Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial (NCT04284774), a na phase 2 study. The primary outcome is Objective Response Rate (Complete Response + Partial Response) in Pediatric Patients Treated With Tipifarnib.

2. Clinical Question

This is a molecularly selected treatment study within Pediatric MATCH: eligibility centers on an HRAS genomic alteration across multiple diagnoses, rather than on one tumor type alone. The clinical question is whether patients in this selected population have an objective response while receiving the listed regimen. Objective response focuses on tumor shrinkage meeting the specified response categories; it does not by itself summarize all aspects of disease control, duration of response, survival, or treatment burden.

The record also lists progression-free survival and the percentage of patients experiencing grade 3 or higher adverse events as secondary outcomes. Those outcomes address different questions from objective response: progression-free survival concerns time until progression or death, while the adverse-event outcome concerns safety. Results for these outcomes are not reported in the registry record. The posted information therefore describes the intended questions, but does not establish their answers.

3. Trial Design

This is a phase II, single-group, open-label treatment study sponsored by the National Cancer Institute. The registry lists allocation as NA and masking as none. Participants receive tipifarnib; there is no control group against which to compare outcomes. The trial is part of NCI-COG Pediatric MATCH, a treatment subprotocol for patients whose tumors harbor HRAS genomic alterations.

The eligible disease categories span advanced solid tumors, lymphoma, and histiocytic disorders. The condition list includes recurrent and refractory forms of multiple tumor types. Thus, the study population is defined by both the molecular alteration and the listed disease eligibility, while containing a range of diagnoses. The registry reports an enrollment of 5. It does not report the number enrolled within each diagnosis or provide a breakdown of participant characteristics.

The intervention is tipifarnib administered orally as tablets or through a nasogastric or gastric tube. The listed dose is 350 mg/m^2/dose twice daily, with a maximum of 600 mg/dose twice daily, with food on days 1-7 and 15-21. The schedule repeats every 28 days for up to 26 cycles (2 years), provided disease progression or unacceptable toxicity does not occur. The record does not report how many participants started treatment, completed treatment, or stopped early.

The primary outcome is objective response rate, defined as the percentage of evaluable patients whose best response is complete response or partial response. Response is assessed through up to 2 years from study entry. The registry describes use of revised RECIST version 1.1, with specific criteria for different tumor subtypes, including 2-dimensional measurements for CNS tumors. The endpoint description specifies a Wilson score confidence interval with a 90% confidence level.

The study status is active, not recruiting. Its start date is 2020-10-13, and its primary completion date is 2024-03-31. These registry entries do not establish that outcome data have been posted or that follow-up is complete for every participant. No randomized comparison, masking, or independent control is described.

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: Between 10Oct2020 and 31Mar2024, 7 subjects matched and 5 were included and treated with study drug. Subjects received a median of 2 cycles of study drug (range 1-4 cycles).

Overall Study

Reasons for not completing this period:

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 (Complete Response + Partial Response) in Pediatric Patients Treated With Tipifarnib, measured over Up to 2 years from study entry.

The primary endpoint is objective response rate: the percentage of evaluable patients whose best response on study is complete response or partial response. It is assessed through up to 2 years from study entry. The response criteria are based on the revised RECIST guideline, version 1.1, with specific criteria for tumor subtypes; the description notes 2-dimensional measurements for CNS tumors.

Objective response is used to capture tumor shrinkage that reaches a prespecified response category. Combining complete and partial responses into a response rate gives a proportion of evaluable participants meeting either category. It is a binary outcome at the participant level: each evaluable participant is classified according to whether the best response meets the responder definition. This makes the endpoint interpretable as a proportion, while the underlying assessment depends on the response criteria and evaluability rules.

The registry says response rates will be calculated among evaluable patients and that confidence intervals will use the Wilson score method. The enrolled population and the evaluable population need not be identical; however, the criteria for evaluability and the actual number evaluable are not reported in the registry record. Nor are response counts, the observed response rate, or its confidence interval reported. Consequently, the endpoint definition is available, but its result cannot be assessed from the posted information.

Objective response does not alone describe how long a response lasts or how long participants remain free from progression. Those are distinct questions, and progression-free survival is listed separately as a secondary outcome. Safety is also assessed separately through adverse-event outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response rate estimate?

Objective response rate is a proportion: the number of evaluable participants meeting the responder definition relative to the evaluable population. The registry defines a responder as a patient whose best response is complete response or partial response. “Best response” means the response category achieved during the specified assessment period, rather than a single measurement taken without regard to the rest of the follow-up. The stated timeframe is up to 2 years from study entry.

The endpoint is not a time-to-event measure. It classifies participants by whether they meet the response definition; it does not, by itself, capture the time until response, the duration of a response, or the time until progression. Progression-free survival is a separate secondary outcome in the registry record. These outcomes answer related but different clinical and statistical questions.

Why use a confidence interval?

A response percentage calculated in a study cohort is an estimate of the response proportion in the population from which that cohort was drawn. A confidence interval conveys uncertainty around that estimate. It is not a guarantee that the true response proportion lies within the particular interval, and it does not remove limitations caused by a small or selected study population. The registry specifies a 90% confidence interval for the primary response rate.

The stated method is the Wilson score interval. As a general statistical explanation, the Wilson method is designed for a proportion and tends to behave more appropriately than a simple normal approximation when the sample is limited or the proportion is near a boundary. Its interval still depends on the observed number of responders and the denominator. Because neither the response count nor the evaluable denominator is reported, no interval can be interpreted from the registry information.

How is response determined?

The registry states that revised RECIST version 1.1 was used to determine response and progression, with specific criteria for tumor subtypes. It notes 2-dimensional measurements for CNS tumors. In general, standardized response criteria make tumor assessments more reproducible by specifying how measurements and categories are applied. The details for the different tumor subtypes matter in a study that includes a broad range of conditions. The registry record does not provide the participant-level assessments or the final response classifications.

The endpoint refers to evaluable patients, but the criteria for evaluability are not reported in the registry record. This matters because a response percentage depends on its denominator. If some enrolled participants lack an evaluable assessment, the count of enrolled participants may differ from the population used to calculate the response rate. The record reports enrollment of 5, but it does not state the response-evaluable count, treatment exposure, or reasons for any missing assessments.

What does the single-group design allow?

In a single-group study, the response rate describes outcomes among participants receiving the study treatment. Without a comparator arm, there is no concurrent estimate of what would have happened under another treatment or under a control condition. General statistical interpretation of a single-group estimate must therefore distinguish the observed outcome proportion from a causal treatment effect. Differences in disease type, prior treatment, prognosis, and follow-up could influence outcomes, but their distributions are not reported.

The study is open-label, with masking listed as none. Lack of masking does not change the mathematical definition of the response rate, but in general, knowledge of treatment assignment can be relevant to assessment and reporting. The record states the response criteria used; it does not report whether assessments were independently reviewed or how any disagreements were handled. Such details are not reported in the registry record.

How should safety counts be read?

The safety information separates serious adverse events from other adverse events. It gives the number at risk and the number affected for each group. These are descriptive counts, not comparative estimates, because the study has no control group. General safety interpretation also depends on event definitions, observation time, severity grading, attribution, and whether a participant can contribute more than one event or term. The registry record does not report all of those details.

The listed serious-event terms have percentages, but the record does not provide the term-specific denominators or explain whether participants could appear under multiple terms. A term percentage should not be treated as a percentage of all adverse events unless its denominator and counting rules are clear. The deaths are listed separately in the safety data; the record does not specify their causes or whether they were attributed to treatment.

What does the planning illustration represent?

The sample-size assumptions describe a planning illustration computed from an observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Time-to-event planning is described in total events using the Schoenfeld approach, while other planning outputs are described as participants per arm.

Those assumptions do not turn this single-group trial into a two-arm study, and planning illustrations are not observed power. The registry record does not report an observed primary response effect from which to assess such an illustration. It also does not report a sample-size justification for the trial, or a protocol-based power calculation. The planning assumptions should therefore be read as a separate statistical illustration, not as evidence that the study was designed to detect a particular treatment effect.

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 (Tipifarnib)")
n      <- c(5)
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 (Tipifarnib)  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists objective response rate as the primary outcome and names progression-free survival and the percentage of patients experiencing grade 3 or higher adverse events as secondary outcomes. It reports 5 outcome measures overall, but the posted information does not give results for the primary or secondary outcomes. It records no analysis results. The statistical plan for handling multiple outcomes or multiple statistical tests is not reported in the registry record.

Multiplicity arises when more than one outcome, comparison, subgroup, or analysis is examined. In general, the more opportunities there are to identify a statistically notable finding, the more important it is to know whether the analyses were prespecified and whether any adjustment or hierarchy was planned. The record does not describe a multiplicity strategy. It would therefore be inappropriate to assume that the primary and secondary outcomes were tested under a particular family-wise error or false-discovery procedure.

Missing data and analysis populations are also not described in sufficient detail. The primary endpoint is defined among evaluable patients, but the evaluability criteria, number evaluable, and handling of participants without response assessments are not reported. The record does not describe an intention-to-treat or other analysis population for the primary endpoint, nor does it explain how missing follow-up would be handled for progression-free survival or adverse-event outcomes.

These omissions do not establish that the trial lacked an analysis plan; they mean the relevant details are not reported in the registry record. Without the analysis population, missing-data rules, and prespecified multiplicity approach, readers cannot fully assess how the intended estimates were to be derived or how robust any future reported results would be to analysis choices.

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: disease progression (40.0%), dyspnea (20.0%), pleural effusion (20.0%).

The registry safety data list the treatment group with 5 at risk and 2 affected for serious adverse events. For other adverse events, it lists 5 at risk and 3 affected. The death count is 4. The most frequently listed serious-event terms are Disease progression at 40.0%, Dyspnea at 20.0%, and Pleural effusion at 20.0%.

These are descriptive registry figures. They do not by themselves show whether an event was caused by tipifarnib, whether the listed terms refer to unique participants, or whether one participant could contribute more than one event. The record does not report the event observation period, attribution rules, detailed severity information, or the term-specific denominators. The death count is not accompanied by causes or treatment attribution.

The serious-event terms should be read as coded safety categories rather than as an explanation of an individual participant’s course. Disease progression is listed among the serious terms, but the registry data do not provide enough context to interpret its timing relative to treatment or to the primary response assessment. The figures also cannot be compared with another treatment because this is a single-group study without a control arm.

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

The registry record establishes that this phase II study evaluated tipifarnib in a molecularly selected pediatric population and prespecified objective response as its primary outcome. It defines response using complete response or partial response among evaluable patients, describes the assessment criteria, and specifies a 90% Wilson score confidence interval. It also posts selected adverse-event counts and names progression-free survival and grade 3 or higher adverse events as secondary outcomes.

The record does not report the observed response rate, response count, evaluable denominator, confidence interval, progression-free survival result, or grade 3 or higher adverse-event result. Therefore, the posted information does not show how many participants responded or how precisely a response rate was estimated. It does not support a conclusion that tipifarnib did or did not produce a particular level of tumor response.

Even if a response estimate were available, a single-group design would describe outcomes in the treated cohort rather than provide a randomized comparison. It could not, on its own, separate treatment effects from other influences on outcome. The broad range of eligible diagnoses adds another interpretive consideration: without diagnosis-specific enrollment and results, the record cannot show how outcomes vary across disease types.

The safety counts are similarly descriptive. Serious events, other events, listed serious-event terms, and deaths are recorded, but event attribution, timing, causes of death, and several counting details are not reported. The counts should not be interpreted as proof that treatment caused an event or as a comparative safety estimate.

The registry’s study status and dates provide administrative context, not a substitute for outcome analyses. The study is listed as active, not recruiting, with primary completion dated 2024-03-31. Those details do not supply missing efficacy estimates or resolve uncertainty about safety. The appropriate reading is that the record specifies a clinical question and some safety information, while the main efficacy results and key analysis details remain unreported.

14. Why This Trial Matters Statistically

This trial is statistically notable for selecting participants by a molecular feature across a broad set of pediatric tumor types and disorders. That design asks a treatment question in a biologically selected population rather than restricting enrollment to one diagnosis. Statistically, however, a broad eligibility set can make the enrolled cohort heterogeneous. Diagnosis-specific enrollment and outcome summaries would help readers understand whether an overall response estimate represents a common pattern or combines different clinical groups; those details are not reported in the registry record.

The study is also a single-group phase II trial. A response proportion can be a useful descriptive endpoint in an early treatment study, particularly when the question is whether objective tumor shrinkage is observed in a selected population. Its interpretation remains distinct from a controlled estimate of comparative benefit. The lack of a control group means the study design does not directly estimate what outcomes would have been under an alternative treatment.

Precision is especially important when enrollment is 5. A proportion from a small cohort can shift substantially with the outcome of an individual participant, and its confidence interval communicates that uncertainty. The registry specifies the Wilson score method and a 90% confidence level, but does not post the response estimate or interval. This illustrates why an endpoint definition alone is not enough for statistical interpretation: the numerator, denominator, and uncertainty estimate are essential.

The record also illustrates the need to distinguish a planned analysis from posted evidence. It identifies secondary outcomes and provides selected safety counts, yet does not report primary or secondary outcome analyses. In the absence of those analyses, the trial’s statistical importance lies in its molecularly selected design and prespecified outcome framework, not in a result that cannot be assessed from the registry record.

15. Limitations

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

Enrollment is 5, and the registry does not report how participants are distributed among the listed diagnoses. With a small cohort spanning many disease types, an overall response estimate, if reported, could be difficult to interpret as representative of any particular diagnosis. The record does not provide diagnosis-specific response results or participant characteristics that would help contextualize the cohort.

The primary endpoint is defined among evaluable patients, but the evaluability rules and the number of evaluable participants are not reported. The registry also does not report response counts, the observed response rate, or the specified confidence interval. These omissions prevent assessment of the primary endpoint’s result and precision.

The single-group, unmasked design has no concurrent comparator. It can describe outcomes in participants who received tipifarnib, but cannot directly estimate a difference from another treatment or control. The record does not provide enough information about prior treatment, participant-level follow-up, or outcome assessment procedures to explore potential sources of variation.

Safety interpretation is limited by the absence of reported event-attribution rules, observation duration, term-specific denominators, and causes of death. The listed event counts and percentages should not be treated as causal estimates or as a comparison with another regimen. The registry does not report the results for the listed progression-free survival or grade 3 or higher adverse-event outcomes.

Finally, analysis details concerning missing data, analysis populations, multiplicity, and the trial’s own sample-size justification are not reported in the registry record. The listed planning assumptions do not substitute for a protocol-specific design justification. Together, these limitations mean the posted record supports a description of the study plan and selected safety data, but not a full evaluation of efficacy, precision, or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial — NCT04284774.
• Registry record last updated 2026-10-16; status last verified 2026-10.
• Results first posted 2025-06-03.
• 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

NCT04284774 is a National Cancer Institute-sponsored phase II Pediatric MATCH subprotocol of tipifarnib for pediatric patients with tumors harboring HRAS genomic alterations. It is a single-group, open-label study with enrollment of 5. The listed regimen is tipifarnib twice daily on days 1-7 and 15-21, repeating every 28 days for up to 26 cycles (2 years), subject to disease progression or unacceptable toxicity.

The primary endpoint is objective response rate, defined as the percentage of evaluable patients whose best response is complete response or partial response, assessed through up to 2 years from study entry. The registry specifies revised RECIST version 1.1 and a 90% Wilson score confidence interval. It does not report the response estimate, response count, evaluable denominator, or interval.

Progression-free survival and grade 3 or higher adverse events are listed as secondary outcomes, without posted results. Safety information includes serious and other adverse-event counts, listed serious-event terms, and 4 deaths. The study status is active, not recruiting; primary completion is dated 2024-03-31.