This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Metformin Hydrochloride in Treating Women With Stage I or Stage II Breast Cancer That Can Be Removed By Surgery (NCT00984490), a na na study. The primary outcome is Change in Ki67 Levels Before and After Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00984490 |
| Phase | NA |
| Condition | Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanderbilt-Ingram Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Women with stage I or stage II breast cancer that could be removed by surgery. The registry record lists an enrollment of 5.
Intervention
The intended regimen was metformin hydrochloride, 850 mg orally twice daily for 7-21 days, with treatment discontinued 24-36 hrs before surgery. Laboratory biomarker analysis was also listed.
Comparator
The record describes a single-group trial and no randomized comparison. A like-for-like control group is not reported in the registry record.
Primary question
The planned question was whether Ki67 levels in breast tissue changed between the pre-treatment assessment and the assessment around surgery after metformin treatment. No Ki67 levels were determined, so the registry record contains no result for that question.
The trial focused on a short presurgical treatment period, with tissue measurements intended to describe a biomarker before and after treatment. Ki67 was to be assessed in surgically excised breast tissue by measuring the percentage of nuclei with positive staining and determining a mean score. The stated assessment timeframe was baseline and between 8-23 days.
The record also lists changes in circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 as secondary outcomes. It does not report results for these measures. Thus the clinical question is identifiable from the planned outcome and treatment description, but the posted results do not establish whether any biomarker changed during the treatment period. The record says that the trial closed due to slow accrual and that no Ki67 levels were determined.
3. Trial Design
This was a phase I presurgical study recorded as a single-group trial. Its purpose was to study metformin hydrochloride in women with operable stage I or stage II breast cancer. The allocation field is recorded as NA, and the masking field is NONE. The record does not describe random allocation or masking. Because this was a single-group study, it did not provide a randomized control comparison.
The Metformin arm description specifies 850 mg orally twice daily for 7-21 days, discontinued 24-36 hrs prior to surgery. Laboratory biomarker analysis is listed as another intervention. The planned primary endpoint compared breast tissue Ki67 measurements across the pre-treatment and presurgical period. The secondary outcomes named in the record concern circulating IGF-1 and IGFBP-3.
Enrollment was 5. The trial status is TERMINATED, and the stated reason for closure was slow accrual. The record lists a start of 2009-09 and primary completion of 2010-07. These registry fields describe the study record; they do not establish that every planned assessment was completed. In particular, the record explicitly states that no Ki67 levels were determined.
The registry record does not report a statistical analysis plan, a sample-size justification for the trial itself, or details of any comparator. The planning assumptions described for sample-size illustrations are not evidence that those assumptions were used to design this trial. Nor do they supply an outcome analysis when the planned primary endpoint was not measured.
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: Five patients enrolled on this study during the first nine months. Accrual continued to be slow causing its premature closing.
Overall Study
| Stage | Metformin |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: No Ki67 levels were determined. This clinical trial was closed due to slow accrual
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.
| Characteristic | Unit | Metformin |
|---|---|---|
| Participants analysed | 5 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 45 (SD 1) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Ki67 Levels Before and After Treatment, measured over baseline and between 8-23 days.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in Ki67 levels before and after treatment. The registry describes Ki67 assessment in pre-treatment, presurgery and post-treatment surgically excised breast tissue. The measure was the percentage of nuclei with positive staining, with scores ranging from a minimum of 0% to a maximum of 100%, and a mean score was to be determined. The timeframe was baseline and between 8-23 days.
In general, a tissue biomarker endpoint can be used to characterize a biological measurement over a defined treatment period. A before-and-after measure is intended to describe change within the study group. It does not by itself separate a treatment-related change from changes that could occur over time or for other reasons. Without a concurrent comparison group, interpretation of change would also be limited by the single-group design.
For this trial, the key issue is that the registry states no Ki67 levels were determined. Consequently, the planned endpoint has no reported baseline value, follow-up value, change estimate, or uncertainty measure in the registry record. The endpoint definition explains what the investigators intended to measure; it is not evidence that the measurement was collected or that a change occurred.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a small, single-group presurgical study that was terminated because of slow accrual. Its primary endpoint was change in breast-tissue Ki67 levels, but the record explicitly says that no Ki67 levels were determined. Therefore, the posted results do not provide an estimate of change in the primary endpoint. They also do not provide an uncertainty interval or a statistical test for that endpoint.
This absence of an endpoint result is different from a finding of no change. A finding of no change would require measurements and an analysis capable of estimating change. Here, the registry reports that measurements were not determined. It is therefore not possible to characterize the direction, size, or precision of a Ki67 change from this record.
The trial had no randomized comparison recorded. Even if before-and-after measurements had been available, a within-group pattern would not have offered the same basis for comparison as a concurrent control group. General statistical interpretation of a single-group change must consider the possibility that observed differences reflect time, measurement variation, or other influences, in addition to any treatment-related pattern. In this record, however, no primary endpoint measurements are available to assess.
The listed secondary outcomes are changes in circulating IGF-1 and IGFBP-3. The record does not report results for these outcomes. It lists 2 outcome measures and 0 analyses. The absence of reported analyses means there are no posted outcome estimates to compare across those measures or to use in evaluating consistency.
The adverse-event figures are distinct from the efficacy question. The record reports 0 serious adverse events among 5 at risk and 4 other adverse events among 5 at risk. Deaths are not reported in the registry record, and no top serious adverse-event terms are listed. These entries describe the posted safety counts; they do not provide an efficacy result or explain the nature of the other events.
The sample-size illustration assumptions are planning settings, not evidence that the trial had a particular level of power. They specify 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 fraction of the observed effect. The actual trial is described as a single-group study, and its primary outcome was not determined. Such planning assumptions cannot replace observed endpoint data or establish what the trial could detect in practice.
Overall, the record documents the planned question, regimen, trial status, and limited safety counts. It does not support an estimate of the primary biomarker effect. The appropriate statistical reading is that the primary outcome is unavailable, rather than that the treatment did or did not change Ki67.
9. Statistical Methods Explained
Statistical methods help distinguish a measured result from a planned question and clarify how much uncertainty surrounds an estimate. In this record, the most important methodological fact is that the planned primary outcome was not determined. That absence limits what can be learned from inferential statistics: a test statistic, effect estimate, or confidence interval for Ki67 change cannot be interpreted when the underlying Ki67 measurements are not reported.
What does a before-and-after endpoint estimate?
In general, a before-and-after endpoint compares measurements from the same study group at different times. Its estimate describes the observed within-group change over the specified period. When participant-level measurements are available, an analysis can account for the paired nature of the observations: each participant's follow-up measurement is related to that participant's baseline measurement. This can differ from comparing unrelated groups, because the analysis uses information about within-person change.
A within-group change is not automatically a causal treatment effect. Without a concurrent comparator, changes over time, measurement conditions, or other influences may contribute to the observed pattern. Randomized comparisons are designed to support a different kind of contrast by comparing groups assigned to different conditions. The record describes a single-group study, not a randomized comparison. In this case, the further limitation is that no Ki67 values were determined, so there is no within-group change estimate to interpret.
Why does precision matter?
In general, an estimate is more informative when its uncertainty is described. A confidence interval gives a range of values compatible with the data under the statistical procedure used. A narrow interval indicates greater precision than a wide interval, while an interval spanning values that imply different interpretations may leave substantial uncertainty. A confidence interval does not repair missing measurements, and it cannot be inferred from a planned endpoint description alone. The registry record does not report a Ki67 estimate or confidence interval.
A p-value, when reported, addresses how compatible the observed data are with a specified null model under the assumptions of the test. It is not a measure of effect size, clinical importance, or the probability that a hypothesis is true. No primary endpoint analysis is reported, so there is no p-value for Ki67 change to interpret. The record lists 0 analyses.
What do the planning assumptions mean?
The record describes sample-size illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the target effect is a stated fraction of the observed effect. These are planning assumptions, not descriptions of the completed trial's analysis. The illustrations are not observed power. They also do not show that the original study used those settings, and they cannot provide a primary outcome result where the endpoint was not measured.
General sample-size calculations depend on the outcome scale, variability, target effect, design, and analysis assumptions. A calculation for a comparison between two equally allocated arms does not match the recorded single-group design without a separate rationale. The registry record does not report the trial's own sample-size justification. Further, because no Ki67 levels were determined, there is no observed Ki67 effect in the posted results to interpret as a trial finding.
How should safety counts be interpreted?
Safety counts describe how many participants in the at-risk group were recorded as affected by the listed event category. They are not an efficacy comparison. The record reports 0 serious events among 5 at risk and 4 other events among 5 at risk. The registry does not list the serious-event terms, and deaths are not reported in the registry record. The labels do not identify the nature, timing, severity distribution, or relationship to treatment of the other events. Those details are not reported in the registry record.
In general, event counts need context, including the definition of each category, how events were collected, the observation period, and whether the count represents events or affected participants. No additional detail on these points is available in the registry record. The counts should therefore be read narrowly as the recorded figures for the stated at-risk group, without inferring unreported event characteristics.
What cannot be recovered from the record?
Statistical methods cannot reconstruct unavailable outcomes. There are no Ki67 measurements from which to estimate a mean change, assess variability, or examine individual responses. The record also does not report analyses for the listed secondary outcomes. The number of missing or unevaluable measurements, analysis populations, and methods for handling missing data are not reported in the registry record. These omissions prevent evaluation of analytic choices and leave no basis for sensitivity analyses.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures: the primary Ki67 change endpoint and secondary changes in circulating IGF-1 and IGFBP-3. It lists 0 analyses. No multiplicity strategy is reported in the registry record. In general, when several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for the family of tests. A prespecified approach can define which outcome is primary and how secondary results are interpreted. The record identifies a primary endpoint, but it does not describe a multiplicity adjustment or testing hierarchy.
No primary Ki67 measurements were determined. Results for the secondary biomarker outcomes are not reported in the registry record. Therefore, there are no posted outcome estimates or tests on which to assess multiplicity in practice. It would be inappropriate to infer either that a multiplicity adjustment was used or that all listed outcomes were analyzed.
The registry record does not report the analysis population, participant-level missingness, or methods for handling missing data. The statement that no Ki67 levels were determined indicates that the planned primary measurements are unavailable, but it does not specify whether any other measurements were collected. The record does not describe exclusions, imputation, or sensitivity analyses. Those methods are not reported in the registry record.
In general, missing-data methods rely on assumptions about why observations are unavailable. Those assumptions and the pattern of missingness can affect an estimate. When an endpoint has no reported measurements, statistical adjustment cannot create observed information about the endpoint. The available record does not support an assessment of missing-data assumptions or the consequences of any particular method.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Metformin | 0 | 5 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Metformin | 4 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Metformin |
|---|---|---|
| diarrhea | Gastrointestinal disorders | 4 of 5 |
| nausea | Gastrointestinal disorders | 2 of 5 |
| vomiting | Injury, poisoning and procedural complications | 1 of 5 |
| weight loss | Investigations | 1 of 5 |
The registry reports serious adverse events for the Metformin group with 5 at risk and 0 affected. For other adverse events, it reports 5 at risk and 4 affected. These are the posted counts for the recorded categories. Deaths are not reported in the registry record, and no top serious adverse-event terms are listed.
These figures should be interpreted as safety counts, not as evidence about the primary Ki67 endpoint. The registry record does not describe the specific other events, their severity, timing, duration, or relationship to treatment. It also does not provide additional detail about event collection or the observation period. Those details are not reported in the registry record.
In general, a count of affected participants does not summarize every aspect of safety. The kinds of events, their clinical features, and the completeness of reporting matter for a fuller assessment. The posted figures should therefore be read narrowly: the record reports no serious events in the stated at-risk group and reports other events affecting 4 participants in the stated at-risk group. The figures do not establish a treatment effect or explain the experience of individual participants.
12. What the Result Does, and Does Not, Mean
This record establishes that investigators planned a presurgical study of metformin hydrochloride in women with operable stage I or stage II breast cancer. The intended regimen was 850 mg orally twice daily for 7-21 days, stopping 24-36 hrs before surgery. The primary question concerned change in breast-tissue Ki67 levels between baseline and the period around surgery.
The record does not establish whether Ki67 changed. It explicitly states that no Ki67 levels were determined because the trial closed due to slow accrual. Accordingly, there is no reported primary endpoint estimate, no measure of its precision, and no statistical test to interpret. This is an unavailable outcome, not evidence of no change and not evidence of a change.
The single-group design also matters. There is no randomized comparison recorded, so the design was not set up to compare outcomes against a concurrent control group. General before-and-after observations can describe a pattern within a group, but they do not by themselves isolate a treatment effect. Here, no primary outcome measurements are reported in any case.
The registry also names secondary biomarker outcomes involving IGF-1 and IGFBP-3, but their results are not reported. The safety record reports 0 serious adverse events among 5 at risk and 4 other adverse events among 5 at risk; deaths are not reported in the registry record. These counts do not answer the biomarker question.
The trial's status and enrollment provide context for why the planned evidence is incomplete. The registry lists enrollment of 5 and says the study was terminated due to slow accrual. It does not report a trial-specific sample-size justification or an analysis plan. Planning illustrations based on assumptions about a two-arm comparison should not be mistaken for observed statistical power or for results from this single-group study.
The defensible conclusion is limited: the record documents an intended treatment schedule and biomarker question, but does not contain the primary outcome data needed to estimate change. It cannot support a conclusion about the direction, magnitude, or precision of the Ki67 response.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a clearly specified endpoint and an observed endpoint. The primary question was concrete: measure the percentage of Ki67-positive nuclei in breast tissue and determine a mean score before and after the presurgical treatment period. But the registry states that no Ki67 levels were determined. Without measurements, there is no effect estimate to interpret, regardless of how clearly the endpoint was planned.
The trial also highlights the limits of small, single-group studies. Enrollment was 5, and the registry records no randomized comparison. A single-group before-and-after design can describe change if measurements are available, but it cannot provide the same comparison as a randomized control group. In this record, the missing primary endpoint means even a descriptive change cannot be estimated.
Another statistical lesson is that planning assumptions and study findings serve different purposes. The record describes sample-size illustrations with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not establish the trial's own design rationale, and planning figures are not observed power. They cannot substitute for endpoint measurements.
Finally, the safety counts must remain separate from the unobserved efficacy endpoint. The record reports no serious adverse events in the at-risk group and reports other adverse events, but those figures do not answer whether Ki67 changed. A careful reading keeps each type of evidence within its scope and does not convert an incomplete outcome record into a positive or negative treatment finding.
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 central limitation is that the planned primary endpoint was not measured: the registry states that no Ki67 levels were determined. Consequently, there is no primary outcome estimate, uncertainty measure, or analysis to assess. The stated reason was closure due to slow accrual.
Enrollment was 5, and the study is recorded as single-group, with allocation NA and no randomized comparison. This limits the kind of comparison the design could support. The record does not report a concurrent control group, and a within-group pattern, even if available, would not by itself establish a causal treatment effect.
The registry lists secondary outcomes for circulating IGF-1 and IGFBP-3, but does not report their results. It lists 2 outcome measures and 0 analyses. The analysis population, endpoint-level missingness, missing-data methods, and sensitivity analyses are not reported in the registry record. It is therefore not possible to assess how incomplete data were handled or whether the secondary measurements were collected.
The safety information is limited to the posted counts. No top serious adverse-event terms are listed; deaths and the details of other events are not reported in the registry record. The event descriptions, timing, and other context are unavailable.
The registry record also does not report the trial's own sample-size justification or a statistical analysis plan. The described planning assumptions concern a two-arm illustration and should not be treated as an account of the completed single-group study's analysis. These limits leave the record informative about the intended study and its termination, but not about the primary biomarker outcome.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Metformin Hydrochloride in Treating Women With Stage I or Stage II Breast Cancer That Can Be Removed By Surgery — NCT00984490.
- Registry record last updated 2024-02-01; status last verified 2024-01.
- Results first posted 2012-07-13.
- 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.
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18. Record Summary
The record describes a phase I, single-group presurgical study of metformin hydrochloride in women with operable stage I or stage II breast cancer. The intended regimen was 850 mg orally twice daily for 7-21 days, stopped 24-36 hrs before surgery. The primary endpoint was change in breast-tissue Ki67 levels, assessed at baseline and between 8-23 days.
Enrollment was 5. The study is recorded as TERMINATED, with slow accrual given as the reason for closure. No Ki67 levels were determined. Secondary outcomes concerned circulating IGF-1 and IGFBP-3, but results are not reported in the registry record. The record lists 0 analyses.
Safety counts list 0 serious adverse events among 5 at risk and 4 other adverse events among 5 at risk. Deaths are not reported in the registry record. Overall, the registry documents the planned question and treatment but provides no primary biomarker result.