Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery (NCT00848016), a na phase 2 study. The primary outcome is The Proportion of Patients Who Achieve a Confirmed Objective Response to Treatment, Either Partial Response (PR) or Complete Response (CR) as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria.

2. Clinical Question

In statistical terms, this is a single-arm question about the frequency of a defined tumor response among participants who could be evaluated. It is not a direct estimate of how outcomes differ between treatment and control. Without a concurrent comparator, the response proportion cannot by itself separate a treatment effect from other explanations for observed outcomes, such as the natural course of disease or differences in who was evaluable.

The registry lists overall survival and progression-free survival as secondary outcomes. The primary endpoint is different: it focuses on whether a participant met the specified tumor-response criteria and whether that response was confirmed. The registry record does not report the primary response count or proportion, so the central numerical answer to the response question cannot be read from the posted results.

3. Trial Design

The registry describes a phase II study of R-(-)-gossypol acetic acid, an oral drug, in patients with advanced adrenocortical carcinoma. It is a single-group study with no masking and no randomized allocation. The record lists 29 enrolled participants and identifies the study as completed. Its start is recorded as 2009-02, and primary completion is recorded as 2012-03.

All participants in the treatment group were assigned the same described regimen: 20mg of oral R-(-)-gossypol acetic acid once daily on days 1-21, with cycles repeating every 28 days. The description says treatment continued in the absence of disease progression or unacceptable toxicity. The registry record does not describe a control regimen or a separate untreated group.

The primary outcome was confirmed objective response, defined as complete response or partial response under RECIST criteria, with a timeframe of up to 2 years. A response had to appear on consecutive evaluations at least 4 weeks apart to count as confirmed. Overall survival and progression-free survival are listed as secondary outcomes. Although the record lists three outcome measures, it lists no analyses.

In a single-group design, an outcome proportion describes the experience of the participants included in that analysis. It does not establish what would have happened to the same participants under another treatment. The lack of masking also means the design is not described as blinded. The record does not report whether any other steps were used to reduce assessment bias, such as independent response review.

Several operational details cannot be established from the registry description. The number of participants evaluable for the primary endpoint, the timing and number of tumor assessments, and the statistical analysis plan beyond the stated binomial estimator are not reported in the registry record. The enrollment figure should not be assumed to equal the analysis denominator: the endpoint is defined using evaluable participants, and the size of that population is not reported.

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: All 29 participants are off treatment, and all participants are evaluable for response and for adverse responses.

Overall Study

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 The Proportion of Patients Who Achieve a Confirmed Objective Response to Treatment, Either Partial Response (PR) or Complete Response (CR) as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria, measured over Up to 2 years.

The primary endpoint measures the proportion of evaluable participants who achieved a confirmed objective response: a complete response or a partial response under RECIST criteria. The registry defines a confirmed response as a response on consecutive evaluations at least 4 weeks apart. Its stated timeframe is up to 2 years.

For a complete response, the registry definition requires disappearance of all target lesions and normalization of tumor biomarkers. A partial response requires at least a 30% decrease in the sum of the longest dimension of target lesions, using the baseline sum as the reference. These definitions turn changes in tumor findings into a response category that can be counted for each evaluable participant.

As a general statistical point, a response proportion is useful because it expresses how frequently a predefined event occurred in the analyzed group. Requiring confirmation can distinguish a response meeting the criteria on repeated evaluations from one that appears on only a single evaluation. The endpoint is therefore a measure of confirmed tumor response, not a direct measure of survival, symptom change, or quality of life.

The registry says the proportion was to be estimated with the standard binomial estimator: the number of successes divided by the total number of evaluable participants. However, the registry record does not report the number of successes, the evaluable denominator, the resulting proportion, or the stated 95% confidence interval. The endpoint definition is available, but its numerical result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines the primary outcome as a percentage of participants with an event, specifically a confirmed complete or partial response. The stated estimator is the standard binomial estimator, described as the number of successes divided by the total number of evaluable participants. In this setting, a success means meeting the response definition and its confirmation requirement; an evaluable participant is included in the endpoint denominator. The registry does not report either of those counts, so the proportion cannot be reproduced from the record.

What does a confidence interval describe?

As a general statistical explanation, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used to construct it. For a response proportion, the interval would help readers assess how precisely the observed proportion estimates the underlying response frequency in a relevant population. An interval is not a guarantee that the true value lies within its limits, and it does not address every source of uncertainty. In particular, it cannot remove bias from participant selection, missing assessments, or the absence of a comparator.

The registry specifies a 95% confidence interval as the dispersion measure for the primary outcome, but does not identify the interval calculation method or report the interval itself. It is therefore not possible to assess its width or check the calculation. The standard binomial estimator is stated, but the result is missing. No alternative or adjusted response estimate is reported.

Why does the analysis denominator matter?

The numerator and denominator jointly determine a proportion. The registry’s denominator is described as the total number of evaluable participants, not necessarily everyone enrolled. Participants might be unevaluable for reasons such as missing assessment information, but whether that occurred in this trial and how it was handled are not reported in the registry record. No missing-data rule or analysis-population definition is reported. The enrollment count of 29 therefore cannot be substituted for the unknown evaluable denominator.

As a general matter, excluding participants without evaluable outcomes can change the interpretation of a proportion. The resulting estimate describes those included in the calculation, and it may not represent all enrolled participants if the ability to be evaluated is related to outcomes. Understanding that possibility requires information about participant flow, assessment availability, and analysis rules; those details are not reported in the registry record.

What does the single-group structure imply?

The study is identified as single group, with no masking and allocation listed as not applicable. There is no concurrent control group in the registry description. In a single-arm analysis, a binomial response estimate is descriptive of the analyzed group. It does not supply a randomized contrast, and it cannot by itself account for differences between treated participants and a hypothetical comparison population.

As a general statistical point, randomization helps make comparison groups similar, on average, with respect to measured and unmeasured factors. Since this record does not describe a randomized comparison, a response percentage—if reported—would not have the same interpretation as a difference between randomized groups. Unmasked assessment may also matter when outcomes require judgment, although the record does not report the response-review procedures used in this study.

How should the response criteria be understood?

The endpoint applies RECIST criteria and requires confirmation on consecutive evaluations at least 4 weeks apart. The registry defines complete response as disappearance of all target lesions and normalization of tumor biomarkers. Partial response requires at least a 30% decrease in the sum of the longest dimension of target lesions, with the baseline sum as reference. These are endpoint rules, not observed results. The record does not provide participant-level assessments or the count meeting either response category.

As a general point, a prespecified threshold makes an outcome classification more consistent by stating what change qualifies. Confirmation can reduce reliance on a single assessment. Yet the registry does not report the assessment schedule, adjudication process, or any sensitivity analyses related to response classification. Those methods cannot be inferred from the endpoint definition alone.

What can planning calculations tell readers?

As a general explanation, sample-size calculations are planning tools that describe the size of a future study under stated assumptions. They are not observed outcomes and are not evidence that a study had a particular probability of finding an effect after the fact. The registry’s planning assumptions 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. The registry record does not report the numerical planning outputs in the registry record for this analysis. These assumptions should not be mistaken for features of the actual single-group trial design or for observed power.

More broadly, the record reports no analyses, and it does not provide the statistical plan beyond the stated estimator and endpoint description. The approach used for confidence intervals, any adjustment for other analyses, and any interim-analysis procedures are not reported in the registry record. Those omissions limit independent evaluation of the analysis, separate from the more fundamental absence of the primary result.

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("Treatment (R-(-)-Gossypol Acetic Acid)")
n      <- c(29)
events <- c(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  Treatment (R-(-)-Gossypol Acetic Acid)  29  0  0.0  0.0  11.9  0.0  11.7  0.1  11.6

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies confirmed objective response as the primary outcome and lists overall survival and progression-free survival as secondary outcomes. It also lists three outcome measures, but no analyses are listed. The record does not provide a set of outcome-specific estimates or tests from which the relationship among analyses could be evaluated.

As a general statistical point, multiplicity arises when several outcomes, time points, subgroups, or hypotheses are examined. The more analyses considered, the more important it can be to explain which were primary and whether any adjustment or interpretive strategy was planned. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed statistical analysis plan. It is not possible to tell from the record whether adjustment was planned or performed.

The primary endpoint is defined among evaluable participants, but the number evaluable is not reported. The number with a confirmed response is also not reported, so neither the numerator nor denominator needed for the primary proportion is available. The handling of participants with missing or incomplete response assessments, and the definition of the analysis population, are not reported in the registry record.

The record does not describe interim analyses, stopping rules, or missing-data sensitivity analyses. These items should be treated as unreported rather than assumed absent from the conduct of the trial. Without the analysis population and missing-data rules, readers cannot determine whether the endpoint denominator followed the planned approach or how unavailable assessments were treated.

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: vomiting (10.3%), serum potassium decreased (10.3%), hemoglobin decreased (6.9%), nausea (6.9%), cardiac troponin t increased (6.9%).

The safety summary lists one treatment group, with 29 participants at risk for serious adverse events and 11 affected. It also lists 29 at risk for other adverse events and 29 affected. The summary does not report deaths. These figures should be read as event-summary counts for the treatment group, not as a comparison with a control group.

The registry lists vomiting and decreased serum potassium at 10.3% each among the leading serious adverse event terms. Decreased hemoglobin, nausea, increased cardiac troponin T, and dehydration are each listed at 6.9%. The percentages describe the entries as reported; the registry record does not supply term-specific counts in this summary.

As a general statistical point, serious adverse events and other adverse events are categories used to organize safety reporting; a participant may experience more than one event. Group-level counts do not establish that the study drug caused an event. Without a comparator, event rates cannot be contrasted with rates in another treatment group. The registry record also does not provide event timing, duration, severity details beyond the serious-event classification, or participant-level information. The summary is therefore a limited description of reported safety events, not a complete account of individual risk.

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

The record establishes that a phase II, single-group study evaluated oral R-(-)-gossypol acetic acid in advanced adrenocortical carcinoma and defined confirmed objective response as its primary endpoint. It also records the treatment schedule, the listed secondary outcomes, and selected adverse-event summaries. These registry entries describe the study’s purpose and some reported safety information.

The record does not report the response numerator, evaluable denominator, response proportion, or 95% confidence interval. It therefore does not show how many evaluable participants met the response criteria or how precisely the response frequency was estimated. The outcome definition cannot stand in for the outcome itself. The posted results also do not provide numerical results for overall survival or progression-free survival.

Even if the primary response estimate were available, its interpretation would be limited by the single-group design. An observed proportion in the treatment group would describe that group under the study’s assessment and analysis procedures. It would not be a randomized estimate of a treatment effect relative to a control. The registry lists no comparator group, and the study was unmasked.

As a general statistical principle, a confidence interval would describe sampling uncertainty in an estimate under its calculation method, but it would not resolve limitations caused by design, missing information, or assessment procedures. Here the interval itself is not reported, and the method used to calculate it is not reported. The absence of these details prevents readers from judging precision and checking the analysis.

The safety figures provide counts and listed percentages for adverse events in the treatment group. They do not establish causation, and the lack of a comparison group means they cannot show how the event experience differed from another group. The registry record does not report deaths in the safety summary.

Thus, the registry record supports a careful description of the design, endpoint, regimen, and selected safety reporting, but not a numerical conclusion about the primary response outcome. No claim about treatment benefit or lack of benefit follows from the missing response result. The distinction is between an outcome question that the study intended to address and a result that is actually reported in the registry.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry specifies a confirmed response measure, the RECIST categories used to define it, and the binomial estimator intended for the proportion. Yet it does not report the response count, evaluable denominator, estimated proportion, or confidence interval. Statistical interpretation requires both a clear estimand and the observed data used to estimate it.

The design is equally important to interpretation. A single-group study can describe outcomes among its analyzed participants, but it does not provide a randomized contrast against a concurrent control. That distinction remains important even when an endpoint is objective in wording or has a formal response threshold. The record also identifies the study as unmasked, while leaving assessment procedures unreported.

The difference between enrolled and evaluable populations is another central issue. The record lists 29 enrolled participants, while the endpoint denominator is defined as evaluable participants. Because the evaluable count and missing-assessment rules are not reported, enrollment alone cannot establish the analysis denominator. This is a practical reminder that a reported enrollment total does not automatically tell readers how many participants contributed to each endpoint.

Finally, safety summaries should be interpreted with attention to their scope. Counts of participants affected and listed event percentages describe reports in the treatment group, not comparative risks or causal effects. The registry’s limited safety summary can be informative while still leaving important details—such as timing, participant-level patterns, and a control-group comparison—not reported.

Statistically, the record matters as an example of how design, analysis population, endpoint definition, and result availability jointly shape what can be concluded. Clear criteria help define what would count as response, but missing numerical results and limited comparative structure constrain inference. Those limits are part of the evidence description, not an invitation to fill gaps with assumptions.

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 main limitation for interpreting the primary outcome is that its numerical result is not reported in the registry record. The response count, evaluable denominator, proportion, and 95% confidence interval are unavailable. Although 29 participants were enrolled, the endpoint is defined among evaluable participants, and the record does not state how many were evaluable.

The study has a single-group design and no masking. Allocation is listed as not applicable, and no control group is described. Consequently, the registry record does not provide a randomized comparison. Any outcome proportion, if reported, would describe the analyzed treatment group rather than a between-group difference.

The response definition is detailed, including confirmation on consecutive evaluations at least 4 weeks apart and specified criteria for complete and partial response. However, the registry does not report the assessment schedule, response-review procedures, or handling of missing or unevaluable assessments. The statistical method for constructing the stated confidence interval is also not reported.

The record lists overall survival and progression-free survival as secondary outcomes but provides no numerical results for them in the information. It does not report their definitions, event counts, estimates, or uncertainty measures. The statistical plan, multiplicity approach, analysis-population rules, interim analyses, and missing-data sensitivity analyses are not reported in the registry record.

The safety summary is limited to group-level counts and selected serious-event terms and percentages. Deaths are not reported in that summary, and the record does not provide event timing or participant-level detail. Without a comparator, the safety figures cannot show comparative event frequencies. These limitations apply to interpretation of the registry record and should not be mistaken for proof that unreported procedures or data did not exist.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery — NCT00848016.
• Registry record last updated 2014-05-07; status last verified 2014-01.
• Results first posted 2014-02-21.
• 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

NCT00848016 is a completed phase II, single-group study of oral R-(-)-gossypol acetic acid in advanced adrenocortical carcinoma. The registry lists 29 enrolled participants. The treatment description specifies 20mg once daily on days 1-21, with treatment repeating every 28 days in the absence of disease progression or unacceptable toxicity.

The primary endpoint was the proportion of evaluable participants with a confirmed complete or partial response under RECIST criteria, with confirmation on consecutive evaluations at least 4 weeks apart and a timeframe of up to 2 years. Overall survival and progression-free survival are listed as secondary outcomes. No analyses are listed, and the primary response estimate and 95% confidence interval are not reported in the registry record.

The safety summary reports 11 participants affected by serious adverse events and 29 affected by other adverse events in the treatment group. It lists vomiting and decreased serum potassium at 10.3% each among serious event terms. The single-group design does not provide a randomized comparator for interpreting efficacy or safety differences.