Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Metastatic Colorectal Adenocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Metastatic Colorectal Adenocarcinoma (NCT01639131), a na phase 2 study. The primary outcome is Response Rate.

2. Clinical Question

3. Trial Design

This was a phase 2, open-label, single-group trial. The registry lists no masking and no allocation process, consistent with the absence of a separate comparison arm. The listed enrollment was 6. The study status is terminated; the reason for termination is not reported in the registry record.

The trial concerned gemcitabine and docetaxel for relapsed or refractory metastatic colorectal adenocarcinoma, with the title identifying tumors with methylated CHFR and/or a microsatellite instability phenotype. The sponsor was Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The recorded start date was 2012-09-10, and the primary completion date was 2016-10-03. These dates describe the registry timeline; they do not establish how long any individual participant received treatment or was followed.

The listed regimen used gemcitabine 800 mg/m2 on days 1 and 8 and docetaxel 70 mg/m2 on day 8 of each 21-day cycle. Filgrastim was listed for days 9 through 15, or pegfilgrastim 6 mg for day 9 or 10 of each cycle. The arm description ends before its treatment-duration statement is complete, so the stopping rule is not reported in the registry record.

Progression-free survival and overall survival were listed as secondary outcomes. A single-group design can describe outcomes observed among participants receiving the regimen, but it does not by itself separate treatment effects from other explanations for those outcomes. The small enrollment also means that estimates from this trial would be based on a limited number of participants. The registry record does not report a statistical plan or a numerical estimate for the primary endpoint.

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

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 Response Rate, measured over 9 months.

The primary endpoint was response rate, expressed as the number of participants achieving a complete response or partial response within the stated 9-month timeframe. Response was defined using RECIST 1.1. A complete response meant disappearance of all target lesions. A partial response meant a >30% decrease in the sum of target-lesion diameters. The definition also describes progressive disease as a >20% increase, and stable disease as a <30% decrease or <20% increase in that sum.

Response is a binary outcome at the participant level for this definition: a participant either meets the complete- or partial-response criterion or does not. A response endpoint is used in clinical studies to describe tumor change according to prespecified measurement criteria over a specified period. It can summarize whether participants crossed those criteria, but it does not by itself describe the duration of a response or establish what would have happened under a different treatment.

The registry record does not report how many participants achieved complete or partial response, the endpoint denominator, or a response-rate estimate. It also does not report a confidence interval or other uncertainty measure for this endpoint. Consequently, the endpoint definition is available, but the observed response result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome: participants who achieved a complete or partial response by RECIST 1.1 within 9 months. It does not report the analysis method used to estimate response, any uncertainty interval, or a hypothesis test. The explanations below are general statistical context, not a description of methods confirmed for this trial.

What does a response-rate estimate represent?

For a binary endpoint, a response-rate estimate is the proportion of assessed participants who meet the endpoint definition. In general, that proportion depends on two quantities: the number meeting the response definition and the number included in the analysis. The registry record does not report either quantity for this endpoint. Enrollment of 6 is not necessarily the same as the number assessed at the endpoint, so it cannot be used as a substitute denominator.

Complete and partial response are grouped together for the stated primary endpoint. This combines two response categories into one endpoint, rather than treating each category as a separate primary outcome. The RECIST definitions specify how changes in target lesions are classified; the registry record does not give participant-level measurements or response classifications.

Why would an uncertainty interval matter?

General statistical context: a confidence interval conveys the range of values reasonably compatible with an estimate under the assumptions of the interval method. For a response proportion, it would help readers distinguish a precise estimate from one that is highly uncertain. The interval depends on the observed count, the analysis denominator, and the chosen statistical method. None of these endpoint analysis details, nor an interval, is reported in the registry record.

Small samples generally produce limited precision. With only 6 participants listed as enrolled, even a complete endpoint analysis would have little information compared with a larger study. This does not determine what the response rate was; it explains why any estimate based on a small number of observations would need to be read with attention to uncertainty. No response estimate is reported, so no trial-specific precision assessment is possible.

What can a single-group design establish?

General statistical context: a single-group study can describe outcomes among the participants who received the regimen. It does not directly estimate a between-group treatment contrast, because there is no concurrent comparator. Differences between an observed outcome and an external expectation can be affected by population characteristics, outcome assessment, follow-up, and other factors. The registry record does not identify a comparator or an external benchmark for the response endpoint.

Open-label status means masking is listed as none. General context: when outcomes depend on assessment or reporting, lack of masking can be relevant to how outcomes are measured or recorded. RECIST provides defined response criteria, but the record does not report who assessed scans, whether assessments were independently reviewed, or how disagreements were handled. Those procedures are not reported in the registry record.

What do the secondary outcomes add?

Progression-free survival and overall survival are named as secondary outcomes. In general, time-to-event outcomes concern the time until a specified event, and their analysis can depend on follow-up duration and how participants without an observed event are handled. The registry record does not report numerical results, event counts, follow-up summaries, censoring details, or analysis methods for these outcomes. No time-to-event conclusion can be reconstructed from their names alone.

What does the statistical plan tell readers?

A statistical analysis plan can specify the analysis population, outcome definitions, handling of missing observations, estimator, uncertainty measures, and any planned comparisons. These details help readers understand how a reported estimate was obtained and what population it represents. The statistical plan is not reported in the registry record. The record also does not report a sample-size justification, interim analyses, or a prespecified inferential procedure. None should be inferred from the phase label or the stated endpoint.

General statistical context: a planning sample-size calculation uses assumptions about the effect to detect, variability or event frequency, significance level, power, and design. It is a planning exercise, not evidence that a trial achieved a particular level of power after results are observed. The registry record does not report the trial’s own sample-size justification. Any planning illustration based on an observed effect would likewise be distinct from the trial’s original design and from an observed efficacy result.

The posted registry information supports a clear description of the intended response definition and broad design, but not a reconstruction of the trial’s statistical analysis. Without the response count, analysis denominator, uncertainty estimate, and analysis methods, the response endpoint cannot be interpreted quantitatively.

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("Gemcitabine and Docetaxel")
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  Gemcitabine and Docetaxel  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 one primary outcome, response rate, and two secondary outcomes: progression-free survival and overall survival. It does not report how these outcomes were analyzed together, whether any additional outcomes were considered, or whether the statistical plan adjusted for multiple testing. Multiplicity procedures and planned testing order are not reported in the registry record.

General statistical context: when several outcomes or hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of the tests. This concern is different from the interpretation of a single descriptive estimate. Because the registry record does not provide analyses or a multiplicity plan, no claim about adjusted inference can be made.

The record does not report how missing response assessments were handled, which participants were included in each analysis, or how incomplete follow-up affected the secondary outcomes. It also does not state whether analyses used all enrolled participants, only participants who began treatment, or an evaluable subset. These analysis populations are not reported in the registry record.

General statistical context: missing outcome data can affect an estimate when the participants with observed outcomes differ systematically from those without them. The direction and size of any such effect depend on the missingness pattern and the analysis assumptions. Without participant flow, missingness details, and the analysis approach, the impact cannot be assessed. The enrollment figure alone does not resolve these questions.

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: fever (16.7%), sepsis (16.7%), neuropathic fever (16.7%).

The registry safety summary lists 6 participants at risk for the treatment group. Serious adverse events were recorded for 1 participant, other adverse events for 6 participants, and deaths for 4 participants. These are counts within a single group; there is no comparator arm in this trial.

The serious-event terms listed are fever, sepsis, and neuropathic fever, each at 16.7%. These percentages are registry entries for the named terms. The record does not provide further detail about event timing, duration, severity grading, recurrence, overlap between terms, or attribution to treatment. It also does not explain the relationship between the serious-event terms and the overall serious-event count.

General statistical context: safety counts describe events recorded in the study population, but interpretation depends on definitions, observation time, event attribution, and whether participants could experience more than one event. The registry summary does not provide those details. The listed deaths should not be treated as evidence that the treatment caused them; cause and attribution are not reported in the registry record. With 6 participants at risk, the summary is descriptive and does not support a stable estimate of comparative risk.

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

The registry record identifies a phase 2 investigation of gemcitabine and docetaxel in patients with relapsed or refractory metastatic colorectal adenocarcinoma associated with methylated CHFR and/or a microsatellite instability phenotype. It specifies a single-group, open-label design and defines the primary endpoint as complete or partial response under RECIST 1.1 at 9 months. It also lists progression-free survival and overall survival as secondary outcomes.

The record does not report a response count or response-rate estimate. It therefore does not show how many participants met the primary endpoint or how precise such an estimate might be. Nor does it report numerical results for the secondary survival outcomes. The listed enrollment of 6 is not a substitute for outcome results and does not establish how many participants were included in an endpoint analysis.

The design has no concurrent comparator. Even if numerical outcomes were available, a single-group study would describe outcomes among treated participants rather than directly estimate a treatment difference against a control group. The registry information does not support a conclusion that the regimen did or did not produce a particular clinical effect.

The adverse-event record contains descriptive counts and serious-event terms, but does not report attribution or the details needed to compare safety with another regimen. The terminated status is recorded, while its reason is not reported. These omissions limit what can be concluded about both efficacy and safety from this registry entry.

In statistical terms, the record provides endpoint definitions and design context, but not the principal numerical outcomes needed to evaluate the study’s stated efficacy question. The distinction matters: a trial’s objective and outcome definition describe what investigators intended to measure, whereas an observed estimate and its uncertainty are needed to characterize what the posted results show.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry gives a specific response definition based on RECIST 1.1, including criteria for complete and partial response, but does not report the number of participants who met those criteria. Without the count and analysis denominator, readers cannot interpret the response rate quantitatively.

The small listed enrollment is also statistically important. General statistical context: estimates from small groups are typically sensitive to the outcomes of individual participants and have limited precision. That consideration does not reveal the direction or size of an unreported response result; it underscores the importance of seeing the actual estimate and its uncertainty.

The single-group design highlights a separate issue. Describing outcomes in one treated group is not the same as estimating a comparative effect. Without a concurrent control, changes in outcomes cannot be directly contrasted with outcomes under another treatment within the study. This distinction remains important even when an endpoint is defined in detail.

Finally, the record’s terminated status and safety counts need context. The reason for termination, treatment attribution of adverse events, endpoint analysis populations, missing-data methods, and analysis plan are not reported in the registry record. Their absence makes it harder to judge how complete and interpretable the outcome reporting is. The case therefore demonstrates that registry design details can be informative while still leaving the central statistical result unavailable.

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 a numerical result for the primary response-rate endpoint. It gives no response count, analysis denominator, or uncertainty interval. Enrollment is listed as 6, but the record does not say how many participants were evaluable for response or how missing assessments were handled.

The trial had a single group and no masking. There was no concurrent comparator, so the design cannot provide a within-trial treatment contrast. The record does not report scan-review procedures or other details that would clarify how response assessments were conducted. The reason for termination is also not reported.

Progression-free survival and overall survival are named as secondary outcomes, but numerical results and analysis details are absent. The registry record does not report the statistical plan, sample-size justification, interim analyses, analysis populations, missing-data approach, or handling of multiple outcomes. These omissions prevent readers from assessing whether the reported analyses followed a prespecified approach.

The safety summary is limited to counts and selected serious-event terms. It does not report event attribution, timing, participant-level overlap, or the detail needed to characterize follow-up. The available information is therefore descriptive and cannot establish comparative safety. The treatment-duration text in the arm description is incomplete, so the regimen’s stopping rule is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Metastatic Colorectal Adenocarcinoma — NCT01639131.
• Registry record last updated 2022-08-10; status last verified 2022-08.
• Results first posted 2022-08-10.
• 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

The registry describes NCT01639131 as a phase 2, open-label, single-group trial of gemcitabine and docetaxel for relapsed or refractory metastatic colorectal adenocarcinoma with methylated CHFR and/or microsatellite instability phenotype. Enrollment was 6, and the status is terminated. The primary endpoint was response rate at 9 months under RECIST 1.1. Progression-free survival and overall survival were listed as secondary outcomes.

The record does not report numerical results for the primary or secondary outcomes, the analysis populations, or the statistical plan. It lists serious adverse events in 1 of 6 participants at risk, other adverse events in 6 of 6, and 4 deaths. The reason for termination and adverse-event attribution are not reported in the registry record.