A Safety Study in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety Study in Participants With Advanced Solid Tumors (NCT01284335), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose-Limiting Toxicities Cycle 1.

2. Clinical Question

The registry also lists pharmacokinetic measures, best overall tumor response, and clinically significant effects among the secondary outcomes. Those measures address drug exposure, tumor response, and other safety observations, but they do not replace the primary focus on dose-limiting toxicity during the first treatment cycle. The record describes the study as terminated; it does not report the reason for termination.

3. Trial Design

This was a Phase 1, multicenter, non-randomized, unmasked, parallel study of tasisulam in combination with gemcitabine, docetaxel, temozolomide, cisplatin, or erlotinib. The registry lists enrollment as 234 and identifies advanced solid tumors as the condition. The listed study start is 2008-07, and primary completion is listed as 2012-10. The study status is terminated.

The combinations were organized into separate groups. The registry includes dose-escalation groups for each combination and dose-confirmation groups for gemcitabine, docetaxel, temozolomide, cisplatin, and erlotinib. Some combinations have more than one dose-escalation group in the posted safety data. These are not randomized arms assigned to compare one medicine against another; the registry explicitly identifies the study as non-randomized.

The study's stated purpose was to determine a safe dose of tasisulam when used in the five separate combinations. The registry says that study data would be reviewed for side effects and anti-tumor activity associated with the combinations. The primary endpoint was the number of participants with dose-limiting toxicities during Cycle 1, with a timeframe of baseline to Cycle 1, up to Day 28.

Because there was no randomized allocation, differences between combination groups cannot be interpreted as unbiased estimates of comparative treatment effects. Group membership, dose level, and the reasons participants entered each group may differ; details of those factors are not reported in the registry record. The registry record also does not report the specific dose-escalation rules, the dose selected for confirmation, or the rationale for the study's terminated status. No assumptions about these design features can be made from the posted information.

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.

Before assignment: Study completion was defined as when the recommended dose of LY573636 (tasisulam) was defined for each treatment arm or if a decision was made to stop enrollment in the study for business reasons.

Only the first 6 of 13 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug Tasisulam in dose escalation phase and experienced a dose-limiting toxicity.

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: Participants who received at least one dose of study drug.

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose-Limiting Toxicities Cycle 1, measured over Baseline to Cycle 1 (Up to Day 28).

The primary endpoint is the number of participants with dose-limiting toxicities from baseline through Cycle 1, up to Day 28. The registry defines a dose-limiting toxicity as an adverse event likely related to the study medication or combination that meets one or more specified severity criteria. These include Grade 4 neutropenia lasting more than 5 days; Grade 4 neutropenia with fever or Grade 4 thrombocytopenia regardless of duration; Grade 3 or higher thrombocytopenia with bleeding regardless of duration; or Grade 3 or higher nonhematologic toxicity, with stated exceptions for symptoms that can be controlled with medication and alopecia. Grade 3 electrolyte toxicity is not considered dose-limiting unless it is related to study treatment and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1.

In general, a dose-limiting toxicity endpoint is used in early-phase research to identify serious tolerability concerns within a defined treatment period. It can inform dose evaluation, but a count alone does not describe the full pattern, duration, or severity of all adverse events. The registry's endpoint population is described as participants who received at least one dose of tasisulam during dose escalation and experienced a dose-limiting toxicity. The number of participants evaluated for the primary endpoint, the number meeting its definition, and any dose-level results are not reported in the registry record. The posted safety counts are not a substitute for those missing endpoint results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted information describes a Phase 1, non-randomized, parallel study. No randomized allocation means that the groups cannot be treated as exchangeable by design. In general, randomization helps balance measured and unmeasured participant characteristics across groups; without it, observed group differences may reflect who entered each group, the dose received, or other differences as well as any treatment-related effect. The registry itself cautions that its arms are not a like-for-like control comparison.

What does a participant count measure?

The primary endpoint is a count of participants meeting the dose-limiting toxicity definition during Cycle 1. A participant count is a discrete outcome: it records how many people in an analyzed group had the event, rather than measuring the event's duration or severity as a continuous quantity. To interpret such a count, the number of participants assessed and the rules for inclusion matter. The registry describes the endpoint population as participants who received at least one dose of tasisulam in dose escalation and experienced a dose-limiting toxicity. It does not report the primary endpoint's observed count, the number assessed, or how endpoint data were handled when a participant's status could not be determined.

How is a dose-limiting toxicity defined?

The definition uses adverse-event severity, duration, and clinical features. It includes specified blood-related toxicities, certain nonhematologic toxicities, and a qualification for electrolyte toxicity. Such a definition makes the endpoint more specific than a count of all adverse events: an event must be judged likely related to the study medication or combination and meet at least one listed criterion. In general, a prespecified definition can improve consistency in classification, but the registry record does not report details of event adjudication or how disagreements were resolved.

How should group counts be compared?

In general, comparing event counts requires attention to group size and follow-up, and a formal comparison requires assumptions and an analysis plan. Here, the groups are non-randomized and include different drug combinations and study stages. A raw difference between their counts would not isolate a treatment effect. No new group comparisons should be inferred from the listed counts, and no adjusted estimates or inferential analyses are reported in the registry record. The posted safety numbers are descriptive, not evidence from a randomized head-to-head test.

What does the sample-size illustration represent?

The registry's planning illustration is described as based on an observed effect, not on the trial's own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations ask how many participants a hypothetical future comparison might require under selected assumptions. They do not show that the actual study was planned or conducted with those assumptions, and they are not observed power. The record does not give the numerical planning outputs in the information analyzed here, and the non-randomized combination groups do not form a direct randomized comparison.

What statistical results are available?

The registry lists 0 analyses. It does not report inferential estimates, confidence intervals, hypothesis tests, or adjusted treatment comparisons for the primary endpoint. In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis; it is not a guarantee that the true value lies within its limits. Without an endpoint estimate and its uncertainty, the precision of the primary result cannot be assessed. The registry's adverse-event counts and percentages remain descriptive observations, and they should not be read as statistically tested differences between combinations.

Similarly, the secondary outcome list identifies pharmacokinetic measures, tumor response, and clinically significant effects, but the listed outcomes alone do not establish their results. No additional analyses, model choices, or estimation procedures should be inferred. The registry record does not report the statistical plan, analysis populations beyond the stated primary endpoint population, or procedures for interim analyses. Those omissions limit assessment of whether the intended analyses, if any, were followed.

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("Arm A Tasisulam + Gemcitabine Dose Escalation", "Arm A Tasisulam + Gemcitabine Dose Confirmation", "Arm B* Tasisulam + Docetaxel Dose Escalation", "Arm B1 Tasisulam + Docetaxel Dose Escalation", "Arm B2 Tasisulam + Docetaxel Dose Escalation", "Arm B2 Tasisulam + Docetaxel Dose Confirmation")
n      <- c(25, 33, 5, 5, 24, 26)
events <- c(4, 0, 4, 4, 3, 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  Arm A Tasisulam + Gemcitabine Dose Escalation  25  4  16.0  4.5  36.1  6.4  34.7  6.6  34.9
ARM  Arm A Tasisulam + Gemcitabine Dose Confirmation  33  0  0.0  0.0  10.6  0.0  10.4  0.1  10.3
ARM  Arm B* Tasisulam + Docetaxel Dose Escalation  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  Arm B1 Tasisulam + Docetaxel Dose Escalation  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  Arm B2 Tasisulam + Docetaxel Dose Escalation  24  3  12.5  2.7  32.4  4.3  31.0  4.5  31.2
ARM  Arm B2 Tasisulam + Docetaxel Dose Confirmation  26  0  0.0  0.0  13.2  0.0  12.9  0.1  12.8

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary safety endpoint alongside secondary outcomes covering pharmacokinetics, tumor response, and clinically significant effects. It also includes five different medication combinations and separate dose-escalation and dose-confirmation groups. In general, examining several outcomes or groups creates multiple opportunities to observe apparently notable results by chance. A prespecified multiplicity strategy can help control that issue when formal hypothesis tests are conducted.

The registry record does not report a statistical analysis plan, a multiplicity adjustment, a hierarchy of secondary outcomes, or inferential analyses; it lists 0 analyses. It is therefore not possible to determine whether formal testing was planned or how any family of comparisons would have been handled. The posted group counts should be interpreted descriptively, not as a set of statistically confirmed comparisons.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint description identifies participants who received at least one dose of tasisulam during dose escalation and experienced a dose-limiting toxicity, but it does not report the full denominator assessed, how participants without a complete Cycle 1 observation were handled, or whether all treated participants were included in endpoint summaries. The adverse-event groups have their own reported at-risk counts, but those do not resolve missingness for the primary endpoint.

In general, incomplete observation can affect event counts if participants leave observation early or have an unrecorded outcome. The registry does not state whether such situations occurred or how they were addressed. Without those details, the completeness and analysis-population basis of the primary endpoint cannot be assessed. No assumption about missing-data handling or multiplicity procedures is justified by the posted record.

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: urinary tract infection (25.0%), febrile neutropenia (20.0%), thrombocytopenia (20.0%), atrial fibrillation (20.0%), neutropenic sepsis (20.0%).

The safety data are reported separately for dose-escalation and dose-confirmation groups, with group-specific numbers at risk, serious adverse events, other adverse events, and deaths. Read each count within its own group and reporting category. The record does not support combining groups into a single study-wide count or treating the groups as direct comparisons. Their combinations and study stages differ, and allocation was non-randomized.

The serious-event terms listed include urinary tract infection at 25.0%; febrile neutropenia, thrombocytopenia, atrial fibrillation, neutropenic sepsis, and hypokalaemia are each listed at 20.0%. These percentages describe the registry's reported term list. The record does not provide enough accompanying information to determine from that list alone how the percentages relate to the group-level counts or to compare the terms across combinations.

Serious adverse events are not interchangeable with dose-limiting toxicities. A serious event may not meet the primary endpoint's specific criteria, and a dose-limiting toxicity requires the stated relationship and severity conditions. Deaths are recorded by group, but their causal relationship to study medication is not reported in the information. The safety figures describe events recorded during the study; they do not by themselves establish causation, comparative risk, or a treatment effect.

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

The posted record establishes that this Phase 1 study evaluated tasisulam in five separate medication combinations and collected safety information across dose-escalation and dose-confirmation groups. It defines a primary endpoint focused on dose-limiting toxicities during the first treatment cycle and records adverse-event counts by group. These features make the study relevant as an early-phase safety assessment, where the central statistical task is to describe tolerability and evaluate dose-related concerns.

The record does not report the primary endpoint result, an endpoint denominator, a dose-selection conclusion, or statistical uncertainty for that endpoint. The listed serious adverse events and deaths should therefore be interpreted as recorded safety observations, not as a complete analysis of the primary question. The registry does not identify the deaths as treatment-related, and the group-level data do not establish that a particular medication combination caused the reported events.

The design also limits comparative interpretation. The study was non-randomized, and its groups involve different combinations and study stages. A difference in counts across those groups could reflect differences in participants, dose, or observation, rather than a difference attributable to the combination itself. There is no like-for-like randomized control comparison in the registry record.

Nothing in these descriptive data establishes whether a combination is effective or ineffective. Although tumor response is listed as a secondary outcome, the registry information does not report a complete response analysis. Nor can unreported results be inferred from the adverse-event summaries. The appropriate conclusion is narrow: the record documents the study design and selected safety observations, but does not provide the primary endpoint result or analyses needed to draw stronger statistical conclusions.

14. Why This Trial Matters Statistically

This study illustrates a recurring statistical challenge in early-phase combination research: safety information is collected across several treatment combinations, while the groups are not randomized against one another. A reader must distinguish an early safety description from a comparative treatment-effect estimate. The study's stated aim was to determine a safe dose of tasisulam with each of five approved cancer medications, and its primary endpoint focused on dose-limiting toxicities during Cycle 1.

The endpoint's definition shows why careful outcome specification matters. It relies on event severity, duration, relationship to study medication, and exceptions for particular toxicities. These criteria make the endpoint more focused than a general adverse-event tally. At the same time, the registry record does not report the number meeting this definition or the number assessed, so readers cannot evaluate the primary endpoint's magnitude or precision.

The study also demonstrates why arm labels and counts do not by themselves establish a comparison. Dose-escalation and dose-confirmation groups serve different roles, and non-random allocation does not ensure comparable participants across groups. Treating the groups as controls for one another would overstate what the design can show. The registry's warning that the arms are not a like-for-like control comparison is central to interpreting the posted safety data.

Finally, a registry record can identify intended outcomes and report selected event counts without reporting a complete statistical analysis. Here, the analysis count is listed as 0, and the primary result, analysis plan, missing-data procedures, and multiplicity approach are not reported. These gaps matter because they constrain both reproducibility and the strength of conclusions readers can draw. The example underscores that transparent endpoint results, denominators, and analysis methods are necessary to interpret early-phase safety data responsibly.

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 most important limitation is that the registry record does not report the primary endpoint count or the number of participants assessed for dose-limiting toxicity. Although the endpoint definition and timeframe are stated, its observed result and statistical uncertainty are unavailable. A conclusion about dose-limiting toxicity or dose selection cannot be drawn from the endpoint description alone.

The non-randomized design limits comparisons across the separate combination groups. Differences in participant characteristics, dose, or study stage may affect the observed counts, and those factors are not described in enough detail to adjust for them. The record itself states that the arms are not a like-for-like control comparison. It also does not report the reason the study was terminated.

The registry lists group-specific safety counts, but the information does not establish a causal relationship for each event or death. Serious adverse events, other adverse events, deaths, and dose-limiting toxicities represent different categories; they should not be conflated. The serious-event term percentages are not accompanied by enough context in the record to support a comparative interpretation.

Further limitations include the absence of reported inferential analyses, confidence intervals, a statistical analysis plan, missing-data procedures, and multiplicity methods. The registry lists 0 analyses. The status of secondary outcome results is also limited in the record, despite their inclusion in the outcome list. These omissions prevent assessment of the precision, completeness, and analysis-population basis of the reported findings. The registry does not report details of dose-escalation rules or the dose selected for confirmation, so those aspects cannot be evaluated.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety Study in Participants With Advanced Solid Tumors — NCT01284335.
• Registry record last updated 2019-01-10; status last verified 2018-12.
• Results first posted 2018-10-16.
• 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

The registry describes a Phase 1, multicenter, non-randomized, unmasked, parallel study of tasisulam combined separately with gemcitabine, docetaxel, temozolomide, cisplatin, or erlotinib in participants with advanced solid tumors. Enrollment is listed as 234. The study is marked terminated, with a listed start of 2008-07 and primary completion of 2012-10.

The primary endpoint is the number of participants with dose-limiting toxicities from baseline through Cycle 1, up to Day 28. The registry defines the toxicity criteria but does not report the primary endpoint result or its denominator. Group-specific adverse-event counts and selected serious-event terms are reported descriptively. The design does not support like-for-like comparisons across combinations, and the registry lists 0 analyses. The reason for termination, statistical plan, and missing-data methods are not reported in the registry record.