A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) (NCT01286818), a na phase 1 study. The primary outcome is Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period.

2. Clinical Question

The study’s primary question was whether dose-limiting toxicities occurred during the initial treatment period when ramucirumab was given with FOLFIRI to Japanese participants with metastatic colorectal carcinoma. The official title describes participants whose disease had progressed during or after first-line combination therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. The stated primary objective was to investigate safety and tolerability, rather than to establish a comparative treatment effect.

This is a safety-focused question in a small, single-group study. It does not compare the combination with another treatment or with no treatment. The registry record lists additional outcomes concerning anti-IMC-1121B antibodies, ramucirumab pharmacokinetics, and best overall response. Those outcomes do not change the stated primary question, and their results are not reported in the registry record.

3. Trial Design

The registry record identifies this as a Phase 1 study, with the official title describing it as Phase 1b. It was a single-group study with no masking. Allocation is recorded as not applicable, and there is no like-for-like control group. Six participants were enrolled. The study is listed as completed; its recorded start was 2011-02 and its primary completion was 2012-02.

All participants were assigned to the listed group, FOLFIRI plus ramucirumab (IMC-1121B). The treatment components named in the record are ramucirumab, irinotecan, levofolinate, and 5-fluorouracil. The arm description contains no additional detail. The registry record does not report a protocol rationale for the treatment schedule or a sample-size justification.

The primary endpoint concerns dose-limiting toxicities during the assessment period from Day 1, Cycle 1 through Day 1, Cycle 3. One cycle is defined as 14 days. The DLT population is defined as enrolled participants who either completed the first 3 administrations of study medication or discontinued study medication because of a DLT during that period. That definition identifies the population intended for the endpoint; the number included in the endpoint analysis is not reported in the registry record.

Secondary outcomes listed in the record include immunogenicity, several measures of ramucirumab concentration and disposition, and best overall response. The record lists 9 outcome measures and 0 analyses. Statistical methods beyond the stated planning assumptions are not reported in the registry record.

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: Eight (8) participants signed the informed consent.

Overall Study

Analysis population for the primary outcome, as defined in the registry: DLT population: All enrolled participants who either completed the first 3 administrations of study medication or discontinued study medication due to a DLT during the DLT assessment period (Day 1, Cycle 1 through Day 1, Cycle 3).

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 population: Participants who received any quantity of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period, measured over Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days).

The primary endpoint counts participants who experienced any dose-limiting toxicity during the defined assessment period. A DLT was an adverse event possibly related to study drug that met specified criteria based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. The assessment ran from Day 1, Cycle 1 through Day 1, Cycle 3, with each cycle lasting 14 days.

The criteria covered selected severe blood-count abnormalities, infection with a low neutrophil count and fever requiring intravenous antibiotics, severe thrombocytopenia or bleeding requiring platelet transfusion, specified coagulation abnormalities, severe or uncontrolled hypertension, and severe non-hematologic toxicity. They also included urine protein above 3 grams per 24 hours and study-drug toxicity that delayed Cycle 3, Day 1 treatment until Day 44 or later. Grade 3 or Grade 4 infusion-related reactions due to ramucirumab or FOLFIRI were explicitly excluded from the DLT definition.

General statistical explanation: a participant count is a binary-outcome summary. Each participant either meets the stated event definition during the assessment period or does not. Such an endpoint gives a direct description of how many participants met the safety criterion, but its interpretation depends on the event definition, the analysis population, and the number of participants assessed. The primary DLT count is not reported in the registry record, so the endpoint cannot be summarized from the posted result information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: the type of endpoint determines what a statistical summary can say. A binary endpoint records whether each participant met a defined event criterion. The primary outcome in this study is a participant count: the number with any qualifying DLT during a specified assessment period. To interpret such a count, readers need both the number meeting the criterion and the number assessed under the relevant analysis-population definition. The registry record gives the definition of the DLT population but does not report the primary outcome count or the number analyzed.

What does a participant count describe?

A count describes the observed number of participants meeting the endpoint definition in the analyzed group. It is not, by itself, a comparison of treatments. A rate or proportion can sometimes help describe the event frequency, but no new rate can be derived because the primary DLT count and analysis denominator are not reported. No primary-endpoint estimate or confidence interval is reported in the registry record.

General statistical explanation: a confidence interval expresses uncertainty around an estimate under a specified statistical model. It is not a guarantee that the true value lies within the interval, and it does not remove limitations in study design or data collection. With limited observations, estimates can be imprecise. When no interval is reported, the reader cannot use the registry record to assess the statistical precision of the primary endpoint estimate.

Why does the endpoint definition matter?

The DLT definition determines which events count toward the primary outcome. Here, the definition includes adverse events possibly related to study drug that meet listed severity or treatment-delay criteria, while specifically excluding Grade 3 or Grade 4 infusion-related reactions due to ramucirumab or FOLFIRI. An event that does not meet the definition would not count as a DLT for this endpoint, even if it were recorded elsewhere as an adverse event. The assessment window also matters: the primary endpoint covers Day 1, Cycle 1 through Day 1, Cycle 3, not an unspecified period of follow-up.

The DLT population is defined as enrolled participants who completed the first 3 administrations or discontinued study medication because of a DLT during the assessment period. This definition is relevant because exclusion of participants who stop treatment for other reasons could affect interpretation of an event count. The registry record does not report how many participants met the population definition or how any other incomplete observations were handled.

What can a single-group analysis establish?

General statistical explanation: a single-group analysis can describe outcomes observed in the treated participants. It does not provide a randomized estimate of the difference between the study regimen and an alternative. Without a concurrent comparator, observed changes or events cannot be attributed uniquely to the treatment combination using a between-group contrast. The design also has no masking, according to the registry record. The record does not report procedures intended to reduce the potential influence of knowledge of treatment assignment on outcome assessment.

The registry record lists no analyses. It does not report a statistical analysis plan, a hypothesis test for the primary endpoint, or an interval estimate. The study’s stated primary objective is to investigate safety and tolerability; the posted record does not provide enough detail to reconstruct additional inferential procedures.

How should planning calculations be read?

The registry record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those assumptions describe hypothetical planning calculations, not the actual single-group design, which has no two-arm comparison. The numerical planning results are not reported in the registry record. Such illustrations are not observed power and do not describe what happened to the enrolled participants. General statistical explanation: sample-size planning depends on the chosen outcome, effect, variability or event frequency, allocation, and analysis method. Changing assumptions can change the resulting planning estimate; a calculation does not guarantee that a study will attain a particular level of precision.

Because the primary result and inferential analyses are not reported, the registry record does not allow readers to evaluate a fitted statistical model, assess an estimated treatment effect, or verify any statistical test. The appropriate statistical reading is therefore descriptive and limited to the outcomes and counts that are actually recorded.

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("FOLFIRI Plus Ramucirumab (IMC-1121B)")
n      <- c(6)
events <- c(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  FOLFIRI Plus Ramucirumab (IMC-1121B)  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary DLT outcome and secondary outcomes involving immunogenicity, ramucirumab pharmacokinetics, and best overall response. It lists 9 outcome measures and 0 analyses. A method for handling multiplicity across outcomes or analyses is not reported in the registry record. General statistical explanation: when several outcomes are examined, the chance of at least one apparently notable result can depend on how many tests are performed and how they are interpreted. A prespecified multiplicity strategy can help clarify which comparisons are confirmatory and how uncertainty should be understood. No such strategy is reported.

Missing-data methods are not reported in the registry record. The DLT population definition states which enrolled participants qualify based on completing the first 3 administrations or discontinuing because of a DLT, but it does not report how many participants met that definition or how other missing observations were treated. Without those details and the primary outcome count, completeness of endpoint assessment cannot be evaluated from the posted record.

The registry record does not report a separate analysis population for the secondary outcomes, nor does it describe analysis exclusions or sensitivity analyses. The primary DLT population is defined, but the number included in the analysis is not reported. General statistical explanation: population definitions and missing-data handling matter because they determine which participants contribute to an estimate and can affect how representative that estimate is of the enrolled group. The available information does not permit assessment of those issues beyond the stated DLT population definition.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The serious adverse-event summary records 0 events among 6 participants at risk in the FOLFIRI plus ramucirumab group. It records other adverse events in 6 among 6 participants at risk. The record does not list serious-event terms, and a death count is not reported in the registry record.

These are observed counts in the study group, not comparative estimates. The serious-event count does not establish that serious events are impossible or that the regimen has no safety risks. General statistical explanation: when the number of participants observed is limited, even an observed count of zero leaves uncertainty about the frequency of events beyond the study group. The registry record does not report an interval estimate for these adverse-event counts.

The primary endpoint is not interchangeable with the broader adverse-event summary. DLTs follow a specific definition, including an assessment period and criteria for severity and possible relation to study drug. The adverse-event summary reports separate serious and other adverse-event counts. The primary DLT result is not reported in the registry record, so the adverse-event counts cannot substitute for it.

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

The posted information describes a completed Phase 1 study with a single group of six enrolled participants receiving FOLFIRI plus ramucirumab. Its primary objective was to investigate safety and tolerability, and its primary endpoint was the number of participants experiencing a DLT during the defined assessment period. The registry record does not report that primary count. Thus, the central endpoint cannot be quantified from the posted results.

The adverse-event summary reports 0 serious adverse events among 6 participants at risk and other adverse events in 6 among 6. Those counts describe the participants included in that summary. They do not provide a comparison with another treatment, and they should not be interpreted as precise estimates of event frequency in a broader population. The record does not report a death count or serious-event terms.

General statistical explanation: a trial result is interpreted in light of its design, endpoint definition, analysis population, and uncertainty. A single-group study can report what was observed in its participants, but it cannot provide the same direct comparative evidence as a randomized controlled comparison. Here, no comparative treatment effect is reported. The record also does not report results for the listed pharmacokinetic, immunogenicity, or best overall response outcomes.

Accordingly, the registry entry supports a description of the study’s purpose, design, endpoint definition, and posted adverse-event counts. It does not establish a treatment benefit, a lack of benefit, or a comparative safety profile. Those conclusions cannot be drawn from the outcome information reported in the registry record.

14. Why This Trial Matters Statistically

Statistically, this study illustrates how design and endpoint definition shape the conclusions that can be drawn. The registry describes a Phase 1, single-group study with six enrolled participants and a primary safety endpoint defined around qualifying toxicities during a specified treatment period. The careful criteria matter: the endpoint includes particular adverse events and explicitly excludes certain infusion-related reactions. A count is meaningful only when readers know what counted as an event and which participants were considered in the analysis.

The study also illustrates the limits of small, uncontrolled datasets. General statistical explanation: a small cohort can provide an account of observed events, but it typically offers limited precision for estimating uncommon outcomes. A single group cannot provide a randomized treatment contrast. These design features are not defects in the arithmetic; they set boundaries on what the data can answer.

The posted record is also a reminder that an endpoint definition is not a result. Although the DLT outcome and analysis population are described, the primary DLT count is not reported. Without that result, readers cannot assess the central safety endpoint. The adverse-event summary contributes descriptive information, but it does not fill that gap because the broader adverse-event categories are not the same as the defined DLT endpoint.

Finally, the listed secondary outcomes span antibody measurements, pharmacokinetics, and best overall response. Their presence identifies additional questions the study intended to examine, while the absence of results and analyses in the registry record limits statistical interpretation of those questions. Clear separation of reported outcomes, missing results, and design-based limits helps prevent a descriptive record from being read as stronger evidence than it contains.

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 principal limitation for interpreting the primary endpoint is that its participant count is not reported in the registry record. Although the DLT criteria, assessment window, and DLT population definition are described, the number meeting the endpoint and the number analyzed are not reported. The record therefore does not permit an estimate of the primary DLT frequency or its precision.

The study enrolled six participants and had a single group, with no comparator and no masking. These features limit what can be inferred about comparative outcomes. The participant population is described as Japanese subjects with metastatic colorectal carcinoma progressive during or following specified first-line combination therapy; conclusions from this record cannot automatically be extended to populations outside that description.

Results for the listed secondary outcomes are not reported in the registry record. A statistical analysis plan, handling of missing data, multiplicity procedures, interim analyses, and sample-size justification are not reported in the registry record. The record lists 0 analyses. The adverse-event summary is descriptive, and its counts do not replace the missing primary endpoint result. These limitations leave the statistical evidence in the registry entry incomplete for assessing the study’s stated primary question.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) — NCT01286818.
• Registry record last updated 2014-10-06; status last verified 2014-10.
• Results first posted 2014-10-06.
• 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

This completed Phase 1 study evaluated FOLFIRI plus ramucirumab (IMC-1121B) in Japanese participants with metastatic colorectal carcinoma. Six participants were enrolled in a single group, with no masking and no separate comparator. The stated primary objective was to investigate safety and tolerability.

The primary endpoint was the number of participants experiencing a qualifying DLT from Day 1, Cycle 1 through Day 1, Cycle 3; one cycle was 14 days. The primary DLT count is not reported in the registry record. The adverse-event summary reports 0 serious adverse events among 6 participants at risk and other adverse events in 6 among 6. Results for the listed secondary outcomes and statistical analyses are not reported in the registry record.