A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer (NCT02613221), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy.

2. Clinical Question

3. Trial Design

This was a Phase I/II, completed, single-group study of panitumumab plus TAS-102. The registry lists enrollment as 56. It identifies Takeda as the sponsor and colorectal cancer as the condition. The listed start date is 2015-12-07 and the primary completion date is 2017-10-06. Allocation is recorded as NA, masking as none, and the model as single group. Thus, the design does not provide a randomized, masked comparison against a control treatment.

The treatment schedule combined panitumumab at 6 mg/kg every 2 weeks with oral TAS-102 at 35 mg/m² twice a day. TAS-102 was taken for 5 days, followed by a 2-day rest period within a 2-week cycle; the record also describes a 14-day rest period and 28 days per course. The primary endpoint was the count of participants with dose-limiting toxicity over up to approximately 1 month. The DLT Evaluation Set was defined as enrolled participants who received at least one dose in order to assess the recommended panitumumab dose, and its reported size was 6.

The registry lists overall survival, progression-free survival, response rate, duration of response, disease control rate, time to treatment failure and treatment-emergent adverse events among the secondary outcomes. It lists 9 outcome measures overall but no analyses. The record does not describe the statistical analysis plan, dose-escalation or dose-selection procedure, planned sample-size justification, interim analyses, or methods for handling missing outcome data. These aspects should not be inferred from the Phase I/II label or from the reported design fields.

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 with a historical diagnosis of RAS wild-type, unresectable, advanced/recurrent colorectal cancer were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT Evaluation Set; DLT Evaluation Set was defined as participants who were enrolled and received at least one dose of the study drug in order to assess recommended dose of panitumumab in combination with TAS-102 (Total number of DLT Evaluation Set was 6).

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.

Population: Safety Analysis Set, The safety analysis set was defined as all participants who received at least one dose of the study drug during the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy, measured over Up to approximately 1 month.

The primary endpoint counts participants with dose-limiting toxicity (DLT) during up to approximately 1 month. The registry says DLT was assessed using Common Terminology Criteria for Adverse Events version 4.03. Its definition included specified severe blood-count toxicities, febrile neutropenia, delay in starting Course 2 because of a treatment-related adverse event, and clinically significant non-hematologic toxicity at Grade 3 or higher, subject to stated exceptions for some gastrointestinal symptoms and electrolyte abnormalities.

As a general statistical concept, a DLT count is used in early treatment studies to describe whether prespecified toxicities occur within a defined assessment period. It can contribute to dose assessment, but a count alone does not describe the full range, timing or duration of adverse events. Interpretation also depends on who was eligible for the endpoint analysis and whether participants had enough follow-up to be assessed. The DLT Evaluation Set was defined in the record and included 6 participants.

The registry record does not report the observed DLT count. It therefore does not allow the primary endpoint result or its precision to be assessed. No confidence interval or other statistical analysis for this endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the design as single group, with allocation listed as NA and masking listed as none. These labels mean that the record does not describe assignment to competing treatment arms or masking of treatment. General statistical context: a control group can help distinguish treatment-associated outcomes from changes that may occur over time or from other influences. Without such a group, outcomes in the treated participants are descriptive rather than a direct estimate of comparative treatment effect.

What does a count endpoint tell us?

The primary outcome is a count of participants meeting the registry’s DLT definition during up to approximately 1 month. A count is a direct way to report how many people met a specified event definition in an analysis population. Its interpretation depends on the definition, observation period, and participants included. Here, the DLT Evaluation Set was defined as participants enrolled and receiving at least one dose of study drug to assess the recommended panitumumab dose; the registry reports 6 participants in this set. The observed DLT count is not reported in the registry record.

General statistical context: counts are often presented alongside the number of participants observed, so a reader can understand the scale of the result and the denominator. A count without its relevant analysis population can be ambiguous. Even when both are available, a count does not describe uncertainty as fully as an interval estimate might. No confidence interval for the DLT result is reported in the registry record.

What does a confidence interval mean?

General statistical context: a confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method used. It is not a guarantee about an individual participant’s outcome, nor does it establish that a difference is clinically important. For a proportion or event rate, an interval can help show how much the estimate may vary because the observed data are limited. The registry record does not report a confidence interval for the primary endpoint, and it lists no analyses from which one could assess the interval method or assumptions.

How should a single-group result be read?

General statistical context: a single-group study can document what occurred among participants receiving the study regimen. It lacks an internal control to estimate what would have occurred in comparable participants under a different regimen. Therefore, even a complete outcome count would not by itself demonstrate comparative benefit or harm. The Phase I/II designation and the stated aim of assessing the recommended panitumumab dose do not supply the missing statistical details about dose selection. The protocol and statistical plan are not reported in the registry record.

What can the safety counts establish?

The adverse-event record gives at-risk and affected counts for serious adverse events and other adverse events, as well as a list of serious-event terms and percentages. General statistical context: safety counts describe recorded events in a defined reporting framework. They do not, by themselves, establish causation. Attribution requires information about clinical assessment and the event’s relationship to treatment; timing and severity details also matter. These details are not fully reported in the registry record for this analysis.

The record lists 55 at risk and 13 affected for serious adverse events, and 55 at risk and 54 affected for other adverse events. These are registry summaries, not a complete narrative of each participant’s experience. The 6 deaths are listed without a cause or treatment relationship in the registry record. The listed serious-event terms and percentages should therefore be read as reported safety summaries, not as proof that the study treatment caused each event.

What analysis details are absent?

The registry lists 9 outcome measures and 0 analyses. It does not report the statistical analysis plan, methods for estimating secondary outcomes, confidence intervals, adjustment for multiple outcomes, missing-data procedures, or the analysis populations for the secondary endpoints. Those details affect how estimates should be interpreted and compared. They cannot be reconstructed from the study title, phase, enrollment or outcome names.

General statistical context: over-dispersion matters when count data vary more than a chosen statistical model expects. If a model assumes less variability than the data contain, uncertainty may be understated. The record does not identify a count model or provide data that would support evaluating over-dispersion, so no claim about its relevance to the sponsor’s analysis can be made. Likewise, any sample-size planning illustration based on an observed effect would be a hypothetical planning exercise, not observed power or a substitute for the trial’s own design rationale. The trial’s sample-size justification is not reported in the registry record.

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("Panitumumab + TAS-102")
n      <- c(6)
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  Panitumumab + TAS-102  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary DLT count and secondary outcomes such as overall survival, progression-free survival, response rate, duration of response, disease control rate, time to treatment failure and treatment-emergent adverse events. It lists 0 analyses. The registry record does not report a multiplicity procedure or explain how the primary and secondary outcomes were prioritized for statistical testing.

General statistical context: when several outcomes are examined, the chance of finding an apparently notable result by chance can increase if each is tested independently without a prespecified approach. A statistical plan may address this through an outcome hierarchy, adjusted testing, or a descriptive interpretation that does not treat every result as confirmatory. No such approach is reported, so the secondary outcomes cannot be characterized as confirmatory or exploratory based on the registry record alone.

The record also does not report missing-data methods, endpoint-specific analysis populations beyond the DLT Evaluation Set definition, or procedures for participants who did not complete follow-up. Such information matters because the set of observed participants and their follow-up can affect endpoint estimates. The registry enrollment figure of 56 and the adverse-event at-risk figure of 55 should not be used to fill in missing analysis-population details.

The primary endpoint result itself is not reported in the registry record. This means there is no posted DLT estimate whose precision, missingness or multiplicity treatment can be evaluated. It is also not possible to infer whether missing outcomes were absent, not analyzed, or simply not included in the registry entry.

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: febrile neutropenia (9.1%), colon cancer (5.5%), anaemia (1.8%), vomiting (1.8%), general physical health deterioration (1.8%).

The registry lists 55 participants at risk for serious adverse events and 13 affected. For other adverse events, it lists 55 at risk and 54 affected. It also lists 6 deaths. These figures are registry safety summaries and should be read with their separate at-risk fields; the record does not explain the distinction between the enrollment figure and the safety denominators.

The serious-event terms with listed percentages are febrile neutropenia at 9.1%, colon cancer at 5.5%, anaemia at 1.8%, vomiting at 1.8%, general physical health deterioration at 1.8%, and pyelonephritis at 1.8%. The registry record does not provide further details on timing, duration, severity beyond the serious-event designation, recurrence, or treatment attribution for these terms. The listing does not establish that the study treatment caused an event. The 6 deaths are not accompanied by causes or attribution details in the record.

General statistical context: adverse-event summaries depend on definitions, observation windows and reporting practices. A participant-level affected count does not convey the number of episodes or how long events lasted. Serious events and other adverse events are separate summaries and should not be combined into a total. No such combined count is reported in the registry record.

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

The registry establishes that this was a completed Phase I/II, single-group study of panitumumab combined with TAS-102 in patients with RAS wild-type advanced or recurrent colorectal cancer. It describes the dosing schedule, the primary DLT endpoint and a DLT Evaluation Set of 6 participants. It also lists secondary outcomes and descriptive safety counts. These details characterize the trial’s intended question and its recorded design.

The record does not report the primary DLT result. It therefore cannot establish from the posted information how many participants met the DLT definition. Although safety fields give counts for serious and other adverse events, those summaries do not provide the primary endpoint result and do not establish whether events were caused by treatment. The registry also does not report results for the listed survival, progression, response or treatment-failure outcomes in the registry record for this analysis.

The absence of a concurrent control group is important. General statistical context: outcomes observed in a single treated group cannot, on their own, show what would have happened to similar participants under another treatment. A direct comparative conclusion requires a suitable comparison and an analysis that accounts for the study design. Neither is described.

The registry’s completion status and enrollment entry do not fill these result gaps. Nor can the lack of listed analyses be treated as evidence that an outcome did or did not occur. Statistical precision, missing-data handling and multiplicity are not reported in the registry record. Accordingly, the available information supports a description of the study design and selected safety reporting, but not a conclusion about comparative efficacy, the magnitude of a treatment effect, or a fully characterized safety profile.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way its design frames the available evidence. It is identified as a Phase I/II, single-group study whose primary endpoint is a count of participants with DLT over up to approximately 1 month. The endpoint is tied to dose assessment, and the record specifies both a toxicity definition and a DLT Evaluation Set. Those features make the analysis population and the event criteria central to interpretation.

At the same time, the record does not report the DLT count or list statistical analyses. This distinction between a clearly described endpoint and an unavailable endpoint result is important: design details define what was meant to be measured, but do not reveal what was observed. The DLT Evaluation Set size of 6 cannot be substituted for an event count or interpreted as evidence about the frequency of DLT.

The single-group design also sets a limit on comparative inference. General statistical context: without a concurrent comparison group, observed outcomes can describe the participants’ experience but cannot isolate the effect of treatment from other explanations. This matters especially when a study includes several secondary outcomes, because outcome names alone do not establish results or statistical evidence.

The registry’s safety summaries illustrate another statistical distinction: participant counts and listed event percentages can describe recorded safety reporting, but do not fully convey event timing, recurrence, duration or attribution. The record reports such summaries without the analysis details needed to evaluate uncertainty or causal interpretation. Reading the trial statistically therefore requires separating the stated design and endpoint definitions from the outcome evidence that is not reported.

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 most direct limitation is that the primary endpoint result is not reported in the registry record. The stated DLT definition and the DLT Evaluation Set size of 6 do not reveal the number of participants with DLT. No estimate or confidence interval is available for interpreting the primary endpoint’s precision.

The design is single group, with allocation listed as NA and masking as none. There is no concurrent control group for a like-for-like comparison. The record also does not describe the statistical analysis plan, dose-selection procedure, sample-size justification, interim analyses, or analysis methods for secondary endpoints. These omissions prevent assessment of the planned inferential approach and whether the reported outcomes followed that plan.

The enrollment entry is 56, while adverse-event fields list 55 at risk. The registry does not explain this difference or specify whether the safety population and endpoint populations align. The DLT Evaluation Set is defined separately, and its reported size is 6. These populations should not be treated as interchangeable.

Safety reporting is limited to affected and at-risk counts, selected serious-event terms with percentages, and a death count. The registry entries in the registry record do not establish event timing, duration, recurrence, cause of death or treatment attribution. The record lists secondary outcomes but does not report their results in the registry record for this analysis. It also does not describe missing-data methods, multiplicity handling or follow-up completeness. These limitations restrict both statistical interpretation and the extent to which the recorded outcomes can be generalized beyond the study population.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer — NCT02613221.
• Registry record last updated 2019-07-31; status last verified 2019-07.
• Results first posted 2019-06-24.
• 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

NCT02613221 is a completed Phase I/II, single-group study of panitumumab plus TAS-102 in patients with RAS (KRAS, NRAS) wild-type, unresectable, advanced or recurrent colorectal cancer. Takeda is listed as the sponsor. Enrollment is recorded as 56; the start date is 2015-12-07 and the primary completion date is 2017-10-06.

The primary outcome is the number of participants with DLT over up to approximately 1 month. The DLT Evaluation Set included 6 participants, but the observed DLT count is not reported in the registry record. Safety fields list 13 affected of 55 at risk for serious adverse events, 54 affected of 55 at risk for other adverse events, and 6 deaths. The registry lists 9 outcome measures and 0 analyses. It does not report the primary endpoint result or statistical analysis details in the registry record for this analysis.