Everolimus for Cancer With TSC1 or TSC2 Mutation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus for Cancer With TSC1 or TSC2 Mutation (NCT02201212), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The clinical rationale in the registry record is that everolimus may block mTOR, a factor involved in cell growth, and that prior responses had been observed in some patients whose cancers had TSC1 or TSC2 mutations. That rationale motivates the study question; it is not itself evidence of an outcome in this trial.

The study was registered as NCT02201212 and sponsored by Dana-Farber Cancer Institute. Its official title describes a Phase II trial of everolimus for cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. The registry lists a planned enrollment of 30. The central statistical question is whether the posted results quantify responses in this single treated group. They do not: no primary response count, response estimate, confidence interval, or analysis result is reported in the registry record.

3. Trial Design

This was a Phase II, single-group study with an enrollment of 30. The registry lists allocation as NA and masking as none. No separate control group is described, so the design does not estimate a randomized difference between everolimus and another treatment or no treatment. The trial status is completed. The listed start is 2014-09, and primary completion is listed as 2019-06.

Participants received everolimus as a drug intervention. The regimen is described as a fixed oral dose once a day per 28 day cycle. Participants could stay on study while they did not progress, up to a maximum of 24 months. Tumor assessments were planned after every 2 cycles for as long as participants remained on study. The primary endpoint timeframe is recorded as baseline, every 8 weeks, and 2 years.

These design details describe how treatment and assessment were organized, but do not establish how many participants completed treatment, how many had scans, or how long individuals remained under observation. Those details are not reported in the registry record. Nor does the record describe dose amount, dose modifications, treatment discontinuation rules beyond progression and the maximum duration, or the handling of missed assessments.

Duration of response, progression-free survival, overall survival, and toxicity rate are listed as secondary outcomes. The record identifies 5 outcome measures, but does not provide analysis results for them. A completed status indicates that the study record is marked completed; it does not supply the missing endpoint estimates or establish what the observed response experience was.

Because the study has no concurrent comparison group, any response count would describe outcomes among participants treated in this study. It could not, on its own, distinguish treatment effects from disease course, participant selection, assessment practices, or other influences. The registry record does not report a protocol-based comparison with an external or historical group.

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.

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 Objective Response Rate, measured over Baseline, Every 8 weeks, 2 Years.

The primary endpoint is Objective Response Rate, with the unit recorded as participants. It is based on RECIST 1.1 criteria for target lesions assessed by scan. Complete response means disappearance of all target lesions. Partial response means at least a 30% decrease in the sum of the longest diameters of target lesions. Overall response combines complete and partial responses.

Objective response is used in oncology trials to describe measurable tumor change under a defined assessment framework. Using specified criteria gives the response classification a consistent basis across scans and participants. The recorded assessment schedule—baseline, every 8 weeks, and 2 years—sets the timeframe for evaluating that endpoint in this study.

The registry record does not report the number of complete responses, partial responses, or participants with an overall response. It also does not report a response-rate estimate, confidence interval, or analysis method for this endpoint. Consequently, the endpoint definition can be described, but the trial's observed response result cannot be interpreted from the registry record. The stated criteria explain how responses were to be classified; they do not tell readers how many participants met those criteria.

General: a response rate is a proportion based on the number of participants meeting a response definition relative to an eligible analysis population. Its interpretation depends on the response criteria, assessment schedule, analysis population, and handling of participants without evaluable follow-up. The registry record does not report those analysis details or the result needed to quantify response in this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a binary primary outcome in terms of participants with an event, specifically participants meeting the objective response definition. It does not report an analysis result, a statistical model, or a confidence interval. The following concepts are general explanations of methods relevant to this type of endpoint; they are not claims about analyses performed in this trial.

What does a binary endpoint represent?

General: a binary endpoint classifies each participant into one of two outcome categories, such as meeting or not meeting a response criterion during a defined assessment period. A response count is the number who meet the criterion. To estimate a response rate, the count must be related to a clearly defined analysis denominator. The registry record does not report the count or denominator used for an objective response analysis.

A response classification also depends on the operational definition and evaluation schedule. In this study, the record specifies RECIST 1.1 and identifies complete response, partial response, and overall response. It says tumor assessments were to occur after every 2 cycles and gives a primary endpoint timeframe of baseline, every 8 weeks, and 2 years. It does not report how scans were reviewed, whether assessment was independent or investigator-based, or how a participant with no post-baseline scan was classified.

Why is uncertainty important?

General: a point estimate alone does not show how much uncertainty is associated with an observed result. A confidence interval gives a range of values that are compatible with the data under a specified statistical method and its assumptions. Its width is affected by the amount of information in the data and by the method used. Because no response result or interval is reported, the precision of the primary endpoint cannot be evaluated for this study.

General: a hypothesis test evaluates data against a specified null hypothesis under a statistical model. A p-value is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. The registry record reports no analysis results or hypothesis test for the primary endpoint, so no such conclusion can be drawn from the posted information.

What does a single-group design permit?

General: a single-group analysis can describe outcomes in the participants who received the study intervention. It does not, without an appropriate comparison design and assumptions, isolate the intervention's effect from other factors that could influence outcomes. Randomized allocation can support a more direct between-group comparison by helping balance measured and unmeasured factors on average. This study is not listed as randomized and has no comparator arm.

The absence of a comparator also means that a response count should not be interpreted as a treatment-versus-control contrast. Even if a response estimate were available, it would be a description of this study group under its eligibility, treatment, and assessment conditions. The registry record does not describe an external-control analysis or a prespecified benchmark comparison.

How should planning illustrations be read?

General: sample-size calculations are planning tools. They describe how many participants or events a hypothetical design might require under stated assumptions; they are not observed results and do not establish the power achieved by a completed study. The planning assumptions described for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. For time-to-event illustrations, the stated convention is a total event count; other illustrations refer to participants per arm.

These assumptions do not describe the registered study design, which is single group and does not list a comparator arm. The illustrations are therefore not the trial's own design justification, nor evidence of its actual precision. The registry record does not report the trial's sample-size justification. It also does not report a numerical observed effect from which a planning illustration could be interpreted in this record.

Why do analysis details matter?

General: a sound interpretation requires knowing which participants were included, how missing assessments were handled, which endpoint definition was applied, and what uncertainty method was used. For a scan-based response endpoint, missing or unevaluable assessments can affect both the denominator and classification. Different choices can lead to different estimates. The registry record does not state the analysis population, missing-data approach, or statistical method for objective response.

These gaps do not imply that a particular method was or was not used outside the registry entry. They mean only that the relevant information is not reported in the registry record. With no analysis result and no stated inferential method, the available record supports description of the planned endpoint and design, but not independent reconstruction or evaluation of an efficacy analysis.

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("Everolimus")
n      <- c(30)
events <- c(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  Everolimus  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 objective response rate as the primary outcome and lists duration of response, progression-free survival, overall survival, and toxicity rate as secondary outcomes. It does not report a statistical testing hierarchy, a multiplicity adjustment, or whether any outcomes were designated as exploratory. The approach to multiple outcome comparisons is not reported in the registry record.

General: when several outcomes or hypotheses are examined, the chance of at least one apparently unusual result can increase if tests are interpreted without accounting for the number of comparisons. A prespecified hierarchy or adjustment can help define how evidence across outcomes should be interpreted. This is a general statistical issue, not a claim that a particular procedure was used or needed in this trial.

The record does not report missing-data methods, the number of participants with missing or unevaluable scans, or an analysis population for the primary endpoint. It also does not describe whether participants who discontinued treatment or progressed before an assessment were counted as nonresponders, excluded, or handled in another way. These details are important for interpreting a scan-based endpoint and its denominator.

No statistical analysis results are recorded. The registry record does not state an intention-to-treat population, a per-protocol population, or another analysis set. It does not report imputation, sensitivity analyses, interim analyses, or a statistical analysis plan. Their use or absence cannot be inferred from the information recorded.

General: missing-data assumptions matter because participants without observed outcomes may differ from those with complete follow-up. Analyses that assume different outcomes for missing participants can yield different interpretations. Without the number and handling of missing assessments, the robustness of an objective response estimate cannot be assessed. In this case, the estimate itself is not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonitis (6.7%), anemia (3.3%).

The safety record lists 30 participants at risk for serious adverse events and 3 participants affected. It also lists 30 at risk for other adverse events and 20 affected. These are participant counts, not event totals: one participant may experience more than one event, and the record does not provide event-level detail.

The top listed serious adverse event terms are pneumonitis at 6.7% and anemia at 3.3%. The registry record does not specify whether these terms represent distinct participants, whether the list is exhaustive, or the severity grade beyond identifying them as serious adverse events. The percentages should be read as recorded, rather than as a basis for reconstructing additional counts.

One death is recorded. The registry record does not report the cause of death or whether it was considered related to everolimus. It also does not provide timing, duration, or treatment attribution for the serious or other adverse events. These safety figures are descriptive; without a comparator they do not establish how event rates differ from another treatment or from the expected course of disease.

General: serious adverse events are a regulatory category and should not be treated as synonymous with all adverse events or with events caused by the study drug. Attribution requires information about the investigator's assessment and event context, which is not reported in the registry record.

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

The record establishes that a Phase II, single-group study evaluated everolimus in cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. It describes the oral daily regimen, the maximum time on study, the tumor assessment schedule, and a RECIST 1.1 objective response endpoint. It also reports participant counts for serious and other adverse events and lists serious event terms.

It does not report the primary objective response result. No response count, rate, confidence interval, or statistical analysis is recorded. Accordingly, the registered information does not establish the observed frequency of tumor response in this study or the precision of any response estimate. The secondary outcome names likewise do not provide their results.

The single-group design is important to interpretation. It can describe outcomes among participants who received everolimus, but it does not provide a randomized comparison with a control group. Even a reported response in this cohort would not by itself establish the size of a causal treatment effect. The registry record does not provide an external comparator or comparative analysis.

The safety counts should also be interpreted descriptively. They identify numbers of participants recorded as affected, and selected serious event terms, but do not explain event attribution or provide a comparison group. The recorded death count has no reported cause or treatment relationship in the registry record.

General: statistical results answer questions only to the extent that the endpoint, analysis population, missing-data handling, and uncertainty are clearly reported. Without the primary result and analysis details, neither a strong nor a weak efficacy conclusion is justified from this registry entry. The absence of a posted result is a limitation of the information available in the registry record, not evidence that no outcomes were collected or analyzed elsewhere.

The most defensible interpretation is therefore about the design and reporting: this was a completed, molecularly selected, single-group Phase II study with a defined response endpoint, but its primary response findings are not reported in the registry record.

14. Why This Trial Matters Statistically

This study addresses a question organized around molecular features rather than a single cancer diagnosis: it enrolled cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. That makes the population definition central to interpreting any outcome. The registry record states the molecular eligibility concept, but does not give the distribution of mutation types, cancer types, or baseline characteristics needed to describe the enrolled group in greater detail.

Statistically, the study illustrates why a defined endpoint and a reported result must be considered together. RECIST 1.1 supplies explicit response categories, and the registry describes a recurring tumor assessment schedule. Those details help readers understand what was intended to count as a response. They cannot replace the response count, denominator, estimate, or uncertainty interval, none of which is reported in the registry record.

The single-group design is also central. A one-arm study can characterize outcomes in a selected cohort, but it cannot provide a randomized treatment contrast. The design and the outcome reporting therefore constrain the claims that can be made, even before considering the absence of a posted efficacy result.

The record also shows why safety counts need context. Participant counts and serious event terms are useful descriptive information, but they do not indicate causality or comparative risk without attribution details and a suitable comparison. The registry does not report those details.

The statistical importance of this trial, as represented in the registry, lies in these interpretive boundaries: biomarker-defined eligibility, a scan-based binary endpoint, a single-group design, and incomplete outcome reporting. Clear reporting of analysis populations, endpoint estimates, uncertainty, missingness, and safety attribution would be needed to assess the study's observed findings more fully. Those items are not reported in 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 main limitation for interpreting efficacy is that the registry record does not report the primary objective response result. It provides neither the response count nor an estimate and uncertainty interval. Although the record identifies a primary endpoint and an assessment timeframe, it does not state the number of participants evaluable for that endpoint or how missing and unevaluable scans were handled.

The study is single group, with no comparator arm. This limits the ability to distinguish outcomes associated with treatment from other influences. The record also lists no masking. It does not describe scan review procedures or whether response assessment was independent, so the assessment process cannot be characterized further.

The enrolled population is defined by cancer and mutation criteria, but the record does not report the cancer-type or mutation-type distribution, baseline characteristics, or participant-level outcome detail. It is therefore not possible to assess how broadly the enrolled group represents the molecularly defined population of interest or whether outcomes differed across subgroups.

Details needed to evaluate the analysis are not reported in the registry record, including the statistical analysis plan, analysis population, missing-data method, multiplicity approach, and sample-size justification. The planning assumptions described for sample-size illustrations are not the trial's own design justification and do not substitute for a reported analysis.

Safety interpretation is also limited. The record gives affected-participant counts and selected serious adverse event terms, but not timing, treatment attribution, event-level detail, or cause of death. The secondary outcomes are listed without analysis results. Together, these reporting gaps prevent a fuller assessment of efficacy, precision, comparative safety, and the consistency of findings across outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Everolimus for Cancer With TSC1 or TSC2 Mutation — NCT02201212.
• Registry record last updated 2020-09-16; status last verified 2020-09.
• Results first posted 2020-09-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT02201212 is a completed Phase II, single-group study sponsored by Dana-Farber Cancer Institute. It enrolled 30 cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. The record lists everolimus as the intervention, given orally once a day per 28 day cycle, with treatment up to a maximum of 24 months while participants did not progress.

The primary endpoint is objective response rate assessed by RECIST 1.1, with tumor assessments described after every 2 cycles. Duration of response, progression-free survival, overall survival, and toxicity rate are listed as secondary outcomes. The registry record does not report the primary response count or statistical analysis results.

Safety entries list 3 participants affected by serious adverse events, 20 affected by other adverse events, and 1 death. Pneumonitis and anemia are the top listed serious adverse event terms. Event attribution and cause of death are not reported in the registry record.