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 Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer (NCT02768701), a na phase 2 study. The primary outcome is Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02768701 |
| Phase | Phase 2 |
| Condition | Triple Negative Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UNC Lineberger Comprehensive Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with metastatic triple-negative breast cancer who had received at least one prior line of therapy. The primary-outcome description identifies the population for that measure as subjects who received two doses of the study treatment. The registry record does not provide further details about participant characteristics or eligibility criteria.
Intervention
The single study group received cyclophosphamide and pembrolizumab. The arm description specifies a single dose of cyclophosphamide (300 mg/m2) given the day before cycle 1 of pembrolizumab (200 mg), with pembrolizumab administered every 3 weeks.
Comparator
There was no separate comparator group. The registry lists a single-group study and no allocation to a control arm. Consequently, the study does not provide a randomized, like-for-like comparison of the regimen against another treatment or against no treatment.
Primary question
The primary outcome was the change in regulatory T cells (Tregs) during study treatment, expressed as percent change. Tregs were counted from blood samples before treatment began and during treatment. The registry specifies a median and full range over a timeframe of up to 2 years, but the observed value and range are not reported in the registry record. The question is therefore framed by the registered measurement plan, rather than by a numerical primary-outcome result.
3. Trial Design
This was a Phase II, completed, single-group study sponsored by UNC Lineberger Comprehensive Cancer Center. The registry lists an enrollment of 40 and describes the condition as triple-negative breast cancer. The brief summary focuses on patients with metastatic disease who had received at least one prior line of therapy.
The intervention combined a single dose of cyclophosphamide with pembrolizumab. According to the arm description, cyclophosphamide (300 mg/m2) was given the day before cycle 1 of pembrolizumab (200 mg), which was administered every 3 weeks. The record names both drugs as interventions and lists one experimental arm.
Allocation is listed as not applicable, masking as none, and the model as single group. These design features mean the study does not set up a randomized comparison between groups, and the registry cautions that its arms are not a like-for-like control comparison. The results can describe outcomes observed in the study group, but the design does not isolate the regimen’s effect relative to a concurrent control.
The registry lists the start date as 2016-10-18, the primary completion date as 2022-05-01, and the status as completed. The primary outcome concerns percent change in Tregs, summarized by the median and full range over up to 2 years. Listed secondary outcomes are overall response rate, duration of response, disease control rate, overall survival, and treatment-associated toxicity. Although the record lists seven outcome measures, it contains no analysis entries. The primary outcome’s numerical result 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: A total of forty-nine subjects consented to the study, but eight were deemed to be ineligible and one subject has withdrawn the consent during screening. Forty subjects were enrolled and evaluable for toxicity and survival, and 39 subjects were evaluable for response.
Overall Study
| Stage | Experimental: Single Arm |
|---|---|
| STARTED | 40 |
| COMPLETED | 32 |
| NOT COMPLETED | 8 |
Analysis population for the primary outcome, as defined in the registry: The subjects received at least one dose of the study treatment were included.
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 | Experimental: Single Arm |
|---|---|---|
| Participants analysed | 40 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 32 |
| Age, Categorical: >=65 years | Participants | 8 |
| Sex: Female, Male: Female | Participants | 40 |
| Sex: Female, Male: Male | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 |
| Race (NIH/OMB): White | Participants | 28 |
| Race (NIH/OMB): More than one race | Participants | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 3 |
| Region of Enrollment: United States | participants | 40 |
| ECOG performance status: 0 | Participants | 24 |
| ECOG performance status: 1 | Participants | 16 |
| Stage at diagnosis: 0-III | Participants | 30 |
| Stage at diagnosis: IV | Participants | 10 |
| Prior (neo)adjuvant therapy: Yes | Participants | 33 |
| Prior (neo)adjuvant therapy: No | Participants | 7 |
| Sites of metastatic disease: Liver | Participants | 12 |
| Sites of metastatic disease: Lung | Participants | 14 |
| Sites of metastatic disease: Bone | Participants | 18 |
| Sites of metastatic disease: Lymph node | Participants | 4 |
| Sites of metastatic disease: Brain | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment., measured over Up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Percent Change in Tregs |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the change in regulatory T cells (Tregs) during study treatment, expressed as percent change. The registry describes counting Tregs in blood samples before treatment starts and during treatment, with a timeframe of up to 2 years. It specifies the median as the summary measure and the full range as the accompanying description of spread. The stated population for this outcome is subjects who received two doses of the study treatment.
Biological measurements can help characterize changes observed during treatment, rather than relying only on clinical outcomes such as response or survival. In general, a median describes the middle of a set of observations, while a full range describes the span from the lowest to the highest observed value. Those summaries can convey both a typical observed change and how widely individual measurements varied, but they do not show the full shape of the data distribution.
The registry does not report the median percent change or its range. It also does not give further detail about the timing of blood collections, the calculation of percent change, or how incomplete measurements were handled. Without the observed endpoint value and its analysis details, the registered measure identifies what was intended to be assessed, but does not establish the size or precision of the observed Treg change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed, single-group Phase II study and identifies a biological primary outcome: percent change in Tregs during treatment. It specifies that the median and full range were to summarize the outcome over up to 2 years. However, the numerical primary-outcome result is not reported in the registry record. Thus, the record identifies the intended endpoint but does not show the observed median change, the range, or the precision of an estimate.
The listed secondary outcomes cover response, duration of response, disease control, overall survival, and treatment-associated toxicity. The record lists seven outcome measures, but no analysis entries. The presence of named outcomes alone does not establish that numerical results, uncertainty estimates, or adjusted analyses are available in the record. If a result is not stated, its direction and magnitude cannot be inferred from the outcome label, the study status, or the fact that participants received treatment.
The single-group design is important for interpretation. Without a concurrent comparator, observed outcomes describe participants in the study group; they do not provide a randomized contrast with another treatment. Changes during treatment can be documented, but the design does not by itself distinguish the contribution of the study regimen from other explanations for changes. The registry specifically notes that the arms are not a like-for-like control comparison.
The adverse-event summary reports 18 participants affected among 40 at risk for serious events, 40 among 40 at risk for other events, and 5 deaths. These are registry summaries, not evidence by themselves that an event was caused by treatment. The record also lists several serious-event terms with percentages. Those entries describe reported safety information, but the absence of a comparator and the limited information about event attribution and follow-up restrict comparative interpretation.
Planning illustrations based on an observed effect, if consulted, should not be treated as observed power or as the study’s original design justification. The registry’s stated assumptions describe an illustrative calculation, not a trial-specific prospective sample-size plan. The record does not report the protocol’s sample-size justification, interim analyses, or a detailed statistical analysis plan. Overall, the available record supports a description of the design, registered outcomes, and safety summaries, but not a numerical conclusion about the primary endpoint or a controlled estimate of treatment effect.
9. Statistical Methods Explained
The registry describes a single-group study, with allocation listed as not applicable and masking as none. In a randomized comparison, allocation helps make groups comparable on average, and the contrast between groups can support an estimate of the difference associated with assigned treatments. This study has no such randomized control comparison. Its observations therefore describe the study group, rather than a treatment contrast against another group.
What does the primary summary measure?
The primary outcome is percent change in Tregs. The record says Tregs were counted in blood samples before treatment and during treatment, and specifies a median with a full range over up to 2 years. In general, the median is a measure of central location that is less affected by extreme values than the mean. The full range gives the lowest and highest observed values, but does not show whether observations cluster near the middle or are spread unevenly across the range. Neither summary replaces a confidence interval: a confidence interval is a statistical range intended to express uncertainty about an estimated quantity. No confidence interval for the primary outcome is reported in the registry record.
What would an analysis need to clarify?
Interpretation of a change measure depends on how the change was calculated, which follow-up observations contributed, and how missing measurements were handled. The registry notes measurements before treatment and during treatment, but does not report the calculation details or the analysis method. It also does not state whether the primary summary used every available observation, a defined follow-up visit, or a model incorporating repeated measurements. These details are not reported in the registry record, so the registered endpoint should not be read as a complete analysis specification.
Repeated measurements can be useful because they describe how an outcome changes over time. General statistical methods for repeated measurements need to account for the fact that observations from the same participant may be related. Treating related observations as if they were independent can make uncertainty estimates misleading. The registry does not identify a repeated-measures model or state how within-participant dependence was handled.
How should planning calculations be read?
The record’s planning assumptions describe an illustration computed from an observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record says time-to-event illustrations give the total number of events, while other illustrations give participants per arm. These assumptions describe the calculation framework; they do not turn this single-group study into a two-arm randomized trial.
In general, a sample-size calculation estimates how much information a future study might need under stated assumptions. A planning illustration based on an observed effect is sensitive to that effect estimate and to the assumed design. It is not observed power, does not show that the current study was adequately powered, and is not evidence that the study was originally designed around those assumptions. The registry does not report its own sample-size justification. The record also does not provide the numerical effect estimate needed to assess the planning illustration independently.
What can significance tests and uncertainty say?
A statistical test evaluates how compatible data are with a specified null hypothesis under a model. A p-value is not the probability that the null hypothesis is true, nor does it measure the clinical importance of a result. Confidence intervals are useful alongside tests because they show a range of values compatible with the data under the analysis assumptions. No primary-outcome test, p-value, or confidence interval is reported in the registry record. With no analysis entries, those inferential quantities cannot be interpreted from the registry information.
General methods also rely on assumptions about the data and analysis population. For example, over-dispersion occurs when variability is greater than a model expects; ignoring it can make standard errors too small and results appear more precise than warranted. This is a general consideration, not a reported feature of this study. The record does not specify whether over-dispersion was assessed or whether a model requiring such an assessment was used.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures, including the primary Treg measure and secondary outcomes concerning response, response duration, disease control, survival, and treatment-associated toxicity. When a study assesses multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. General approaches to multiplicity include identifying a primary comparison in advance, using a testing hierarchy, or adjusting inference across a defined family of tests. The record does not report a multiplicity strategy or specify how the listed outcomes were prioritized for statistical testing.
The registry lists no analysis entries. It does not report which outcomes were analyzed, whether subgroup or repeated-measures analyses were conducted, or whether any adjustment for multiple testing was applied. It would therefore be inappropriate to infer that multiplicity was controlled, or that every listed outcome has a reported result. The numerical primary endpoint result is not reported in the registry record.
Missing data can affect both the estimate and its precision, particularly when participants have measurements at some visits but not others. In general, an analysis should state how it defines the analysis population, handles unavailable measurements, and assesses whether missingness could influence conclusions. The registry does not report a missing-data method, the number of participants contributing measurements to the primary endpoint, or an analysis-population definition beyond identifying the primary-outcome population as subjects who received two doses of study treatment.
These omissions matter because a registered endpoint and a completed study do not, by themselves, reveal which observations entered an analysis or how uncertainty was handled. Details about prespecification, outcome reporting, missingness, and analysis populations are not reported in the registry record.
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 |
|---|---|---|---|
| Experimental: Single Arm | 18 | 40 | 45.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Experimental: Single Arm | 5 of 40 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Experimental: Single Arm | 40 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Experimental: Single Arm |
|---|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 3 of 40 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 40 |
| Abdominal pain | Gastrointestinal disorders | 2 of 40 |
| Sepsis | Infections and infestations | 2 of 40 |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | 2 of 40 |
| Anemia | Blood and lymphatic system disorders | 1 of 40 |
| Pericardial tamponade | Cardiac disorders | 1 of 40 |
| Myocardial infarction | Cardiac disorders | 1 of 40 |
| Supraventricular tachycardia | Cardiac disorders | 1 of 40 |
| Vomiting | Gastrointestinal disorders | 1 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Experimental: Single Arm |
|---|---|---|
| Fatigue | General disorders | 30 of 40 |
| Anemia | Blood and lymphatic system disorders | 28 of 40 |
| Lymphocyte count decreased | Investigations | 25 of 40 |
| Constipation | Gastrointestinal disorders | 21 of 40 |
| Nausea | Gastrointestinal disorders | 20 of 40 |
| Aspartate aminotransferase increased | Investigations | 17 of 40 |
| Peripheral sensory neuropathy | Nervous system disorders | 17 of 40 |
| Anxiety | Psychiatric disorders | 17 of 40 |
| Insomnia | Psychiatric disorders | 17 of 40 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 17 of 40 |
Serious events with the highest arm-level rate: neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, specify (7.5%), dyspnea (7.5%), abdominal pain (5.0%), sepsis (5.0%), generalized muscle weakness (5.0%).
The adverse-event summary lists 40 participants at risk for serious events, with 18 affected, and 40 at risk for other events, with 40 affected. It also lists 5 deaths. These are counts recorded for the single experimental group; they are not comparisons between treatment and control groups. The record does not establish from these counts alone that an event or death was caused by study treatment.
The listed serious-event terms include neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify and dyspnea, each reported as 7.5%; abdominal pain and sepsis, each reported as 5.0%; and generalized muscle weakness and anemia, reported as 5.0% and 2.5%, respectively. The percentages are registry entries for those terms. They should not be interpreted as comparative risks or as estimates of excess risk attributable to the regimen.
In general, adverse-event summaries depend on how events are defined, collected, coded, and followed. The registry record does not provide enough detail to infer event duration, severity beyond the serious-event classification, timing, or causal attribution for each listed term. With no concurrent control group, these figures describe reported events in the study group and cannot establish how they compare with another treatment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed Phase II study evaluated a single-group regimen of cyclophosphamide and pembrolizumab in patients with metastatic triple-negative breast cancer who had received at least one prior line of therapy. It also identifies the primary outcome as percent change in Tregs, with the median and full range specified as summaries. These details describe the study question and design.
The record does not report the numerical primary-outcome result. It therefore does not show the observed Treg change, the extent of variation, or the precision of the estimate. The listed response, survival, and toxicity outcomes do not supply a substitute for that missing primary result, and the record contains no analysis entries. Without numerical results and analysis details, the registered endpoint cannot support a conclusion about the magnitude or direction of the observed change.
The single-group design also limits what can be attributed to the regimen. Outcomes observed in participants can be described, but they are not a randomized comparison against a control. The record itself cautions that the arms are not a like-for-like control comparison. Thus, the design does not isolate a treatment effect from other potential influences on outcomes.
The safety summary provides counts and reported serious-event terms for the study group, including deaths. Those figures are descriptive. They do not, on their own, establish treatment causation or provide a comparative safety estimate. More detail about event attribution and the analysis is not reported in the registry record.
In general, statistical conclusions depend on the data, the analysis method, and the assumptions used to quantify uncertainty. The registry does not report the primary endpoint’s numerical estimate, an uncertainty interval, or a detailed statistical analysis plan. The appropriate interpretation is therefore limited to the registered design and outcome definitions, together with the safety summaries that are recorded; stronger claims about efficacy, comparative effect, or precision are not supported by the registry information.
13. Why This Trial Matters Statistically
This study illustrates the difference between a registered outcome and a reported statistical result. The record defines a biological primary endpoint, identifies its summary as the median and full range, and gives the measurement timeframe. Yet the numerical outcome is not reported in the registry record. Without that result, readers cannot assess the observed change or its variability, even though the endpoint itself is clearly named.
The single-group design is another central statistical feature. It permits description of outcomes among participants in the study group, but does not provide a randomized control comparison. This distinction matters when interpreting changes during treatment: observation over time is not the same as estimating a controlled treatment effect. The registry’s own note that arms are not a like-for-like control comparison reinforces that limitation.
The record also lists multiple outcome measures but no analysis entries. That makes it important to distinguish planned outcomes from analyzed and reported results. Multiplicity, missing data, analysis populations, and uncertainty methods can all affect how results should be read, yet these details are not reported in the registry record.
Finally, planning illustrations based on an observed effect have a different role from a prospective design justification. They depend on stated assumptions and should not be mistaken for observed power or evidence that the original study had a particular sample-size plan. Taken together, the record offers useful information about design, endpoint definition, and safety reporting, while also demonstrating why statistical interpretation depends on transparent outcome results and analysis methods.
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 most direct limitation of the registry information is that it does not report the numerical primary outcome, despite specifying the Treg measure and its intended summary. No estimate of the median percent change, full range, or confidence interval is available in the registry record. The record also lists no analysis entries, so it does not show how the endpoint was analyzed or what results were obtained for the listed secondary outcomes.
The single-group design has no randomized control group. Accordingly, the study does not provide a like-for-like treatment comparison, and the observed outcomes cannot be interpreted as a controlled estimate of treatment effect. The registry explicitly identifies the absence of a randomized comparison as a design limitation.
Important analysis details are not reported in the registry record. These include the statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, handling of missing measurements, and a detailed definition of analysis populations. The primary-outcome description identifies subjects who received two doses of study treatment, but does not provide further information about who contributed measurements or how incomplete follow-up was handled.
The safety summary is also descriptive rather than comparative. The record gives affected counts, deaths, and selected serious-event terms, but does not provide enough detail to establish causal attribution or compare rates with another group. Finally, planning illustrations based on an observed effect are not the trial’s own design justification. These limitations constrain what can be concluded from the registry record, especially about precision, comparative effects, and the interpretation of missing or unreported outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer — NCT02768701.
- Registry record last updated 2023-05-22; status last verified 2023-05.
- Results first posted 2022-08-03.
- 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 registry describes a completed Phase II, single-group study sponsored by UNC Lineberger Comprehensive Cancer Center, with enrollment listed as 40. It evaluated a single dose of cyclophosphamide followed by pembrolizumab administered every 3 weeks in patients with metastatic triple-negative breast cancer who had received at least one prior line of therapy.
The primary outcome was percent change in Tregs, summarized by the median and full range over up to 2 years. Secondary outcomes included response, response duration, disease control, overall survival, and treatment-associated toxicity. The registry lists seven outcome measures but no analysis entries; the numerical primary result is not reported in the registry record.
The adverse-event summary records 18 participants affected among 40 at risk for serious events, 40 among 40 at risk for other events, and 5 deaths. The single-group design provides no randomized control comparison, so the listed outcomes and safety information are descriptive rather than comparative.