A Study of Tasisulam in Treating Participants With Malignant Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tasisulam in Treating Participants With Malignant Melanoma (NCT00383292), a na phase 2 study. The primary outcome is Percentage of Participants Achieving Objective Response Rate (ORR) (Complete Response + Partial Response).

2. Clinical Question

The study was a phase 2 investigation in participants with metastatic melanoma, with an enrollment of 130. Its stated purpose was to assess objective response after one prior systemic treatment for unresectable or metastatic disease. The endpoint is a measure of tumor response under the registered response criteria; it is not a comparison against an untreated group or another treatment group.

The registry also lists secondary outcomes covering progression-free survival, overall survival, clinical response including stable disease, pharmacokinetics, response and stable-disease duration, serious adverse events considered related to study drug, and health-related quality of life. These outcomes describe additional domains of interest, but their result values are not reported in the registry record. Accordingly, the clinical question can be stated from the protocol description, but the recorded information does not establish the observed response rate or the pattern of the other outcomes.

3. Trial Design

This completed phase 2 study examined tasisulam in participants with unresectable or metastatic melanoma after one prior systemic treatment. The registry lists an enrollment of 130 and describes the primary endpoint population as participants who received at least one dose of study drug. The study started in 2006-11 and its primary completion date is listed as 2011-09.

The design is recorded as single-group, with allocation listed as not applicable and masking as none. The registry lists three treatment groups: Tasisulam Dose Target 420 μg/mL Cmax, Tasisulam Dose Target 360 μg/mL Cmax, and Tasisulam Albumin-Tailored Dose. Their recorded participant counts at risk for serious adverse events are 68, 32, and 30, respectively. These categories do not establish a randomized treatment comparison. The registry explicitly cautions that the arms are not a like-for-like control comparison.

The official title describes tasisulam, also identified there as LY573636, as an intravenous infusion on Day 1 of a 28-day cycle. The registry’s brief summary states that the primary purpose was to determine objective response after one prior systemic treatment. The primary endpoint timeframe is described as baseline to measured progressive disease, up to 60 months.

The primary endpoint was the percentage achieving objective response, where response means a best overall response of complete response or partial response. The registry lists a 90% confidence interval for this endpoint’s dispersion, but it does not report an endpoint estimate or interval limits. No analysis results are listed in the record. Details such as a randomization procedure, a comparative control arm, or a fuller statistical analysis plan are not reported in the registry record.

Secondary outcomes include time-to-event, response-duration, safety, pharmacokinetic, and quality-of-life measures. Their presence in the outcome list indicates what the study planned to assess, not that results for each measure are available in the record. The dose groups should therefore be read as study treatment categories, not as evidence of a controlled head-to-head evaluation.

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 a participant completing 2 cycles of treatment and end of Cycle 2 radiographic assessment of response.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug.

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: All enrolled participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Objective Response Rate (ORR) (Complete Response + Partial Response), measured over Baseline to Measured Progressive Disease (up to 60 Months).

The primary endpoint is the percentage of participants who achieved an objective response. A participant counts as an objective responder if their best overall response was complete response or partial response, according to the registry’s description of RECIST v1.1. Complete response requires disappearance of all non-nodal target lesions, reduction of target lymph-node short axes to <10 mm, disappearance of non-target lesions, and normalization of tumor marker levels when those levels were initially above the upper limit of normal. Partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference.

A response percentage is a binary-outcome summary: each participant is classified as having met or not met the response definition for the analysis. Such an endpoint offers a direct way to describe the proportion of treated participants with tumor shrinkage meeting specified criteria. It does not by itself describe how long a response lasted, whether disease remained stable, or how survival changed; those are distinct outcomes listed separately in this record.

The endpoint timeframe is baseline to measured progressive disease, up to 60 months, and the stated population includes participants who received at least one dose. The registry specifies a 90% confidence interval, but reports neither the observed response percentage nor the interval limits. The endpoint definition is therefore available, while the numerical result and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome summarized as a percentage. Each participant is classified according to whether their best overall response meets the registry’s definition of objective response: complete response or partial response. The response criteria described in the record are based on RECIST v1.1. No numerical primary endpoint result is reported in the registry record.

What does a response percentage represent?

In general, a percentage for a binary outcome summarizes the share of the analysis population assigned to the event category. For this endpoint, the event category is objective response. The percentage is meaningful only alongside a clear denominator, a defined assessment window, and consistent rules for classifying participants. The record identifies the endpoint population as all participants who received at least one dose and gives a timeframe of baseline to measured progressive disease, up to 60 months. The number analyzed and the treatment of participants without an evaluable assessment are not reported in the registry record.

Complete response and partial response are distinct response categories, but the primary endpoint combines them. The registry describes complete response as disappearance of all non-nodal target lesions, target lymph-node short axes reduced to <10 mm, disappearance of non-target lesions, and normalization of tumor marker levels when initially above the upper limit of normal. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, with the baseline sum as reference. These criteria supply operational rules for classifying response; they do not themselves indicate how many participants met them.

Why report a confidence interval?

General statistical context: a confidence interval communicates uncertainty in an estimate, rather than giving only a single point estimate. For a response percentage, it helps readers judge how precisely the observed percentage has been estimated under the analysis method. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry specifies a 90% confidence interval for the primary endpoint, but its bounds and the point estimate are not reported. No assessment of precision is therefore possible from the record.

The confidence interval’s level is not a substitute for its limits. Knowing that the registry named a 90% interval does not reveal where the interval lies or how wide it is. Nor does an interval alone resolve issues of bias, representativeness, or comparison: those depend on the design, conduct, and analysis as well as the estimate’s uncertainty.

How does the design affect interpretation?

The registry records a single-group design, no masking, and allocation as not applicable. Three tasisulam dose categories are listed, but the record warns that they are not a like-for-like control comparison. General statistical context: a controlled comparison is needed to separate a treatment contrast from differences that may arise from participant characteristics, selection, follow-up, or other factors. A single-group description can report outcomes among treated participants, but it does not by itself estimate what would have happened under a different treatment or no treatment.

The registry’s dose-group counts at risk for serious adverse events are 68 for the 420 μg/mL Cmax target, 32 for the 360 μg/mL Cmax target, and 30 for the albumin-tailored dose. These are safety-group counts, not a reported primary-outcome denominator. The record does not establish that the three categories were assigned randomly or that comparisons among them were planned as controlled tests. Such design and analysis details are not reported in the registry record.

What can be said about planning calculations?

General statistical context: a sample-size planning illustration asks how many participants might be needed under stated assumptions about a target effect, significance level, allocation, and statistical approximation. It is not an observed outcome and does not tell how likely the trial was to detect an effect after the study is completed. The planning illustrations associated with the posted material are described as based on an observed effect, with equal allocation between two arms and a normal approximation. They are not the trial’s own design justification. The registry record does not report its original sample-size rationale.

Planning calculations that use a fraction of an observed effect are hypothetical scenarios. Their results depend on the assumed effect and other model choices, and they should not be read as observed power. This distinction is especially important for a single-group study, because the planning illustration’s two-arm assumptions do not transform the trial into a randomized comparison. The registry’s allocation and design descriptions remain the basis for interpreting the study.

What other methods details are unavailable?

The registry lists nine outcome measures and no analysis results. It does not report a complete statistical analysis plan, interim analyses, the method used to calculate the primary confidence interval, or how missing assessments were handled. Details on censoring are described for duration of tumor response: participants not known to have died or had objective progression by a particular analysis cut-off were to be censored at their last objective tumor assessment before that cut-off. That description concerns duration of response and does not provide the missing primary response result.

General statistical context: time-to-event endpoints and binary response endpoints answer different questions. A time-to-event measure uses the timing of an event and may involve censoring when the event is not observed during follow-up. A binary response endpoint instead classifies participants according to a response status. The record lists progression-free survival and overall survival as secondary outcomes, but their numerical results and analysis details are not reported in the registry record. Consequently, the methods description can clarify endpoint concepts and design constraints, but it cannot reconstruct unreported analyses.

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("Tasisulam Dose Target 420 μg/mL Cmax", "Tasisulam Dose Target 360 μg/mL Cmax", "Tasisulam Albumin-Tailored Dose")
n      <- c(68, 32, 30)
events <- c(7, 2, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Tasisulam Dose Target 420 μg/mL Cmax  68  7  10.3  4.2  20.1  5.1  19.8  5.1  19.8
ARM  Tasisulam Dose Target 360 μg/mL Cmax  32  2  6.2  0.8  20.8  1.7  20.1  1.9  20.2
ARM  Tasisulam Albumin-Tailored Dose  30  2  6.7  0.8  22.1  1.8  21.3  2.0  21.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary objective response endpoint and multiple secondary outcomes: progression-free survival, clinical response including complete response, partial response, or stable disease, plasma clearance rate, overall survival, duration of overall objective response, duration of stable disease, related serious adverse events, and FACT-G score. The record does not report how inference across these outcomes was managed, whether any outcomes were prioritized beyond their listed status, or whether adjustment for multiple testing was planned. Those details are not reported in the registry record.

General statistical context: when many outcomes are examined, the chance of at least one apparently notable result can increase if each is assessed separately without accounting for the number of tests. A prespecified hierarchy or multiplicity adjustment can address some of this issue, but neither should be assumed without documentation. The presence of numerous outcomes alone does not show that a particular adjustment was or was not used.

The record also does not report how missing response assessments, withdrawals, or participants without an evaluable best response were treated in the primary analysis. Although the endpoint population is described as participants who received at least one dose, the analyzed denominator is not reported. It is therefore not possible to establish from this record whether all treated participants contributed to the endpoint estimate or how incomplete follow-up affected it.

Some duration-of-response censoring rules are described: for a particular analysis cut-off, a participant not known to have died or experienced objective progression was to be censored at their last objective tumor assessment before that cut-off. This is a stated rule for duration of tumor response, not a complete account of missing-data handling across all endpoints. The registry record does not report interim analyses or a complete 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: neutropenia (13.3%), thrombocytopenia (13.3%), pneumonia (10.0%), anaemia (7.4%), hypotension (4.4%).

The registry lists serious adverse event counts for three tasisulam dose categories. The 420 μg/mL Cmax target group had 68 participants at risk and 24 affected; the 360 μg/mL Cmax target group had 32 at risk and 13 affected; the albumin-tailored dose group had 30 at risk and 11 affected. These figures describe recorded serious adverse events within the listed groups. They should not be treated as comparative estimates of risk between groups: the design is single-group, and the registry cautions that the arms are not a like-for-like control comparison.

The listed serious adverse event terms and percentages are neutropenia, 13.3%; thrombocytopenia, 13.3%; pneumonia, 10.0%; anaemia, 7.4%; hypotension, 4.4%; and leukopenia, 3.3%. The registry also lists a secondary outcome for serious adverse events considered by the investigator to be related to study drug. The record does not establish that the group-level affected counts above use that same relatedness restriction, so the counts and the related-event outcome should not be conflated.

The record does not report death counts for these groups. It also does not provide, in the information available, enough detail to determine the duration of safety follow-up or the rules used for attributing events. These figures describe reported safety events, not a controlled comparison or a causal conclusion.

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

The record establishes that a completed phase 2, single-group study was designed to assess objective response to tasisulam in participants with unresectable or metastatic melanoma after one prior systemic treatment. It defines objective response as complete response or partial response under RECIST v1.1 and specifies a 90% confidence interval for the primary endpoint. It does not report the primary response estimate or the interval limits.

Therefore, the posted information does not establish how many participants achieved objective response, how precise any estimate was, or how the study outcome compared with another treatment. The absence of a reported result is not evidence that no responses occurred, nor does it establish a positive or negative outcome. The endpoint definition describes what was to be counted; it is not itself a finding.

The study’s single-group design and lack of masking are important context. The registry lists three dose categories, but explicitly warns that they are not a like-for-like control comparison. These groups cannot be treated as randomized treatment arms on the basis of this record. Any differences among their counts would not, by themselves, establish that a dose caused a difference in outcome.

The registry includes secondary outcomes spanning survival, response duration, stable disease, pharmacokinetics, safety, and quality of life. Their listing indicates the outcomes of interest, but their numerical results are not reported in the registry record. The serious adverse event counts and listed terms can be described as recorded events, with the caveat that the group counts are not a controlled comparison and their relationship to the separate related-event outcome is not established in the record.

General statistical context: statistical evidence and clinical meaning are not interchangeable. An estimate and its uncertainty can describe the data under an analysis, while interpretation also depends on study design, measurement, missingness, and the relevance of the endpoint. Because the primary estimate, confidence interval, and detailed analysis methods are absent, the record supports a description of the question and design, not a conclusion about treatment effect or comparative benefit.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clearly defined endpoint and a study design must be considered together. The primary endpoint has an operational definition: complete or partial response under RECIST v1.1, summarized as a percentage among participants who received at least one dose. That definition makes the intended event measurable, but the registry record does not report the numerical result needed to interpret its frequency or precision.

The single-group design also illustrates the distinction between describing outcomes and estimating comparative effects. A study can record response and safety among treated participants without including a like-for-like control group. Here, the registry specifically cautions that its three tasisulam dose categories are not such a comparison. The design label and the registry’s caution should shape interpretation more than the mere presence of multiple dose categories.

Reporting the confidence interval level without its estimate or limits shows why methods information and results information serve different purposes. The 90% interval was part of the registered endpoint description, but it does not reveal the observed response percentage or its precision. Similarly, a list of secondary outcomes identifies the scope of planned assessment without documenting findings for those outcomes.

The safety information highlights another statistical reading issue: event counts should be interpreted with their group denominators and with clarity about event definitions. The listed serious adverse event categories and counts can be described, but they cannot support a controlled risk comparison from this design. The record also distinguishes a secondary outcome concerning events considered related to study drug from the group-level counts, whose relation to that restriction is not specified.

More broadly, the record shows the importance of complete result reporting. Without analyzed denominators, missing-data rules, multiplicity procedures, and endpoint values, readers cannot fully evaluate the precision or robustness of the findings. These omissions do not establish what the unreported analyses would have shown; they delimit what can be concluded from the registry record.

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 for statistical interpretation is that the registry record does not report the primary objective response percentage or its 90% confidence interval. Without those values, the observed result and its precision cannot be assessed. The record also does not report the number included in the primary analysis, beyond defining the intended population as participants who received at least one dose.

The study is recorded as single-group, with allocation not applicable and no masking. The three tasisulam categories are not a like-for-like control comparison, as the registry itself cautions. This record therefore does not provide a randomized comparative estimate. It also does not report whether participants were assigned to the dose categories by a specified procedure.

Missing-data handling for the primary endpoint is not reported in the registry record. The criteria for response are described, but the record does not state how unevaluable assessments, withdrawals, or incomplete follow-up affected the primary analysis. Although a censoring rule is given for duration of response, it does not fill the gap for the binary primary endpoint.

The registry lists multiple secondary outcomes but does not report their numerical results, multiplicity procedures, interim analyses, or a complete statistical analysis plan. The original sample-size justification is not reported in the registry record. Planning illustrations based on an observed effect are not the trial’s design justification and should not be read as observed power.

Finally, the safety summary does not report death counts for the listed groups, and the record does not establish whether the group-level serious adverse event counts are restricted to events considered related to study drug. These limitations constrain interpretation of both efficacy and safety information without implying what the missing results would have shown.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Tasisulam in Treating Participants With Malignant Melanoma — NCT00383292.
• Registry record last updated 2018-06-06; status last verified 2018-05.
• Results first posted 2018-06-06.
• 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

NCT00383292 is a completed phase 2, single-group study of tasisulam in unresectable or metastatic melanoma after one prior systemic treatment. The registry lists an enrollment of 130, a start date of 2006-11, and a primary completion date of 2011-09. The official title describes LY573636 as an intravenous infusion on Day 1 of a 28-day cycle.

The primary endpoint is the percentage achieving objective response, defined as complete response or partial response under RECIST v1.1, with a 90% confidence interval specified. The endpoint estimate and interval limits are not reported in the registry record. Three tasisulam dose categories are listed, but the registry cautions that they are not a like-for-like control comparison.

Secondary outcomes include survival, response and stable-disease measures, pharmacokinetics, serious adverse events, and FACT-G score. Their results, the primary analysis denominator, and several statistical-plan details are not reported in the registry record. The available information supports describing the study question and design, but not a quantitative conclusion about treatment effects.