An Open-Label Study of Ruxolitinib Given With Chemotherapy in Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Study of Ruxolitinib Given With Chemotherapy in Patients With Advanced Solid Tumors (NCT01822756), a non-randomized phase 1 study. The primary outcome is Percentage of Participants With Adverse Events That Are Defined as Dose Limiting Toxicities (DLTs).

2. Clinical Question

The central statistical question is therefore one of early-phase tolerability assessment, not a comparative efficacy question. The planned approach used dose cohorts to assess whether the combination could be given within the study’s specified tolerability criteria. Such a design can describe observed toxicities in the enrolled participants, but without random allocation it cannot isolate the effect of ruxolitinib from chemotherapy, participant characteristics, or other differences between cohorts.

The record names preliminary clinical activity and tumor response among secondary outcomes. However, it says that computed tomography for tumor burden was collected but not analyzed, and analysis data are not available. It also says pharmacokinetic and pharmacodynamic samples were collected but not analyzed. As a result, the registry record does not support a numerical account of tumor response, drug exposure, or biomarker changes.

3. Trial Design

The registry classifies the study as phase 1, non-randomized, unmasked and single-group; the official title describes it as a phase 1b study. It lists an enrollment of 42. The study began in 2013-04, had primary completion in 2015-09, and is marked terminated. These design features place the record in the context of early development and safety assessment rather than a randomized comparison of treatment strategies.

The study had two planned parts. Part 1 was intended to evaluate safety, tolerability and pharmacokinetics and to identify the maximally tolerated dose of ruxolitinib when combined with gemcitabine with or without nab-paclitaxel. That dose was intended for evaluation in Part 2, which was planned to assess safety, tolerability, pharmacokinetics and preliminary clinical activity. The registry record says the study ended early after challenges in trial conduct, by mutual agreement between investigators and sponsor. Dose escalation stopped after Cohort B1, RUX 10 mg twice daily (BID) - GCSF, in October 2014. The maximally tolerated dose was not reached.

The named regimens vary in chemotherapy and filgrastim use, and the record lists cohorts A0, B (-1), B0 (+GCSF), B0 (-GCSF) and B1 in its adverse-event figures. Because treatment was not randomized, those cohorts are not interchangeable control groups. Their results may reflect regimen differences, dose level, or the order and circumstances in which cohorts were enrolled. The registry record does not report the full cohort assignment process, dose-escalation rules, or statistical plan.

No safety issues led to the decision to stop further enrollment, according to the registry summary. That statement describes the reported reason for stopping, not a conclusion that the regimens were free of safety concerns. The record gives no efficacy analysis results and no completed dose-finding conclusion.

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 included all enrolled subjects who received at least 1 dose of RUX.

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: Intent-to-Treat Subjects (ITT): All subjects who received at least 1 dose of Ruxolitinib (RUX).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Events That Are Defined as Dose Limiting Toxicities (DLTs), measured over Approximately 28 days.

The primary endpoint was the percentage of participants with adverse events defined as dose-limiting toxicities (DLTs). It was assessed over approximately 28 days, described as the first treatment cycle. In an early-phase dose-escalation study, a DLT endpoint is used to identify treatment-limiting toxicity within a specified observation period and to inform decisions about which dose level to study further.

The registry describes who could be considered evaluable within a cohort: a participant had to receive at least 40 of 56 planned ruxolitinib doses during the 28-day surveillance period and receive 2 of the 3 planned chemotherapy doses at the assigned dose level, or experience a DLT. The safety population was defined separately as all enrolled participants who received at least 1 dose of ruxolitinib. These definitions matter because the set included in a safety summary need not be identical to the set evaluable for the DLT endpoint.

The registry record does not report the number or percentage of participants with DLTs, nor does it provide a cohort-level DLT result. The serious adverse-event figures listed in the record are not a substitute for that endpoint: a serious adverse event and a DLT are distinct classifications, and the record does not state that the listed serious events were DLTs. Without the endpoint result, the observed DLT frequency and its precision cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a percentage, so its basic statistical meaning is the share of an analysis population meeting a defined event criterion. Here, the criterion was an adverse event classified as a dose-limiting toxicity during approximately 28 days. A percentage is informative only when its numerator and denominator are clear: the numerator is the participants meeting the endpoint definition, and the denominator is the participants included in that endpoint analysis. The registry describes population and evaluability rules, but it does not report a DLT numerator, endpoint denominator, or resulting percentage.

What does a dose-limiting toxicity endpoint capture?

In general, DLT endpoints are designed to focus attention on toxicities during a prespecified early observation period, when dose escalation decisions are being made. The endpoint is not necessarily a count of every adverse event: it depends on which events meet the DLT definition. The registry record gives dose-administration conditions for evaluability, but it does not report the event-level DLT definition or the endpoint outcome. A reader should not substitute the serious adverse-event list for a DLT result, because seriousness and dose-limiting status are not equivalent classifications.

How should the cohort structure be understood?

The record identifies several cohorts with differing regimen labels and reports adverse-event counts separately for them. In general, cohort-specific summaries can help describe what was observed in participants treated under each cohort’s conditions. They do not automatically support a causal comparison. Randomization is one way to make treatment groups more comparable on average; this study was non-randomized and single-group. The registry explicitly cautions that its arms are not a like-for-like control comparison. Thus, apparent differences across cohort counts can reflect regimen or dose differences and other differences in who entered each cohort, rather than an isolated treatment effect.

For a binary outcome such as whether a participant experienced an event, statistical precision depends in part on the number of people contributing to the analysis and the event frequency. In general, a confidence interval describes a range of values compatible with the observed data under a stated method. Narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. The registry record does not report a DLT estimate or interval, so neither its magnitude nor its precision can be assessed.

What can planning calculations tell a reader?

In general, a sample-size planning illustration asks how many participants per arm might be needed under specified assumptions to detect a target effect with a chosen significance level and power. Such an illustration is not an observed result, and it does not demonstrate the power achieved by a completed study. The planning assumptions recorded for this study describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not change the fact that this was not a randomized two-arm comparison. The registry record does not report a trial-specific sample-size justification, and the planning illustrations should not be mistaken for the study’s design rationale or actual statistical power.

In general, observed-effect-based planning can be sensitive to uncertainty in the initial effect estimate. If that estimate is imprecise, a planning result based on it can also be unstable. Planning outputs are therefore conditional illustrations rather than forecasts or evidence of treatment benefit. No new sample-size estimate can be inferred from the registry text alone.

What does early termination change?

Early termination can leave planned analyses incomplete, reduce the information available for estimating event rates, and prevent a dose-escalation objective from being resolved. In this record, the registry explicitly says that the maximally tolerated dose was not reached. It also says that pharmacokinetic and pharmacodynamic samples and computed tomography for tumor burden were collected but not analyzed. Collection is not the same as an analyzed result: without analysis data, those measures cannot support statistical conclusions about exposure, biomarkers or tumor change.

The record lists zero analyses in its posted analysis count. That absence is consistent with the limited results described in the summary, but it should not be expanded into a claim about every analysis that may have been considered outside the registry. The statistical plan, including any interim analysis procedures, is not reported in the registry record. The handling of missing endpoint data is also not reported in the registry record.

Why are denominators important?

Different endpoints can use different analysis populations. The safety population included enrolled participants who received at least 1 dose of ruxolitinib. The primary endpoint’s evaluability description additionally specifies treatment exposure during the surveillance period or a DLT. These definitions answer different questions. A safety summary can include participants who do not meet a particular endpoint’s evaluability criteria, while endpoint-specific denominators can be affected by incomplete treatment or follow-up. Since the DLT result and its denominator are absent, the registry record does not permit a reconstruction of the primary endpoint analysis.

In general, missing outcomes can affect interpretation when the likelihood of missingness is related to participant health, treatment exposure or observed outcomes. Statistical methods can address missing data only under assumptions that need to be stated and assessed. The registry record does not report how missing primary endpoint information was handled or what assumptions were used.

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 A0", "Cohort B (-1)", "Cohort B0 (+GCSF)", "Cohort B0 (-GCSF)", "Cohort B1")
n      <- c(16, 4, 10, 4, 8)
events <- c(0, 0, 2, 2, 0)
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 A0  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5
ARM  Cohort B (-1)  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Cohort B0 (+GCSF)  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8
ARM  Cohort B0 (-GCSF)  4  2  50.0  6.8  93.2  15.0  85.0  14.7  85.3
ARM  Cohort B1  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including pharmacokinetic measures, biomarkers and cytokines, tumor burden, response measures and duration of response. It does not report analysis results for these outcomes. Because multiple outcomes can raise the chance of finding an apparently notable result by chance when many hypotheses are tested, general statistical practice is to prespecify how multiplicity will be handled. A multiplicity strategy is not reported in the registry record. The statistical analysis plan and any interim-analysis procedures are also not reported in the registry record.

Missingness is especially relevant because the study ended early. The registry says pharmacokinetic and pharmacodynamic samples and computed tomography for tumor burden were collected but not analyzed; analysis data are not available. This is different from reporting analyzed outcomes that happen to be missing for some participants. The record does not describe endpoint-specific missingness, reasons for missing primary endpoint data, or any imputation or sensitivity analyses.

The primary endpoint specifies a safety population of enrolled participants who received at least 1 dose of ruxolitinib, and separately describes evaluability for DLT assessment. The registry does not provide the number analyzed for the DLT endpoint or explain how participants who did not meet evaluability conditions were handled. Therefore, the endpoint denominator and any consequences of incomplete exposure or follow-up cannot be assessed.

The registry lists zero analyses in its analysis count. No inferential results, multiplicity adjustments, or missing-data analyses are reported in the registry record. Any assumption about how those issues were addressed would be speculative.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (25.0%), abdominal pain (25.0%), duodenal ulcer hemorrhage (25.0%), asthenia (25.0%), pharyngeal abscess (25.0%).

The serious adverse-event figures are presented by cohort as counts of participants at risk and counts affected. Cohort A0 lists 10 affected among 16 at risk; Cohort B (-1) lists 4 among 4; Cohort B0 (+GCSF) lists 3 among 10; Cohort B0 (-GCSF) lists 0 among 4; and Cohort B1 lists 2 among 8. These are descriptive cohort summaries, not randomized comparisons.

The registry also lists the serious terms anemia, abdominal pain, duodenal ulcer hemorrhage, asthenia, pharyngeal abscess and urinary tract infection, each at 25.0%. The record does not give further event-level detail alongside those terms, so they should not be interpreted as rates of DLTs or as evidence about comparative risk.

Other adverse-event figures list all participants in each cohort as affected: 16 of 16 in Cohort A0, 4 of 4 in Cohort B (-1), 10 of 10 in Cohort B0 (+GCSF), 4 of 4 in Cohort B0 (-GCSF) and 8 of 8 in Cohort B1. These counts should be kept distinct from the serious adverse-event figures. The registry does not provide a causal comparison, a DLT classification for these events, or detail sufficient to attribute events to a particular treatment component.

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

The record establishes that an early-phase study of ruxolitinib with chemotherapy was conducted in advanced or metastatic pancreatic cancer and that it ended before the planned dose-finding aim was completed. Dose escalation stopped after Cohort B1, and the registry states that the maximally tolerated dose was not reached. This is the key limit on what can be concluded about the dose-escalation objective.

The primary endpoint focused on dose-limiting toxicities during approximately 28 days. Its result is not reported in the registry record. The listed serious adverse-event counts describe events by cohort, but they do not establish the DLT frequency. Nor do they establish whether a particular regimen caused an event, because there was no randomized control group and the cohorts were not like-for-like comparisons.

The record says that no safety issues led to stopping further enrollment. This reports the stated reason for ending the study; it does not mean that no adverse events occurred. Serious adverse events and other adverse events are listed, and the primary endpoint result remains unavailable.

The study’s planned secondary assessments included pharmacokinetics, pharmacodynamics and preliminary clinical activity. The registry says collected samples and tumor imaging were not analyzed, and analysis data are not available. Therefore, this record does not establish a treatment effect on tumor burden, response, survival, biomarkers or drug exposure. It also does not support a conclusion about efficacy.

In general, early-phase studies can provide descriptive safety and dose-finding information, but interpretation depends on completed endpoint analyses and the design used. Here, early termination and missing analyses leave the central dose-finding question unresolved. The posted information is best read as a record of the study’s conduct, its endpoint definitions and the adverse-event summaries that were reported, rather than as a completed evaluation of safety or clinical activity.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a planned endpoint and a reported result. The registry describes a DLT percentage as the primary endpoint and gives criteria for endpoint evaluability, but does not report the endpoint estimate. A clear endpoint definition is useful, yet without its result and denominator the reader cannot assess either the observed frequency or its precision.

It also shows why dose-finding status should be reported directly. The study’s stated goal included identifying a maximally tolerated dose, but dose escalation ended after Cohort B1 and the registry says the maximally tolerated dose was not reached. Treating the last cohort studied as if it were a completed dose-finding conclusion would overstate what the record establishes.

The study’s non-randomized, single-group structure is another important statistical feature. Cohort-specific adverse-event counts can describe what was recorded in each cohort, but they do not offer a like-for-like treatment comparison. The registry itself warns against treating the arms as comparable controls. This is particularly important when regimen components differ among cohorts.

Finally, the record distinguishes between data collection and analysis. Pharmacokinetic and pharmacodynamic samples and tumor imaging were collected, but not analyzed. Collected material cannot be interpreted as an outcome result without analysis. These gaps make the record useful for understanding study design and the limits of the available safety summaries, while leaving major planned questions unresolved.

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 registry record reports early termination after challenges of trial conduct and says the maximally tolerated dose was not reached. This limits interpretation of the planned dose-escalation objective. It does not provide the primary DLT result, its analysis denominator, or a precision estimate.

The study was non-randomized and single-group. Cohort-level adverse-event counts therefore should not be interpreted as controlled estimates of differences between treatment strategies. The regimens varied, and the record does not report enough detail to isolate the contribution of individual treatment components.

Several planned secondary outcomes cannot be evaluated from the record. Pharmacokinetic and pharmacodynamic samples and computed tomography for tumor burden were collected but not analyzed. Analysis data are unavailable. The record does not report a statistical analysis plan, interim-analysis methods, multiplicity handling, or missing-data methods. The criteria for DLT evaluability are described, but the corresponding endpoint result is absent.

The registry summary says no safety issues led to the decision to stop further enrollment. That statement does not replace a complete safety analysis and does not imply the absence of adverse events. The record lists serious adverse events and other adverse-event counts, but does not link those counts to the DLT endpoint. These limitations make it inappropriate to infer a completed safety or efficacy conclusion from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Study of Ruxolitinib Given With Chemotherapy in Patients With Advanced Solid Tumors — NCT01822756.
• Registry record last updated 2018-02-12; status last verified 2018-01.
• Results first posted 2017-04-13.
• 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 is a phase 1, non-randomized, single-group study of ruxolitinib with gemcitabine, with or without nab-paclitaxel, in advanced or metastatic pancreatic cancer. Filgrastim was included in a named regimen. The registry lists enrollment of 42 and marks the study terminated.

The primary endpoint was the percentage of participants with DLTs during approximately 28 days. Its result is not reported in the registry record. Dose escalation ended after Cohort B1, and the maximally tolerated dose was not reached. The record reports serious adverse-event counts by cohort, but these are not DLT results or randomized comparisons.

Planned pharmacology and tumor assessments were collected but not analyzed, and analysis data are unavailable. The registry states that no safety issues led to the decision to stop further enrollment.