Pilot Study Using Molecular Profiling to Find Potential Targets & Select Treatments for Pts With Met br ca: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study Using Molecular Profiling to Find Potential Targets & Select Treatments for Pts With Met br ca (NCT01074814), a na early/phase 1 study. The primary outcome is Growth Modulation Index (GMI) Greater Than or Equal to 1.3.

2. Clinical Question

3. Trial Design

This was a completed, early phase 1, single-group pilot study in metastatic breast cancer. The registry lists allocation as not applicable and masking as none. There was no randomized control arm, so the treatment comparison was not between separately assigned groups. Instead, the primary endpoint compared each evaluable participant’s progression-free survival on molecularly selected therapy with time to progression on the participant’s last prior therapy.

The intervention was approved therapy assigned based on molecular profile and RPMA results. The official title describes molecular profiling using immunohistochemistry, fluorescence in situ hybridization, DNA microarray, and reverse phase protein microarray. The record states that 28 patients were enrolled and underwent tumor biopsy. Of these, 25 were treated on study with the selected treatment and were evaluable for the primary endpoint. The reason that the enrolled population differs from the evaluable population is not reported in the registry record.

The primary endpoint timeframe is listed as 6-20 weeks. Separately, the brief study summary describes the objective as determining the response rate, defined there as the percentage of patients with non-progression after 4 months on treatment. The primary-endpoint description instead focuses on GMI and identifies a threshold of at least 1.3. These descriptions are not identical, and the registry does not explain their relationship. The study started in 2010-03, reached primary completion in 2012-07, and is listed as completed.

Because the study has no concurrent randomized control group, its within-participant comparison does not isolate the effect of the selected therapy from other changes over time or differences between prior and current treatment periods. The design is suitable for describing what happened among the participants who received the selected therapy, but the registry does not establish a causal treatment effect.

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

Analysis population for the primary outcome, as defined in the registry: A total of 28 patients were enrolled and underwent tumor biopsy for the purposes of this study. 25/28 patients were treated on study with the MMP-selected treatment and were evaluable for the primary end point of GMI.

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 Growth Modulation Index (GMI) Greater Than or Equal to 1.3, measured over 6-20 weeks.

The primary endpoint is the number of participants with a Growth Modulation Index (GMI) greater than or equal to 1.3. GMI is defined as progression-free survival on molecularly selected therapy divided by time to progression on the participant’s last prior therapy. The endpoint therefore uses each participant’s previous treatment experience as a reference, rather than comparing outcomes with a separate control group.

The registry says the threshold was chosen because a 30% or greater improvement in progression-free survival compared with the previous time to progression would be considered clinically meaningful. This rationale describes the study’s chosen threshold; it does not establish that the threshold was reached. The endpoint timeframe is listed as 6-20 weeks, while the brief summary describes non-progression after 4 months as the response-rate objective. The registry does not clarify how these endpoint descriptions relate.

For a binary endpoint, each evaluable participant either meets the stated GMI threshold or does not. The resulting count or proportion can describe how often the threshold was met among the analyzed participants. Its interpretation depends on knowing the endpoint result, the analysis population, and the uncertainty around the estimate. The registry’s numerical count and any uncertainty interval are not reported in the registry record, so the endpoint’s observed frequency cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines a binary primary endpoint: whether a participant’s GMI is greater than or equal to 1.3. A binary endpoint classifies each evaluable participant into one of two categories: meeting the threshold or not meeting it. A count reports how many participants fall into the category of interest; a proportion relates that count to the relevant analysis population. The registry identifies 25 participants as evaluable for the primary endpoint, but does not report the count meeting the threshold or the corresponding proportion.

What does GMI compare?

GMI is defined as progression-free survival on the molecularly selected therapy divided by time to progression on the last prior therapy. It is therefore a ratio of two time-to-event measures from different treatment periods in the same participant. A value of 1.3 or greater was the stated threshold. The record explains that the threshold was selected to represent a 30% or greater improvement in progression-free survival relative to the prior time to progression that the study considered clinically meaningful. This is the protocol’s stated rationale, not a reported result.

General statistical context: a within-participant comparison can reduce some differences between people because each person serves as their own reference. It does not remove differences between treatment periods. Changes in disease status, timing, assessment, or other factors can affect the comparison. The registry does not report adjustment methods or details of how those factors were handled. It also does not describe how the two time-to-event measures were determined when an event was not observed during the relevant period.

How should uncertainty be considered?

General statistical context: an estimate from a sample is subject to uncertainty because another group of participants could produce a different result. A confidence interval is one way to express the range of values compatible with the data and a specified statistical procedure. Its width reflects precision, while its interpretation depends on the method and assumptions used. The registry record does not report a confidence interval for the primary endpoint, a p-value, or a numerical endpoint estimate. Precision cannot therefore be judged from the endpoint information in the registry.

General statistical context: a binary proportion is usually interpreted with reference to its denominator and uncertainty. The denominator matters because the result describes the population included in the analysis, not necessarily everyone enrolled. Here, the record identifies the evaluable population but does not report the endpoint count. It also does not say whether participants without an assessable endpoint were excluded, classified in a particular way, or handled through another method. Such handling is not reported in the registry record.

What does the design imply for analysis?

The study is recorded as single-group, with no masking and allocation listed as not applicable. There is no randomized parallel group against which to estimate a between-group contrast. The primary comparison instead uses each participant’s previous time to progression. General statistical context: a historical or within-person reference may be informative, but it is more vulnerable than randomization to differences in treatment periods and to the way outcomes are assessed. The record does not report a statistical model, covariate adjustment, or sensitivity analysis for the primary endpoint.

The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are assumptions for a planning illustration, not a description of the actual single-group trial design. The illustration is not observed power. It should not be read as evidence that the trial had a particular probability of detecting an effect, or as a substitute for the missing endpoint estimate and its uncertainty. Sample-size calculations are planning tools whose interpretation depends on their assumptions and on a target effect; they do not establish what the study observed.

General statistical context: over-dispersion refers to variability greater than a statistical model expects. It can matter for some count outcomes when observations vary more than the model allows, potentially making uncertainty estimates too optimistic if the model is not appropriate. The listed primary endpoint is binary, and the registry does not report an over-dispersion model or a count-based inferential analysis. There is no basis in the record to claim that over-dispersion was assessed or relevant to the reported endpoint.

The registry lists one primary outcome measure and one analysis, but does not provide a detailed statistical analysis plan or the numerical analysis result. Whether the analysis was prespecified in detail, how missing endpoint data were handled, and whether additional analyses were conducted are not reported in the registry record. The available design and endpoint descriptions clarify the question being asked, but not the full analytical procedure or the precision of the answer.

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("Intervention")
n      <- c(25)
events <- c(25)
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  Intervention  25  25  100.0  86.3  100.0  86.7  100.0  86.8  99.9

11. Multiplicity, Missing Data and Analysis Populations

The record identifies GMI greater than or equal to 1.3 as the primary endpoint and lists one outcome measure and one analysis. It does not report a detailed statistical analysis plan, a multiplicity adjustment, a hierarchy of endpoints, or a plan for controlling the chance of false-positive findings across analyses. The presence or absence of additional analyses beyond those listed is not reported in the registry record. Without a fuller analysis plan, it is not possible to determine how the primary endpoint related to other planned or exploratory outcomes.

The stated primary-endpoint population comprises 25 participants treated with the molecularly selected therapy and evaluable for GMI. The record also reports 28 enrolled participants who underwent tumor biopsy. It does not explain why the enrolled and evaluable populations differ. Reasons for non-treatment or non-evaluability, and the outcomes of participants not included in the primary analysis, are not reported in the registry record.

The handling of missing or incomplete measurements is also not reported. In particular, the record does not state how missing progression-free survival or prior time-to-progression information was treated, whether any participants were excluded because a comparison could not be made, or whether an alternative analysis was used. The primary-endpoint description does not establish whether the analysis population was defined before outcomes were known.

These omissions limit assessment of both potential selection effects and the robustness of the endpoint estimate. A result among evaluable participants may not describe the enrolled population if evaluability is related to outcomes or participant characteristics. The registry record does not provide the information needed to evaluate that possibility or to reconstruct the analysis population beyond the stated counts.

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 adverse-event record lists 25 participants at risk for serious adverse events and 0 affected. It separately lists 25 participants at risk for other adverse events and 5 affected. These are the posted counts for the intervention group; they should be read as separate categories rather than combined into a single total.

The registry does not list serious adverse-event terms. The death count is not reported in the registry record. A recorded zero for serious adverse events does not mean that no adverse events of any kind occurred: the separate other-adverse-event category records affected participants. The registry does not provide event descriptions, severity grades for the other category, timing, duration, or information about whether events were considered related to treatment.

General statistical context: safety counts describe the experience captured under the record’s reporting definitions and observation period. The number of affected participants alone does not describe the range or clinical importance of events, and a count does not establish whether treatment caused an event. The record does not report enough detail to assess event-level patterns or compare safety with an alternative treatment group. Because this was a single-group study, the safety figures are descriptive rather than a controlled comparison.

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

The registry describes a pilot study that used molecular profiling and RPMA results to select approved therapy for patients with metastatic breast cancer. Its primary question was whether the selected therapy could be associated with a GMI of at least 1.3 relative to the participant’s last prior therapy. The registry provides the endpoint definition and identifies the group evaluable for that endpoint, but the numerical GMI result is not reported in the registry record.

As a result, the record does not establish how often participants met the threshold, how precise an estimate of that frequency would be, or whether the stated clinical-meaningfulness criterion was met. The threshold’s rationale is a design choice described by the study; it is not a finding. The brief summary’s description of non-progression after 4 months also does not supply a numerical outcome, and the relationship between that description and the GMI endpoint is not explained.

The within-participant reference to prior time to progression gives the study a way to describe outcomes relative to each participant’s previous treatment period. It does not provide the protection against confounding that a randomized comparison can offer. Differences between treatment periods and other influences could contribute to an observed change. The registry does not report adjustments or other analyses that would address these concerns.

The safety record reports 0 participants with serious adverse events and 5 participants with other adverse events in the intervention group, with 25 at risk in each category. These figures are descriptive and lack event-level detail; the death count is not reported. They do not by themselves determine the cause, severity, or comparative safety of treatment.

Overall, the record documents the study design, endpoint rationale, evaluable population, and selected safety counts. It does not report the primary endpoint result or enough statistical detail to assess its precision. The study description should therefore be distinguished from evidence about the observed frequency of GMI threshold attainment or a causal treatment effect.

14. Why This Trial Matters Statistically

This study raises a statistical question about a treatment-selection strategy rather than simply comparing two assigned therapies. Molecular profiling and RPMA results were used to select approved therapy, and the primary endpoint compared outcomes on that therapy with time to progression on each participant’s last prior therapy. This makes clear why the choice of reference period is central to interpreting the result.

GMI translates that within-participant comparison into a threshold-based endpoint. Such a rule can make the study question concrete: whether the selected therapy’s progression-free survival reaches the prespecified relationship to the previous time to progression. The registry states that the threshold of 1.3 was chosen to represent a 30% or greater improvement regarded as clinically meaningful by the study. Statistical interpretation still requires the observed count, the analysis population, and a measure of uncertainty; these numerical endpoint results are not reported in the registry record.

The study also illustrates the difference between a planning assumption and an actual design. The registry describes a sample-size planning illustration using equal allocation between two arms, while the actual trial is identified as single-group with allocation not applicable. The illustration is not the trial’s own design and is not observed power. Keeping those concepts separate prevents a planning calculation from being mistaken for evidence about the study’s precision or success.

Finally, the distinction between enrolled and evaluable participants matters. The record reports 28 enrolled and biopsied, with 25 treated and evaluable for the primary endpoint, but does not explain the difference. Knowing how the analysis population was formed is important when judging whether the endpoint result, if reported, would represent the patients who entered the study. The registry’s missing outcome and analysis details leave these questions open.

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 does not report the numerical primary endpoint result. Although it defines the GMI threshold and identifies 25 evaluable participants, the number meeting that threshold, the corresponding proportion, and an uncertainty interval are not reported in the registry record. The endpoint therefore cannot be quantitatively assessed from the posted record.

The study has no randomized comparator group and no masking. Its primary comparison is against each participant’s last prior therapy, so treatment periods may differ in ways that are not controlled by randomization. The registry does not report methods for accounting for these differences, nor does it give a statistical model or sensitivity analyses. An observed within-participant comparison, if available, would not alone establish a causal effect.

The record states that 28 patients were enrolled and underwent tumor biopsy, while 25 were treated and evaluable for the primary endpoint. It does not explain why some enrolled participants were not included in the evaluable group or report their outcomes. The handling of missing or incomplete endpoint information is also not reported. These omissions prevent a full assessment of selection and missing-data effects.

The endpoint descriptions are not fully aligned: the brief summary refers to non-progression after 4 months, while the primary endpoint is GMI with a timeframe of 6-20 weeks. The registry does not explain how these descriptions correspond. It also does not report multiplicity procedures, a full analysis plan, or detailed adverse-event terms. Finally, the death count is not reported in the registry record, and the other-adverse-event category lacks event-level detail. These limits restrict interpretation of both efficacy and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study Using Molecular Profiling to Find Potential Targets & Select Treatments for Pts With Met br ca — NCT01074814.
• Registry record last updated 2023-09-28; status last verified 2022-11.
• Results first posted 2023-09-28.
• 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

NCT01074814 is a completed, early phase 1, single-group pilot study of molecular profiling to select approved therapy for metastatic breast cancer. The record lists no masking and no randomized allocation. It reports 28 patients enrolled and biopsied, with 25 treated using the molecularly selected therapy and evaluable for the primary endpoint.

The primary endpoint was the count of participants with GMI greater than or equal to 1.3, comparing progression-free survival on selected therapy with time to progression on the last prior therapy. The endpoint timeframe is listed as 6-20 weeks. The registry’s rationale describes the threshold as representing a 30% or greater improvement considered clinically meaningful by the study. The numerical endpoint result and its precision are not reported in the registry record.

The safety record lists 0 affected by serious adverse events and 5 affected by other adverse events, with 25 at risk in each category. Serious-event terms are not listed, and the death count is not reported. The record does not explain the difference between the enrolled and evaluable populations or provide a full statistical analysis plan.