the number of participants with DLTs of BMS-863233, assessed over up to 28 days. The outcome population is all treated participants. Secondary outcomes include plasma concentration and pharmacokinetic measures—Cmax, Tmax, AUC(TAU), clearance, effective elimination half-life, accumulation index, and trough concentration—as well as change from baseline in mean heart rate measured by ECG. The registry record lists 17 outcome measures overall, but numerical results for these measures are not reported in the available record information.

A single-group design can describe events observed during treatment and can support exploratory dose-finding work. It does not provide a concurrent control for separating treatment-associated events from the background effects of advanced cancer, other care, or chance. Dose groups also need not be comparable in their participant characteristics unless assignment and baseline information establish that. Those details 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated participants

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 With Dose Limiting Toxicities (DLTs) of BMS-863233, measured over Up to 28 days.

The primary endpoint counts participants who experienced a dose-limiting toxicity of BMS-863233. Its stated timeframe is up to 28 days, and the outcome population is all treated participants. The registry defines a DLT as an adverse event deemed drug-related and occurring during the first cycle of therapy, using NCI CTCAE v3.0. This is a participant count: it concerns how many people met the DLT definition, rather than the total number of adverse-event episodes.

DLT counts are used in early dose-finding research because tolerability at different doses is central to deciding whether dose levels merit further study. A count can be presented by dose group and can make the observed frequency of the defined event visible. It is not, by itself, a complete account of safety: it reflects the specified event definition and observation period, and it does not capture every possible outcome of treatment.

The endpoint also depends on judgments about whether an adverse event is drug-related and how it is graded under the named criteria. The registry record does not provide further adjudication details, nor does it report the numerical count of participants with DLTs. As a result, the endpoint definition and intended role are described, but the primary safety result cannot be interpreted quantitatively from the registry record.

The study purpose mentions maximum tolerated dose, but the record does not report a maximum tolerated dose determination. A DLT count is relevant evidence for such a determination; it is not interchangeable with the determination itself. Dose-finding decisions ordinarily depend on the prespecified approach to evaluating events across dose groups, and that statistical or operational approach is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a count of participants with DLTs. A count outcome records how many participants satisfy the event definition. For interpretation, the count is usually considered alongside the number of participants observed, the length of follow-up, and the rules for classifying an event. In this study, the record specifies all treated participants as the population and up to 28 days as the timeframe. It defines DLTs by drug relationship, timing during the first cycle, and NCI CTCAE v3.0 assessment.

The registry record does not provide a numerical DLT result or an analysis of that outcome. It does not report an estimated event frequency, an uncertainty interval, or a statistical test. Without such results, the definition alone cannot tell readers how many participants experienced a DLT. The adverse-event counts reported by dose are not a substitute for the primary outcome, because the serious and other adverse-event summaries are not stated to use the DLT definition.

What does an uncertainty interval add?

As a general statistical explanation, an uncertainty interval describes a range of values compatible with the observed data under a specified method. It helps distinguish an estimate from its precision: a point estimate alone does not show how much uncertainty is associated with it. In small groups, uncertainty can be substantial even when the observed count is clear. No uncertainty interval for the primary DLT outcome is reported in the registry record, so its precision cannot be assessed from the stated primary result.

Why does the single-group design matter?

As a general principle, a control group offers a reference for estimating how outcomes differ under alternative conditions. This study is recorded as single group, with no masking and allocation marked NA. It therefore does not provide a randomized control comparison. Descriptions across the dose groups can show the events recorded at each dose, but they do not isolate a causal dose effect. Differences could reflect participant characteristics, disease course, chance, or other factors; the registry record does not report information that would allow those explanations to be separated.

The arm descriptions do not explain dose assignment, and the registry record does not report the method used to select or advance doses. The official title describes multiple ascending doses, but operational dose-escalation rules are not reported. In dose-finding research, those rules matter because the interpretation of observed DLT counts depends on how the next dose was chosen and which participants contributed to each decision. No particular escalation algorithm should be inferred from the title alone.

How should the adverse-event counts be read?

The serious and other adverse-event figures are descriptive counts for the dose groups. A count is not an adjusted comparison, and the registry gives no control arm against which to compare it. The reported counts also do not establish attribution to treatment. The serious-event term percentages identify terms recorded in the registry, but do not provide a controlled estimate of the risk associated with BMS-863233. A percentage may describe a share or frequency according to the registry’s reporting convention; the record information does not provide the underlying term-specific denominators or further calculation details.

Over-dispersion is a general issue in count data. It occurs when observed variability exceeds what a simple count model assumes. If relevant, it can make standard errors too small and uncertainty appear narrower than warranted. The registry record does not report a count model or dispersion estimate for the primary outcome, and the primary endpoint is specifically a participant count rather than a reported total event count. No model choice or adjustment should therefore be attributed to the study.

What can the planning assumptions tell readers?

The study’s stated sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is not the trial’s own design rationale: the registry records a single-group study and no separate control arm. The effect to detect is expressed as a stated fraction of the observed effect. Such planning calculations are hypothetical assessments of sample size under assumptions; they are not observed power and do not show what the trial was capable of concluding after enrollment. The registry record does not report a sample-size justification for the study itself, and no specific planning sample-size result is reported in the record information.

The secondary outcomes cover pharmacokinetics, including concentration, timing, exposure, clearance, elimination, accumulation, and trough concentration, as well as change from baseline in mean heart rate by ECG. These outcomes can characterize how a drug behaves in the body and describe selected measurements over time. Their inclusion does not imply that results were reported. Numerical results and statistical analyses for these measures 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("BMS-863233 25 mg", "BMS-863233 50 mg", "BMS-863233 100 mg")
n      <- c(3, 3, 5)
events <- c(0, 0, 1)
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  BMS-863233 25 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  BMS-863233 50 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  BMS-863233 100 mg  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures, including the primary DLT count, several pharmacokinetic measures, and ECG change from baseline. When a study examines multiple outcomes, the chance of at least one apparently notable result can increase if each is tested separately. As a general statistical principle, investigators may specify which outcome is primary and describe whether and how they will account for multiple comparisons. The record identifies a primary outcome but does not report a multiplicity strategy or a complete statistical analysis plan. It is not possible to determine whether any adjustment was intended or used.

No analyses are listed in the registry record. Numerical results for the primary outcome are not reported, and the record information does not give inferential results for the secondary outcomes. It also does not report interim analyses, stopping rules for toxicity, or the method used to determine the maximum tolerated dose. These omissions prevent assessment of how outcome multiplicity, dose decisions, or any repeated review of accumulating safety data was handled.

The primary analysis population is identified as all treated participants. The registry record does not report how missing outcome data were handled, whether all treated participants had complete follow-up, or how participants who stopped treatment were included in the primary endpoint assessment. These details matter because a participant’s opportunity to experience or report an event can depend on follow-up and treatment exposure. No missing-data method should be assumed.

The registry record also does not report a formal sample-size justification for the study. The planning assumptions described for sample-size illustrations are not evidence of the trial’s original design rationale. Without a reported analysis plan, missing-data approach, and numerical outcome results, the degree to which the findings answer the prespecified primary question cannot be evaluated.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malignant neoplasm progression (40.0%), localised oedema (33.3%), pyrexia (33.3%), bacteraemia (33.3%), musculoskeletal pain (33.3%).

The safety summaries list serious adverse events, other adverse events, and deaths separately for the BMS-863233 dose groups. For 25 mg, 1 of 3 participants at risk was reported with a serious adverse event, and 3 of 3 with other adverse events; deaths were 0. For 50 mg, the corresponding figures were 1 of 3, 2 of 3, and 1 death. For 100 mg, they were 4 of 5, 5 of 5, and 2 deaths. These are descriptive figures for the participants at risk in each group.

The counts should not be read as a comparison against an untreated group: no control group is listed. They also do not establish that the events were caused by the study drug. Serious adverse events and DLTs are not interchangeable categories. The primary DLT definition requires a drug-related event during the first cycle and uses NCI CTCAE v3.0; the registry’s serious-event counts are not reported as DLT counts. The numerical primary DLT result is not reported in the registry record.

The listed serious-event terms include malignant neoplasm progression at 40.0%, and localised oedema, pyrexia, bacteraemia, musculoskeletal pain, and spinal cord compression, each at 33.3%. These percentages should be interpreted according to the registry’s reporting convention; the record does not give further term-specific denominator details. The counts are useful descriptions of recorded events, not estimates of comparative risk or proof of causality.

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

The registry record establishes that this was a phase 1/2, single-group study of BMS-863233 in people with advanced and/or metastatic solid tumors. It states that the study focused on safety, tolerability, and maximum tolerated dose, and defines the primary outcome as the number of participants with DLTs during up to 28 days. It also identifies dose groups and reports selected adverse-event counts. These details describe the research question and some of the safety information recorded.

The record does not report the numerical primary DLT outcome. It therefore does not show how many treated participants met the DLT definition, nor does it report a maximum tolerated dose determination. The named pharmacokinetic and ECG outcomes do not come with numerical findings in the registry information. Consequently, no conclusion about the observed primary outcome or those secondary measurements can be drawn from the record.

The adverse-event counts do not establish that BMS-863233 caused the events. With no separate control group, the study cannot provide a randomized comparison that distinguishes treatment effects from disease progression, background risk, or other influences. Counts across dose groups are descriptive, not evidence of a causal dose-response relationship. The small group sizes also mean that event descriptions may be sensitive to the experience of individual participants; this is a general limitation of interpreting sparse safety data.

The recorded status is terminated, but the reason for termination is not reported in the registry record. Termination should not be treated as a result or as an explanation for the missing numerical outcomes. It does not, by itself, establish harm, lack of benefit, or the reason the study stopped.

In short, the record documents a safety and dose-finding study with a defined DLT endpoint, some descriptive safety information, and several planned pharmacokinetic and ECG outcomes. It does not report the primary numerical result, the analysis needed to quantify its precision, or a comparative treatment effect. The scope of what can be concluded is therefore limited to the design and reported descriptive information, rather than a judgment about clinical benefit or harm.

14. Why This Trial Matters Statistically

This study illustrates a central statistical challenge in early-phase research: the purpose may be to characterize safety and guide dose selection, while the available record may offer only sparse descriptive data. A DLT endpoint is directly relevant to dose-finding because it focuses attention on a defined category of treatment-period toxicity. Its interpretation nevertheless depends on a clear event definition, observation window, and decision process. The registry identifies the first-cycle definition and up-to-28-day timeframe, but does not report the numerical primary outcome or the dose-selection method.

The record also shows why safety counts require context. Counts by dose can make the observed events visible, but the study is single group and has no control arm. As a general statistical principle, a count without a comparison does not estimate what would have happened under another treatment or no study treatment. In small dose groups, counts can also be unstable descriptions of underlying event frequency. The registry reports some serious-event information but does not provide uncertainty estimates for the primary DLT outcome.

Another statistical lesson concerns the difference between planned outcomes and reported results. The record names pharmacokinetic measures and ECG change, yet numerical findings for those measures are not reported. Listing an outcome does not establish that it was measured successfully, analyzed, or reported. Similarly, a stated study purpose of determining maximum tolerated dose does not demonstrate that such a dose was identified.

The case also highlights the importance of analysis details for interpreting early-phase studies. Dose assignment, escalation rules, missing-data handling, interim review, and the formal statistical plan all affect how safety findings should be understood. Those details are not reported in the registry record. Their absence leaves uncertainty about how the listed outcomes informed study decisions. The record is still informative about the intended clinical question and the nature of the design, but it cannot support a full quantitative assessment of the primary question.

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 principal limitation is that the numerical result for the primary DLT endpoint is not reported in the registry record. Without that result, readers cannot assess the observed count or its precision, despite the clearly stated endpoint definition and timeframe. A maximum tolerated dose determination is also not reported, even though it is named in the study purpose.

The study is recorded as single group, with no masking and allocation marked NA. There is no concurrent control group for interpreting adverse-event counts against another treatment or background experience. The groups are described by dose, but the registry record does not explain how participants were assigned to dose levels or how dose changes were decided. The arm descriptions do not add further administration details.

The total enrollment is 11, and the reported dose-group sizes are small. Sparse safety data can be imprecise and sensitive to the outcomes of individual participants; this is a general statistical limitation, not an estimate of the amount of uncertainty in this study. The record does not report confidence intervals for the safety counts. Serious adverse-event counts and DLTs should also remain distinct because the primary endpoint has additional criteria for timing and drug relationship.

The registry record does not report the reason the study was terminated, the statistical analysis plan, an interim-analysis approach, the sample-size justification, or how missing data were handled. It lists 17 outcome measures but does not report numerical findings for the primary outcome or the named pharmacokinetic and ECG outcomes. These gaps restrict assessment of the study’s analytic conduct and the completeness of its reported results. The record does not establish causality for the listed adverse events or support comparative efficacy conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of BMS-863233 in Patients With Advanced and/or Metastatic Solid Tumors — NCT00886782.
• Registry record last updated 2023-04-28; status last verified 2023-04.
• Results first posted 2023-04-28.
• 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

NCT00886782 is a phase 1/2, single-group study of BMS-863233 in participants with advanced and/or metastatic solid tumors. The official title describes a multiple ascending dose study of safety, pharmacokinetics, and pharmacodynamics. The registry lists Bristol-Myers Squibb as sponsor, enrollment of 11, and a terminated status. The recorded start date is 2009-05-31, and the primary completion date is 2010-08-04.

The primary outcome is the number of treated participants with DLTs during up to 28 days. DLTs are defined as drug-related adverse events during the first cycle, assessed using NCI CTCAE v3.0. Dose groups are listed as 25 mg, 50 mg, and 100 mg. The registry also lists pharmacokinetic outcomes and change from baseline in mean heart rate by ECG.

Descriptive serious adverse-event counts and deaths are reported by dose group, but the numerical primary DLT result, a maximum tolerated dose determination, and numerical secondary-outcome findings are not reported in the registry record. The reason for termination and further statistical-analysis details are also not reported.