Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer (NCT01828476), a randomized phase 2 study. The primary outcome is Biochemical Response to ABT-263 and Abiraterone and to ABT-263 in Combination With Hydroxychloroquine and Abiraterone in Patients That Are Progressing on Abiraterone.

2. Clinical Question

3. Trial Design

The registry describes a randomized, open-label, parallel phase II study. Its two planned regimens were abiraterone with ABT-263 in ARM A and abiraterone with ABT-263 plus hydroxychloroquine in ARM B. The record identifies Rutgers, The State University of New Jersey, as sponsor and Prostate Cancer as the condition.

The registry lists enrollment of 13 and a status of terminated. The start is recorded as 2013-06 and primary completion as 2016-02. The primary-outcome description states that the study was terminated early and that insufficient data were collected to assess that outcome. The registry does not report a reason for termination, so the reason should not be inferred from the outcome shortfall.

The arm-level primary result records 13.0 participants and a value of 0.0 for ARM A; ARM B has 0.0 participants and no result value. This is a very limited basis for interpreting the planned randomized comparison. In particular, the record does not establish why no ARM B participants appear in the posted outcome data, nor whether the recorded ARM A figure reflects all randomized participants, all treated participants, or a different analysis population. Those details are not reported in the registry record.

The registry lists seven secondary outcomes, including time to PSA progression, progression-free survival, measurable tumor response, circulating tumor cells, biomarker measures, and overall survival. The listed outcomes indicate a broad set of intended assessments, but they do not establish that each assessment was completed or yielded interpretable results.

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: We are reporting results on 13 eligible patients. Arm A dose escalation was completed. The study was then closed to due to slow accrual and the Investigator leaving the organization.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Study was terminated early and insufficient data was collected to assess this outcome measure.

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 Biochemical Response to ABT-263 and Abiraterone and to ABT-263 in Combination With Hydroxychloroquine and Abiraterone in Patients That Are Progressing on Abiraterone, measured over 5 years.

The primary endpoint is described as biochemical response to the study regimens, assessed by looking at PSA levels. PSA is used in prostate cancer research as a biochemical measure; change in a laboratory marker can be informative about disease activity, but it is not interchangeable with a tumor response assessment, progression-free survival, or overall survival. The registry record does not provide a response definition, a PSA threshold, or details about how measurements were converted into a response classification.

The outcome is recorded as a count of participants, with a timeframe of 5 years. A participant count can describe how many people met a prespecified response definition, but it needs a clearly defined denominator and consistent outcome ascertainment to support a meaningful comparison between arms. The registry says the study was terminated early and that insufficient data were collected to assess this endpoint. It posts a value of 0.0 for ARM A and no value for ARM B, which has no participants recorded. Therefore, the result cannot establish the frequency of biochemical response across the planned comparison. The endpoint's intended role is clear, but its operational definition and an interpretable comparative estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a randomized comparison estimate?

In general, randomization is intended to make treatment groups comparable at the point of assignment, so outcome differences can be interpreted as comparisons between assigned regimens rather than as simple differences between self-selected groups. That interpretation still depends on an adequate record of assignment, follow-up, outcome ascertainment, and analysis. The registry identifies this trial as randomized and parallel, but the primary-outcome record has no participants listed for ARM B. Thus, the posted result does not contain outcome information for both groups needed to estimate the intended comparison.

The study was unmasked. In general, lack of masking means participants or study personnel may know which regimen is being used. This can matter for outcomes involving judgment or decisions about measurement and follow-up. The primary endpoint is described as a biochemical response based on PSA levels, but the registry record does not report measurement procedures, response criteria, or safeguards related to assessment. No claim about the direction or presence of bias can be made from the masking designation alone.

How should a binary outcome be read?

In general, a binary outcome classifies each participant into one of two categories, such as meeting or not meeting a response definition. A count of participants meeting the definition needs a denominator: the number of participants whose outcomes were assessed under the applicable analysis rules. A proportion or comparative effect also depends on that denominator and on a clear description of how unavailable outcomes were treated. The record gives an ARM A count value and participant count, but it says the outcome could not be assessed adequately and gives no ARM B outcome value. The result is therefore not a usable two-arm estimate.

In general, a confidence interval describes the range of effect values compatible with the data under a specified statistical procedure. It communicates precision as well as the estimated effect. With no estimable two-arm result in the registry record, there is no comparative confidence interval to interpret. The absence of an interval does not mean that the true effect is precisely zero; it means the posted information does not support that estimate.

Why does sparse information matter?

In general, small or incomplete datasets can produce unstable estimates and wide uncertainty. If an outcome is rare, a small amount of outcome information may be especially uninformative about its frequency. If one group has no participants recorded for an endpoint, a between-group effect may not be calculable at all. These are general statistical considerations, not additional findings about this trial. The registry's explicit statement that insufficient data were collected is the key limitation for interpreting its primary endpoint.

General methods for binary outcomes may compare event risks, event odds, or model-based quantities. Choosing among them requires an analysis plan, a defined outcome, and usable data from the groups being compared. The registry record does not report a statistical plan for the primary endpoint or an analysis entry. It would therefore be inappropriate to select a method retrospectively and present its output as the trial's own analysis.

What can a recalculation or planning illustration add?

A recalculated estimate, when possible, is a simple unadjusted calculation from posted summary statistics. It is not a substitute for the sponsor's analysis, which takes precedence if a discrepancy is flagged. In this record, the values are missing or not estimable for a two-arm binary comparison, so a comparative recalculation is not available. Without an observed comparative effect, an effect-based planning illustration is also not supported.

In general, sample-size planning asks how many participants per arm might be needed under specified assumptions about the effect to detect, significance level, allocation, and statistical method. Such a calculation is a planning illustration, not evidence that a study had a particular probability of detecting an effect after it was conducted. The registry record does not report the trial's sample-size justification or its own design assumptions. No sample-size target or observed-power claim can be inferred from the enrollment record.

Why might over-dispersion matter?

Over-dispersion is a general concern for count outcomes when variation exceeds what a chosen statistical model expects. It can make standard errors too small if the model fails to allow for that extra variation. The primary endpoint is recorded as a participant count for a binary response, not as a modeled repeated count process. The registry record provides no model specification or dispersion estimate, so over-dispersion is not an identified trial finding and cannot be evaluated from the posted endpoint data.

The main methodological conclusion is therefore about estimability, not about the merits of a particular statistical model: the registry does not contain adequate primary-outcome information for the planned two-arm comparison. More elaborate methods cannot recover a comparative result when the needed outcome data and analysis details are absent.

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")
n      <- c(13)
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  ARM A  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven secondary outcomes alongside the primary biochemical-response outcome. These include time to PSA progression, progression-free survival, measurable tumor response, circulating tumor cells, biomarker assessments, and overall survival. Testing or interpreting multiple outcomes can raise a multiplicity concern: in general, the more separate questions examined, the greater the chance that some findings may appear notable by chance alone. Whether and how to address that issue depends on the prespecified analysis plan and the role assigned to each outcome.

The registry record contains no analysis entries, and a multiplicity-adjustment approach is not reported in the registry record. It is therefore not possible to determine whether the outcomes were planned as confirmatory or exploratory, whether a testing hierarchy was specified, or whether any adjustment was used. The outcome list alone does not answer those questions.

Missing-data handling is also not reported. The primary-outcome description says the study was terminated early and that insufficient data were collected. ARM B has no participants recorded for the primary result, while ARM A has a posted count. The registry does not explain the reason for the arm-level absence, the extent or pattern of missing measurements, or whether any participants were excluded from an analysis. No assumption about those matters should be treated as established.

The analysis population is not reported in the registry record. In general, an analysis may include everyone randomized, only those who started treatment, or a defined subset with evaluable outcomes; these choices can affect interpretation. The registry information does not identify which approach was used for the posted value. As a result, neither the denominator nor the handling of incomplete follow-up can be fully assessed.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypokalemia (7.7%).

For ARM A - Dose Escalation, the registry records 13 participants at risk for serious adverse events and 1 affected. It records 13 at risk and 13 affected for the other adverse-event field, and 0 deaths. These fields describe different categories and should not be conflated: the count in the other adverse-event field does not mean that all 13 participants had a serious adverse event. Hypokalemia is listed as the top serious term, with 7.7% recorded.

For ARM B - Dose Escalation, all of the adverse-event group counts are 0. That group also has 0 participants recorded at risk. These entries do not provide a safety rate for ARM B and should not be interpreted as showing an absence of adverse events in people receiving that regimen.

In general, adverse-event counts depend on the period of observation, event definitions, and the number of participants actually assessed. The registry record does not provide further details about these aspects in the registry record, nor does it describe event severity beyond the serious and other adverse-event categories. The safety entries should therefore be read as limited descriptive counts, not as a complete comparison between regimens.

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

The registry establishes that a randomized phase II study was intended to assess abiraterone and ABT-263, with or without hydroxychloroquine, in patients with metastatic castrate refractory prostate cancer progressing on abiraterone. It also establishes that the study was terminated and that the primary-outcome description identifies insufficient data to assess biochemical response. These are informative details about the conduct and reporting of the study, but they do not answer its primary comparative question.

The ARM A value of 0.0 should be interpreted in light of the stated data insufficiency. It is a posted count, not a complete estimate of the response frequency in the intended study population. ARM B has no participants recorded for this outcome, so the record cannot show whether its response experience differed from ARM A. The figures do not demonstrate equivalence, benefit, lack of benefit, or harm for either regimen.

The safety record reports one participant affected in the serious adverse-event field for ARM A, 13 affected in the other adverse-event field, and no deaths. It also lists hypokalemia at 7.7% as the top serious term. These are descriptive entries, with no corresponding assessable ARM B group in the safety record. They cannot establish a comparative safety profile.

More generally, an incomplete trial record can document the question investigators intended to study without resolving it. The listed secondary outcomes and the study rationale should not be treated as results. No medical conclusion about treatment should be drawn from the sparse posted primary outcome. The most defensible interpretation is that the registry does not provide sufficient comparative outcome data to determine how the regimens performed.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it illustrates the difference between a planned randomized comparison and an estimable comparison in the posted record. Randomization can support a rigorous comparison when outcome information is available for the assigned groups, but randomization alone cannot compensate for missing outcome data. Here, ARM B has no participants recorded for the primary outcome, and the registry explicitly says the study ended early with insufficient data to assess that outcome.

The record also shows why a zero count must be interpreted in context. A numerical zero in one arm is not automatically evidence of a true absence of responses, especially when the registry says the endpoint could not be assessed adequately and no corresponding outcome value exists for the other arm. Denominators, outcome definitions, and analysis populations are essential to reading counts correctly.

For researchers, the case emphasizes the value of transparent reporting about early termination, participant flow, endpoint definitions, missing measurements, and analysis populations. Such information helps readers distinguish a genuinely observed zero from a result that is unavailable or not estimable. It also clarifies whether a trial can support its prespecified comparison.

The record's limitations are not repaired by a more complex statistical method. Statistical modeling can address particular features of observed data, but it cannot create the missing arm-level outcome information needed for a comparative estimate. The central lesson is to separate the scientific question the study set out to address from the evidence the registry actually makes available.

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 primary limitation is explicit in the registry: early termination left insufficient data to assess biochemical response. The posted ARM A value is 0.0 with 13.0 participants recorded, but ARM B has 0.0 participants and no outcome value. The comparative primary endpoint is therefore not estimable from the posted entries.

The registry does not report why the trial was terminated, why ARM B has no participants recorded, or whether the arm-level outcome counts correspond to randomized, treated, or evaluable participants. A PSA response definition and detailed measurement procedures are also not reported in the registry record. Those omissions limit interpretation of both the endpoint and the denominator.

Although seven secondary outcomes are listed, their results are not available in the registry record for this analysis. The registry record contains no analysis entries, and it does not report the statistical plan, missing-data methods, analysis populations, multiplicity approach, or sample-size justification. These gaps prevent assessment of how the investigators intended to handle incomplete information or interpret multiple outcomes.

The safety entries are also limited: ARM B has no participants recorded at risk, so the displayed ARM A counts cannot support a comparative safety assessment. The record does not supply additional detail about duration of safety observation or event ascertainment. These limitations mean that the registry supports a description of the study and its sparse posted results, not a robust conclusion about comparative efficacy or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer — NCT01828476.
• Registry record last updated 2017-05-04; status last verified 2017-03.
• Results first posted 2017-03-31.
• 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

NCT01828476 is a randomized, unmasked, parallel phase II study sponsored by Rutgers, The State University of New Jersey. It planned to compare abiraterone with ABT-263 against abiraterone with ABT-263 and hydroxychloroquine in metastatic castrate refractory prostate cancer. The registry records enrollment of 13, a terminated status, a start of 2013-06, and primary completion of 2016-02.

The primary endpoint was biochemical response assessed through PSA levels over a stated timeframe of 5 years. The registry says early termination left insufficient data to assess it. ARM A has a posted value of 0.0 among 13.0 participants; ARM B has no participants or outcome value recorded. The two-arm result is not estimable. The record lists seven secondary outcomes and limited ARM A safety counts, but these do not resolve the primary comparison.