Extension Trial of Deforolimus (Ridaforolimus, MK-8669) in Participants With Advanced Cancer (MK-8669-038): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Trial of Deforolimus (Ridaforolimus, MK-8669) in Participants With Advanced Cancer (MK-8669-038) (NCT00836927), a non-randomized phase 2 study. The primary outcome is Number of Participants Who Experienced an Adverse Event.

2. Clinical Question

This is a descriptive safety question in a population selected through prior participation and clinical history, not a test of whether ridaforolimus improves outcomes relative to another treatment. Progression-free survival, overall survival, and duration of response are listed as secondary outcomes, but their statistical analyses are not reported in the registry record. The available results therefore address adverse-event counts rather than comparative effectiveness or the course of cancer outcomes.

3. Trial Design

The registry identifies this as a Phase 2, non-randomized, unmasked, single-group extension trial of deforolimus, also called ridaforolimus or MK-8669. It enrolled 7 participants with advanced cancers. The study is marked terminated. Its recorded start date is 2009-02-01, and its primary completion date is 2017-04-03.

The extension was intended to describe long-term safety among participants for whom clinical benefit had been established in a parent trial, or who remained in long-term follow-up. The registry names parent studies MK-8669-013, NCT00060645; MK-8669-016, NCT00112372; and MK-8669-028, NCT00704054. That context matters: participants entering an extension study are not necessarily representative of all people with advanced cancer or of everyone who began treatment in a parent study.

Actual-treatment groups cover oral ridaforolimus schedules of 10 mg on Days 1-5, 10 mg on Days 1-6, 20 mg on Days 1-5, 30 mg on Days 1-5, and 40 mg on Days 1-5. Participants could continue intravenous ridaforolimus from the parent trial at the same dose before switching to oral tablets. The posted adverse-event groups distinguish observations through the data cut-off from entries marked post data cut-off. These categories should be read as registry reporting groups, not as randomized assignments.

Because treatment allocation was non-randomized and there is no control group, differences among dose groups cannot be interpreted as unbiased treatment contrasts. Dose, prior treatment history, eligibility, follow-up time, and the reasons for entering or continuing in the extension may differ across participants. Details about allocation procedures, dose changes, and the full protocol are not reported in the registry record. The record also does not report a statistical analysis plan or inferential analyses.

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: Participants may have continued ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received any study drug on this extension protocol according to their actual treatment.

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 Number of Participants Who Experienced an Adverse Event, measured over Up to approximately 2991 days, including 30 days after the last dose (through data cut-off date of 03 Apr 2017).

The primary endpoint is the number of participants who experienced an adverse event. The registry defines an adverse event broadly as an unintended or undesirable, noxious, or pathological change compared with pre-existing conditions, whether or not it was considered related to study drug. The result is a participant count, not an event rate, severity score, or causal estimate.

This endpoint is used to describe safety during prolonged exposure and follow-up. Counting participants affected gives a direct summary of how many people had at least one event under the registry definition. It does not convey how many separate events each participant experienced, how long events lasted, or whether a participant experienced multiple events. Those details are not reported in the primary endpoint description.

The stated timeframe is up to approximately 2991 days, including 30 days after the last dose, through the data cut-off date of 03 Apr 2017. The primary population is all participants who received any study drug on the extension protocol, classified by actual treatment. Consequently, the outcome is descriptive of exposed participants in this extension, rather than an estimate of risk relative to an untreated or alternative-treatment group.

General statistical context: counts are straightforward to interpret, but their precision depends on how many participants contribute information and on the completeness and duration of observation. A count alone cannot distinguish a common but mild event from a rare but serious event. Seriousness, event type, timing, and treatment relationship require separate information; not all of these details are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, non-randomized extension trial and reports participant counts for adverse events by actual treatment. It lists no statistical analyses. That means the results should be read as descriptive safety data, not as outputs from a formal comparative model. The record does not report methods for hypothesis testing, adjustment, confidence-interval construction, or handling repeated events.

What does a participant count represent?

The primary endpoint counts participants who experienced an adverse event, rather than counting every event episode. A participant with multiple events may still contribute only once to a count of participants affected, depending on the outcome definition. The registry states that the number of participants experiencing an event is presented. It does not provide event-level detail in the primary endpoint definition, so the count should not be interpreted as a tally of all episodes, their duration, or their severity.

The definition includes events regardless of their assessed relationship to study drug. This is useful for broad safety description because it does not exclude events based on a causal judgment. It also means that an event count, by itself, does not establish that the drug caused the event. Determining causality would require additional clinical assessment and information not reported in the primary outcome.

Why does the study design matter?

In a randomized study, random allocation can support a fairer comparison between treatment groups, subject to other design and analysis conditions. This extension is non-randomized and has no like-for-like control group. Its actual-treatment groups are therefore not designed to estimate a causal contrast. Participants may differ in prior treatment, clinical history, dose, duration of exposure, or follow-up. Differences in event counts across these groups could reflect such differences rather than an effect of the dose schedule.

General statistical context: a comparison of proportions is most informative when groups are defined clearly, have comparable observation, and are large enough for uncertainty to be assessed. For a small group, a change in the experience of one participant can substantially alter the apparent pattern. The posted counts should therefore be understood as the experiences recorded in these participants, not stable estimates for a wider population.

How should observation time be considered?

The primary endpoint timeframe extends up to approximately 2991 days and includes 30 days after the last dose, through the data cut-off date of 03 Apr 2017. A maximum or stated study timeframe does not mean every participant was observed for that entire period. The registry does not report participant-specific follow-up durations or exposure time in the primary result. Without those details, raw counts cannot account for different opportunities to experience or record an event.

General statistical context: when participants have different lengths of observation, time-to-event methods or rates based on person-time may sometimes address that difference. These approaches require appropriate event and follow-up data and a specified analysis. The registry lists progression-free survival, overall survival, and duration of response as secondary outcomes, but it reports no analyses for them. It is not appropriate to assume that any particular time-to-event method was used.

What does the planning description mean?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The described effect to detect is a stated fraction of the observed effect. These assumptions are not the trial’s own design: the trial is non-randomized and single-group, and the posted results contain no analyses. Any sample-size illustration should be read as planning information, not as observed power or evidence that the study had a particular ability to detect a difference.

General statistical context: power is a design-stage probability tied to a particular assumed effect, outcome variability, allocation, and analysis. It is not a measure of whether the observed result is true, and it does not repair limitations in study design. The registry does not report the trial’s sample-size justification or a protocol-based power calculation. The assumptions described for planning should not be substituted for a missing trial-specific statistical plan.

What can be inferred from the absence of analyses?

The registry reports zero statistical analyses. This does not mean that no events occurred; event counts are listed. It means that no inferential analysis is available to quantify uncertainty or to test a comparison. No adjusted model, treatment-effect estimate, p-value, or confidence interval is reported. No method for addressing multiple comparisons, missing observations, or changing follow-up is reported either.

In general, statistical methods should match the question and data structure. A binary outcome such as whether a participant experienced an event can be summarized by counts and, with appropriate assumptions, proportions and uncertainty intervals. Repeated events, differing exposure durations, or time-to-event outcomes call for other definitions and methods. Those general options do not establish what was done in this trial; the registry record does not report such 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("Ridaforolimus 10 mg Days 1-5", "Ridaforolimus 10 mg Days 1-6", "Ridaforolimus 20 mg Days 1-5", "Ridaforolimus 30 mg Days 1-5", "Ridaforolimus 40 mg Days 1-5")
n      <- c(3, 1, 1, 1, 1)
events <- c(3, 1, 1, 1, 1)
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  Ridaforolimus 10 mg Days 1-5  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Ridaforolimus 10 mg Days 1-6  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Ridaforolimus 20 mg Days 1-5  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Ridaforolimus 30 mg Days 1-5  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Ridaforolimus 40 mg Days 1-5  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

Several outcomes are named: the primary adverse-event count and the secondary outcomes progression-free survival, overall survival, and duration of response. The registry reports zero statistical analyses. It does not report whether the outcomes were tested, whether any were designated for confirmatory inference, or how multiplicity across outcomes or comparisons was handled. No correction method or hierarchy for interpreting multiple tests is reported in the registry record.

Missing-data methods are also not reported. The primary population is defined as all participants who received any study drug on the extension protocol, according to actual treatment. The record does not explain how participants with incomplete follow-up, missing outcome information, or changes in treatment were handled in the reported counts. It does not state whether any imputation or sensitivity analysis was conducted.

General statistical context: missing outcomes can affect interpretation when the reason information is unavailable is related to health status, exposure, or the chance of an event. The direction and size of any resulting bias depend on circumstances that cannot be determined from counts alone. No assumptions about missingness should be attributed to this study.

The registry’s primary population definition should not be confused with a complete account of analysis populations. The record does not report separate safety, intention-to-treat, or per-protocol analysis sets, nor does it provide participant flow or reasons for discontinuation. As a result, it is not possible to determine from the reported material how every enrolled participant relates to every outcome count.

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: gastrointestinal haemorrhage (100.0%).

The serious adverse-event figures are participant counts by actual-treatment group. Through the data cut-off, the 10 mg Days 1-5 group lists 3 at risk and 0 affected; the 10 mg Days 1-6 group lists 1 at risk and 1 affected; the 20 mg Days 1-5, 30 mg Days 1-5, and 40 mg Days 1-5 groups each list 1 at risk and 0 affected. These small group counts are descriptive and should not be treated as stable estimates of risk or as comparative evidence between dose schedules.

Gastrointestinal haemorrhage is listed among the leading serious-event terms at 100.0%. The denominator and the exact counting context for that percentage are not reported in the registry record, so it should not be translated into a participant count or treated as a population-level rate. The data also list deaths by treatment group, but the registry information does not establish their cause or relationship to study drug.

General statistical context: serious events are distinct from the broader primary adverse-event endpoint, which includes any qualifying event regardless of relationship to study drug. Seriousness, event type, and attribution answer different questions. The counts do not establish causation, and the non-randomized design offers no control group against which to compare background event experience.

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

The results mean that the registry records adverse-event experience among participants who received ridaforolimus in this extension, grouped by actual treatment. The primary endpoint is broad: it counts participants with an adverse event regardless of whether the event was considered related to study drug. Serious and other adverse-event counts are presented separately in the posted results, and the serious-event term gastrointestinal haemorrhage is listed at 100.0%.

The results do not establish that ridaforolimus caused any particular event. Nor do they show that one dose schedule is safer than another. The study was non-randomized, had no control group, and included very few participants in each listed treatment group. Participants could also continue intravenous treatment from a parent trial before switching to oral tablets. Differences in prior history, exposure, and follow-up may affect the counts.

The results also do not answer whether ridaforolimus affected cancer outcomes. Progression-free survival, overall survival, and duration of response are listed as secondary outcomes, but their analyses and results are not reported in the registry record. No statistical tests or uncertainty intervals are reported for the adverse-event counts.

General statistical context: descriptive findings can document what was observed in a study population without estimating what would happen under a different treatment or in a broader population. A causal treatment comparison requires a suitable design and analysis, and estimates of precision require appropriate methods and data. Neither can be recovered from a small set of counts alone.

The extension’s stated purpose was long-term safety description in participants with prior clinical benefit in parent trials or continued long-term follow-up. That selected context defines the scope of interpretation. The results should not be generalized automatically to all people with advanced cancer, to people without prior treatment benefit, or to treatment settings that differ from the extension protocol.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction in biostatistics: a registry can report clinically relevant safety counts without providing a comparative treatment-effect analysis. Counts of participants with adverse events are meaningful descriptions of the recorded experience, but they do not by themselves identify a causal effect, quantify uncertainty, or establish how the results compare with another treatment.

The extension setting is also statistically important. Participants entered from parent studies after clinical benefit had been established or while remaining in long-term follow-up. This selection differs from enrolling an unselected population at the start of treatment. The extension therefore addresses a specific safety-description question in a specific group, and the findings have limited reach beyond that context.

The non-randomized, single-group design and very small actual-treatment groups make dose-group contrasts especially difficult to interpret. General statistical context: randomization helps balance measured and unmeasured baseline factors on average, whereas non-randomized groups may differ for reasons related to treatment selection. Sparse counts also leave substantial uncertainty about the frequency of uncommon events. The registry reports no inferential analyses to quantify that uncertainty.

The record is useful for understanding what was registered as the primary endpoint, how the extension population was defined, which dose schedules were listed, and what adverse-event counts were posted. It also shows why outcome names and numerical analyses should not be conflated: secondary outcomes are listed, but their results are not reported. Careful statistical reading preserves that distinction rather than turning descriptive observations into claims the design and data cannot support.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry marks the study terminated and reports enrollment of 7. The small number of participants limits the descriptive scope of the safety findings, particularly within the separate actual-treatment groups. The record does not report a control group, random allocation, or blinding. Consequently, neither comparisons between schedules nor comparisons with another treatment can be interpreted as randomized treatment effects.

Participants came from an extension context tied to prior parent trials and long-term follow-up. Their selection may limit generalizability. The registry does not report enough participant-level information to assess how prior treatment, clinical history, duration of exposure, or follow-up differed across the listed groups. It also does not provide participant-specific observation times, so counts cannot be standardized for differing opportunity to experience an event.

The posted results include entries through and post data cut-off, but the registry does not explain the relationship between those entries in enough detail to reconstruct an analysis population or follow-up history. The denominator for the 100.0% serious-event term is not reported. The record also does not report details such as event-level timing, duration, or the full assessment of relationship to study drug.

Although secondary outcomes are listed, their statistical results are not reported. No inferential analyses, uncertainty intervals, sample-size justification, multiplicity approach, missing-data method, or complete statistical plan are reported in the registry record. These omissions constrain interpretation; they should not be filled with assumptions about what the protocol may have specified.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Extension Trial of Deforolimus (Ridaforolimus, MK-8669) in Participants With Advanced Cancer (MK-8669-038) — NCT00836927.
• Registry record last updated 2019-02-18; status last verified 2019-02.
• Results first posted 2018-05-03.
• 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

NCT00836927 is a Phase 2, non-randomized, unmasked, single-group extension trial of ridaforolimus in participants with advanced cancer. Registry enrollment was 7. The study aimed to describe long-term safety among participants with established clinical benefit in parent trials or those remaining in long-term follow-up. It is marked terminated, with a start date of 2009-02-01 and primary completion date of 2017-04-03.

The primary endpoint is the number of participants experiencing an adverse event, regardless of relationship to study drug, through a timeframe extending up to approximately 2991 days and including 30 days after the last dose. The registry lists actual-treatment dose groups and serious and other adverse-event counts. Progression-free survival, overall survival, and duration of response are listed as secondary outcomes, but their analyses are not reported. The registry reports no statistical analyses, and its record does not provide a control-group comparison, inferential estimates, or a statistical plan.