A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer (NCT00862784), a na phase 2 study. The primary outcome is Progression-Free Survival (PFS).

2. Clinical Question

3. Trial Design

This was a completed, open-label, multicenter phase 2 study of IMC-1121B (ramucirumab) combined with modified FOLFOX-6 as first-line therapy in participants with metastatic colorectal cancer. The registry lists an enrollment of 48. The study began in 2009-04 and primary completion was in 2011-04. The listed status is completed.

The design was single group, with allocation recorded as not applicable and masking recorded as none. All enrolled participants were assigned to the regimen rather than randomized between study treatments. This design can describe outcomes observed among participants receiving the combination, but it does not provide a concurrent control group for a direct treatment comparison. Differences between outcomes in this group and outcomes from another population would not, by themselves, establish that treatment caused the difference.

The regimen description says treatment was repeated every two weeks until disease progression, unacceptable toxicity, or withdrawal. The registry lists ramucirumab, oxaliplatin, folinic acid, and 5-FU among the interventions. The primary outcome population included participants who received any amount of study drug. The registry record does not report a separate analysis population beyond that definition.

The primary outcome was progression-free survival. Secondary outcomes included objective response rate, overall survival, duration of response, adverse events, and pharmacokinetic measures. The record lists 17 outcome measures, but records no analyses. A protocol-level explanation of the sample-size rationale, interim monitoring, and statistical analysis plan is 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: Completer was defined as any participant who died due to any cause or progression of disease, or any participant who was alive and on study but off study treatment at the conclusion of the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received any amount of study drug. The number of participants censored was 11.

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: All participants who received any amount of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Progression-Free Survival (PFS), measured over First dose to measured progressive disease or death due to any cause up to 28.1 months.

Progression-free survival measures the time from a defined starting point until disease progression is first observed or death occurs. In this study, the starting point was the first dose, and an event was the first observation of progression or death from any cause. The registry states that progression was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Its definition includes an increase of at least 20% in the sum of the longest diameters of target lesions, unequivocal progression of a non-target lesion, or a new lesion.

This time-to-event outcome is used because it accounts for both whether an event occurs and how long participants remain free of a recorded event. The median is the time by which half of the analyzed population has experienced an event, subject to the analysis method and censoring. It is a summary of the observed time-to-event distribution, not a measure of how much longer participants lived because of treatment.

Participants without recorded progression or death, or those who started new therapeutic anticancer treatment, were censored at their last radiographic tumor assessment according to the registry description. Censoring means that follow-up contributes information up to a specified point without treating that point as an event. The registry record identifies the primary outcome as a median with a 95% confidence interval, but does not report either estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Time-to-event outcomes describe the time until an event of interest. For this study, the event was the first documented progression or death from any cause, and follow-up began at the first dose. This approach uses information about the timing of events rather than reducing follow-up to a simple count of participants with progression. The registry describes the primary measure as a median and its uncertainty as a 95% confidence interval.

What does a median time-to-event estimate mean?

In general, the median is the point in the estimated time-to-event distribution at which half of the population is estimated to have experienced the event. It is a distribution summary, not an average duration and not an individual prediction. A median alone does not describe the full pattern of event times, and it does not tell whether a treatment caused the observed pattern. In this study, the registry names the median progression-free survival as the primary parameter but does not report its numerical value.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimate under the statistical method used. A narrower interval indicates greater precision than a wider interval, while the interval’s location describes the values compatible with the data and method. It is not a guarantee that the true value lies within a particular interval. The registry specifies a 95% confidence interval for the primary measure, but its endpoints are not reported in the registry record. Without the estimate and interval, readers cannot assess the observed duration or the precision of the primary result.

Why does censoring matter?

In general, censoring occurs when the event time is not observed during the available follow-up, so a participant contributes information through the last point at which their event status is known. It is not the same as observing that the event never occurred. The registry says that participants with no progression or death, or who started new therapeutic anticancer treatment, were censored at their last radiographic tumor assessment. It reports 11 censored participants for the primary outcome. The registry does not provide participant-level censoring times or details that would allow readers to evaluate the pattern of censoring.

Time-to-event methods rely on assumptions about how censored participants’ later outcomes relate to the information observed before censoring. In general, if censoring is associated with prognosis in a way not handled by the analysis, the estimated event-time distribution can be difficult to interpret. The registry record does not report enough analysis detail to assess the assumptions or the methods used to estimate the median and confidence interval.

How is progression defined?

The registry describes progression according to RECIST version 1.0. Progression could be based on an increase of at least 20% in the sum of the longest diameters of target lesions, unequivocal progression of a non-target lesion, or a new lesion. These criteria provide a stated basis for classifying progression, while the actual assessment depends on radiographic evaluations. The record says censoring was at the last radiographic tumor assessment, but does not report the schedule of assessments or further operational details.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed in its enrolled participants. It does not estimate a randomized between-group contrast because it has no concurrent control group. The outcomes can be influenced by participant characteristics, disease course, follow-up, and other aspects of care as well as by the study regimen. For that reason, a descriptive result from this design should not be interpreted as a causal treatment effect. This study is recorded as single group, with allocation not applicable and no masking.

The registry lists secondary outcomes including objective response rate, overall survival, duration of response, adverse events, and pharmacokinetic measures. A list of planned or registered outcomes is not itself a report of their results. The record lists 17 outcome measures but no analyses. It does not report the statistical analysis plan, adjustment for multiple outcomes, interim analyses, or a sample-size justification. Those details are not reported in the registry record, so the analysis choices and their implications cannot be assessed from this record alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures. The named secondary outcomes include objective response rate, overall survival, duration of response, ramucirumab-related adverse events and serious adverse events, and pharmacokinetic measures including maximum concentration, area under the concentration curve, and half-life. The record lists no analyses. It does not report how many of these outcomes were analyzed or which results were designated for formal inference.

When a study evaluates multiple outcomes, the chance of at least one apparently notable finding can increase if each is tested separately without accounting for multiplicity. In general, a prespecified hierarchy or adjustment method can help define how multiple results should be interpreted. The registry record does not report whether a multiplicity strategy was used, whether outcomes were prioritized beyond naming PFS as primary, or how secondary analyses were handled. It would be inappropriate to infer a method from the outcome list alone.

The primary outcome description identifies a population of all participants who received any amount of study drug. It also states that 11 participants were censored. The record does not report a detailed accounting of exclusions, missing assessments, reasons for censoring by participant, or sensitivity analyses for missing follow-up. The description explains censoring at the last radiographic assessment for participants without progression or death or those who started new therapeutic anticancer treatment, but it does not give further missing-data methods.

The registry record does not report an interim-analysis plan, stopping boundaries, or the rationale used to select the enrollment. These matters are not reported in the registry record. Without an analysis plan and complete numerical results, readers cannot determine how missing data, multiple outcomes, or interim monitoring may have affected statistical inference.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ovarian torsion (4.3%), disease progression (4.2%), pyrexia (4.2%), pulmonary embolism (4.2%), coagulopathy (2.1%).

The adverse-event group lists 48 participants at risk. It reports 18 participants with related serious adverse events and 47 with other related adverse events. These are participant counts for the study group, not comparisons with a control group. Because the study had no concurrent comparator, the counts alone cannot show whether the regimen changed the risk of an event relative to another treatment or to no treatment.

The registry also lists serious-event terms with percentages: ovarian torsion, 4.3%; disease progression, 4.2%; pyrexia, 4.2%; pulmonary embolism, 4.2%; coagulopathy, 2.1%; and febrile neutropenia, 2.1%. The terms and percentages describe entries in the registry’s adverse-event information. They should not be read as proof that the regimen caused each event. Disease progression is among the listed terms, and the record does not provide enough detail to interpret the event classifications or their relationship to the primary endpoint.

These figures do not replace information on event severity, duration, timing, management, or individual clinical context. The registry record does not report deaths in the adverse-event group. Counts and percentages are descriptive; they do not establish comparative safety.

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

The registry record establishes that a completed phase 2 study evaluated ramucirumab with modified FOLFOX-6 in a single group of participants with metastatic colorectal cancer. It defines progression-free survival as the primary outcome and specifies the time origin, event definition, progression criteria, and censoring description. These details help explain what the primary outcome was intended to measure.

The record does not report the median progression-free survival estimate or its 95% confidence interval. As a result, it does not give a numerical primary result that can be interpreted for magnitude or precision. The record also lists secondary outcomes but does not report analyses. A reader therefore cannot use this registry information to assess the numerical results for response, overall survival, duration of response, or the listed pharmacokinetic outcomes.

Even if an outcome estimate were available, the single-group design would limit causal interpretation. Without randomization to a concurrent comparator, observed time without progression or death cannot be separated from the influence of participant characteristics, the natural course of disease, follow-up, and other care. The study can describe its participants’ observed outcomes, but it does not provide a controlled estimate of how outcomes would differ under another treatment.

The safety figures describe reported events in the treated group. They do not establish that the regimen caused an event or that the frequency would be higher or lower under another approach. The serious-event terms and percentages should be interpreted as descriptive registry entries, not as comparative evidence.

In short, the registry record documents the study question, design, outcome definitions, and some safety counts, but leaves the primary numerical efficacy result and its uncertainty unreported. It does not demonstrate a treatment benefit or lack of benefit, and it does not support a comparative conclusion. Those limits reflect what is available in the registry record rather than a conclusion about results that are not reported there.

13. Why This Trial Matters Statistically

This study illustrates why a registered endpoint definition and a numerical outcome estimate serve different purposes. The definition of progression-free survival clarifies the event, time origin, progression criteria, and censoring approach. Those details are essential for understanding what a reported result would represent. However, without the median and its confidence interval, the registry record does not provide the main quantitative summary needed to assess the observed outcome or its precision.

The single-group design is also statistically consequential. It can describe outcomes in participants receiving the regimen, but it cannot create a randomized contrast where none exists. A comparison to external outcomes would be vulnerable to differences in populations, assessment, follow-up, and care. Recognizing that limitation prevents descriptive outcomes from being mistaken for evidence of a causal treatment effect.

The record also demonstrates the value of distinguishing outcome registration from analysis reporting. It lists 17 outcome measures and no analyses. Naming outcomes tells readers what was tracked or specified in the registry, but does not show which analyses were completed, how results were estimated, or how multiple outcomes were handled. The absence of a reported analysis plan further limits the ability to evaluate those choices.

Finally, the censoring information and safety counts need contextual interpretation. The record reports 11 censored participants for the primary outcome and adverse-event counts in the single study group. Censoring affects the information available about event timing, while safety counts without a comparator remain descriptive. Together, these features make transparent reporting of estimates, uncertainty, analysis methods, and follow-up especially important for statistical interpretation.

14. 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 from the registry record is that the numerical primary outcome is absent. Although progression-free survival is defined as a median with a 95% confidence interval, neither the median nor the interval is reported. The record therefore does not allow assessment of the observed outcome’s magnitude or precision.

The single-group design has no randomized comparator, so it cannot estimate a controlled treatment difference. The open-label design also means masking was absent. The record does not report details about the conduct of outcome assessment beyond the use of RECIST version 1.0, and does not report an assessment schedule or other procedures that would help evaluate measurement and follow-up.

The record reports 11 censored participants, but does not provide their individual follow-up times or reasons in sufficient detail to evaluate the censoring pattern. It also does not report sensitivity analyses or other missing-data analyses. A participant censored at the last assessment is not known from that point onward to have remained free of the event.

Additional analysis details are not reported in the registry record, including the sample-size justification, statistical analysis plan, interim-analysis approach, and multiplicity handling. The registry lists 17 outcome measures but no analyses, so it is not possible from this record to assess which analyses were conducted or how secondary outcomes were interpreted. These limitations concern the information reported in the registry record; they do not establish what may have been reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of IMC-1121B (Ramucirumab) in Colorectal Cancer — NCT00862784.
• Registry record last updated 2014-06-17; status last verified 2014-05.
• Results first posted 2014-06-17.
• 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.

18. Record Summary

NCT00862784 is a completed, open-label, multicenter phase 2, single-group study of IMC-1121B (ramucirumab) with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer. The registry lists an enrollment of 48 and describes treatment every two weeks until progression, unacceptable toxicity, or withdrawal.

The primary outcome was progression-free survival, measured from first dose to documented progression or death from any cause. Progression was assessed using RECIST version 1.0. The outcome population included participants who received any amount of study drug, with 11 censored participants reported.

The registry record does not report the median PFS estimate or its 95% confidence interval. It lists 17 outcome measures and no analyses. Adverse-event information includes 18 participants with related serious adverse events and 47 with other related adverse events among 48 at risk. Because there was no comparator, the study’s outcomes are descriptive rather than randomized comparative estimates.