Chemokine Modulation Therapy and Standard Chemotherapy Before Surgery for the Treatment of Early Stage Triple Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Chemokine Modulation Therapy and Standard Chemotherapy Before Surgery for the Treatment of Early Stage Triple Negative Breast Cancer (NCT04081389), a na phase 1 study. The primary outcome is Number of Patients With Dose Limiting Toxicities.

2. Clinical Question

The clinical question is therefore mainly about safety and dose finding, rather than whether this combination is more effective than another treatment. The trial enrolled 9 participants and is listed as phase I. It studied chemokine modulation with chemotherapy given before surgery for early-stage triple-negative breast cancer. Triple-negative disease is reflected in the listed estrogen receptor negative, progesterone receptor negative, and HER2/Neu negative conditions.

The registry also lists pathological complete response, residual cancer burden, recurrence-free survival, and overall survival as secondary outcomes. These outcomes describe tumor response and later clinical outcomes, but their results are not reported in the registry record. Without a randomized comparator, the study cannot establish a comparative treatment effect. Its small enrollment and dose-level structure also mean that the posted information should be read as an early safety and feasibility record, not as a definitive estimate of efficacy.

3. Trial Design

This is a phase I clinical trial sponsored by Roswell Park Cancer Institute. The registry lists the study as completed, with a start date of 2019-12-06 and a primary completion date of 2022-05-24. Enrollment was 9. The design is listed as single group, allocation as not applicable, and masking as none. These features indicate that the study was not organized as a randomized, masked comparison between separate treatment strategies.

The registry lists four dose-level arms, identified as interferon alpha-2b at DL 1, DL 2, DL 3, and DL 4. The primary endpoint description says dose-limiting toxicity information is used to identify an appropriate dose level of chemokine modulation therapy and paclitaxel for future clinical exploration. The registry does not report the dose-escalation rules or the full rationale for selecting the dose levels.

The interventions include celecoxib, recombinant interferon alfa-2b, rintatolimod, paclitaxel, doxorubicin, and cyclophosphamide. One arm description specifies celecoxib by mouth twice daily, interferon alfa-2b and rintatolimod intravenously on days 1-3 of weeks 1-3, and paclitaxel intravenously once weekly. It describes treatment continuing for 12 weeks in the absence of disease progression or unacceptable toxicity. The record’s arm title also mentions doxorubicin and cyclophosphamide, but the posted arm description does not state their administration schedule.

The study population and procedures are described in the registry, but full eligibility criteria, detailed dose-level schedules, and the statistical analysis plan are not reported in the registry record. Because there is no randomized control group, comparisons among dose-level arms should not be interpreted as controlled comparisons of treatment effectiveness. Differences between arms could reflect their small group sizes or other factors, and the registry record does not establish that the groups are comparable.

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:

Analysis population for the primary outcome, as defined in the registry: 1 patient was not DLT evaluable in DL3.

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 Number of Patients With Dose Limiting Toxicities, measured over Within 21 days of treatment adminstration.

The primary endpoint is the number of participants with dose-limiting toxicities. It is a count of participants experiencing qualifying toxicity, with a stated assessment window within 21 days of treatment administration. The endpoint description says safety and toxicity are assessed using the CTEP NCI Common Terminology Criteria for Adverse Events, version 5.0. It further says the resulting information is intended to help identify an appropriate dose level of chemokine modulation therapy and paclitaxel for future clinical exploration.

In general, a dose-limiting toxicity endpoint is used in early-phase research to identify clinically important tolerability concerns at a studied dose. It differs from an efficacy endpoint: its purpose is to characterize toxicity during a defined observation period, not to establish whether the treatment improves disease outcomes. The endpoint’s interpretation depends on how a qualifying toxicity is defined, whether it is judged related to study treatment, and which participants can be evaluated within the window.

The registry description includes criteria concerning timing and investigator attribution of toxicity to celecoxib, rintatolimod, interferon alfa-2b, or paclitaxel. However, the available description is truncated, and the complete DLT definition is not reported in the registry record. The primary endpoint count and its analysis are also not reported. The record notes that 1 patient was not DLT evaluable in DL3, but does not give the complete evaluable population or the observed DLT count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of statistical question is this?

This is a dose-finding safety question. The primary endpoint is a count of participants with dose-limiting toxicities during a defined period. In general, phase I studies use safety observations to inform later clinical exploration. The objective is different from testing whether a treatment is superior to a control. The registry record describes a single-group design and does not report a randomized comparator.

The endpoint is a binary event at the participant level: each participant is either counted as having a qualifying DLT or not, subject to being evaluable and meeting the registry’s definition. The number of participants with an event is a count. To interpret a count, readers also need to know the number assessed, the time window, the event definition, and how missing or unevaluable observations were handled. The record states that 1 patient was not DLT evaluable in DL3, but the complete endpoint count and analysis population are not reported in the registry record.

Why does the observation window matter?

The primary endpoint timeframe is within 21 days of treatment administration. In general, a fixed observation window makes clear which period contributes to an endpoint, but it also means events outside that window may not count toward that endpoint unless the protocol specifies otherwise. The registry’s endpoint description ties DLT assessment to the first dose of combination therapy and describes toxicity attribution. Its available text is incomplete, so the full operational definition, including all qualifying events, is not reported in the registry record.

The endpoint description names the CTEP NCI Common Terminology Criteria for Adverse Events, version 5.0, as the assessment framework. In general, standardized toxicity criteria help classify the type and severity of adverse events consistently. Classification still depends on the study’s rules for attribution, timing, and which events qualify as dose limiting. Those details are important because the count is only meaningful relative to the applied definition.

How should counts and uncertainty be understood?

General statistical context: an event count is descriptive, while an estimated event rate relates that count to the participants assessed. Uncertainty is usually greater when few participants contribute information. Confidence intervals can communicate that uncertainty, but the registry record does not report a confidence interval for the primary endpoint. A numerical interval should not be reconstructed without the underlying result and an explicit analysis method.

For a small dose-level study, each participant’s outcome can have a substantial influence on the apparent pattern. Counts across dose levels can help describe what was observed, but they do not by themselves establish a dose-response relationship. That interpretation would require a suitable analysis and detailed knowledge of how participants were assigned to dose levels, how escalation decisions were made, and how evaluability was defined. Those protocol and analysis details are not reported in the registry record.

What does the design imply for comparisons?

The registry lists a single-group model, allocation as not applicable, and no masking. The arms are distinguished by dose level, rather than being described as randomized treatment and control groups. General statistical context: randomization is used to reduce systematic differences between comparison groups, while masking can reduce certain forms of measurement or management bias. Without those features, descriptive differences between arms can be influenced by group composition, timing, and the study’s dose-level process.

Accordingly, the arm-specific adverse-event counts should not be treated as an unbiased comparison of treatment strategies. They can describe what was recorded within each listed arm. They cannot establish that a difference between arms was caused by dose level, especially when the groups are small and the registry does not report a comparative statistical analysis. The record lists 0 analyses, and inferential results for the outcomes are not reported.

What are the planning illustrations?

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect is a stated fraction of the observed effect. In general, such illustrations show how sample-size requirements depend on assumptions about the effect, variability, significance level, and desired power. They are not observed trial outcomes and are not observed power.

The described assumptions concern a hypothetical two-arm planning framework, whereas this trial is recorded as single group with dose-level arms and no randomized control comparison. The registry does not report the trial’s own sample-size justification or analysis plan. Therefore, a planning illustration should not be mistaken for a design feature of this study or evidence about its achieved precision. The registry entries do not include numerical planning outputs or a numerical observed effect to interpret.

What can be inferred from the posted analyses?

The registry lists five outcome measures and no analyses. It therefore does not present an inferential analysis of the primary endpoint or the listed secondary outcomes. In general, a p-value assesses compatibility between data and a specified statistical model under a null hypothesis; it does not measure clinical importance or eliminate bias. A confidence interval conveys estimation uncertainty under a model. Neither can be interpreted for this trial’s primary endpoint from the record because corresponding estimates are not reported.

The appropriate statistical reading is consequently limited: identify the endpoint and its observation window, recognize the small phase I single-group design, and treat the reported event counts as descriptive. The DLT result, uncertainty around that result, and the analysis population beyond the noted unevaluable participant are not reported in the registry record.

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("Arm 1: Interferon Alpha-2b at DL 1", "Arm 2: Interferon Alpha-2b at DL 2", "Arm 3: Interferon Alpha-2b at DL 3", "Arm 4: Interferon Alpha-2b at DL 4")
n      <- c(1, 1, 3, 3)
events <- c(0, 0, 0, 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  Arm 1: Interferon Alpha-2b at DL 1  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Arm 2: Interferon Alpha-2b at DL 2  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Arm 3: Interferon Alpha-2b at DL 3  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Arm 4: Interferon Alpha-2b at DL 4  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, the number of participants with dose-limiting toxicities, and secondary outcomes that include pathological complete response, residual cancer burden, recurrence-free survival, and overall survival. It does not report an analysis plan addressing multiplicity, such as whether or how testing across multiple outcomes was controlled. The results and statistical analyses for these outcomes are not reported in the registry record.

In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. If many tests are conducted, the chance of at least one apparently notable result can increase. A prespecified hierarchy or adjustment can help manage that issue, but the registry does not report whether such procedures were planned. No inferential results are available to assess the practical impact of multiplicity in this study.

The record notes that 1 patient was not DLT evaluable in DL3. It does not report the full number of participants evaluable for the primary endpoint, the reasons for unevaluability, how missing endpoint observations were handled, or whether any participants were excluded from other outcome analyses. The analysis populations for the secondary outcomes are not reported in the registry record.

General statistical context: missing outcome data can affect interpretation when the probability of missingness is related to a participant’s health or observed outcome. Transparent reporting usually identifies the analysis population, reasons for missing data, and any assumptions or methods used to address them. Those details cannot be assessed from the registry information available. The posted record therefore does not establish whether all enrolled participants contributed to each outcome or how incomplete follow-up was treated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lung infection (33.3%).

The registry reports adverse-event information separately for four arms: interferon alpha-2b at DL 1, DL 2, DL 3, and DL 4. For serious adverse events, it lists participants at risk and participants affected. The corresponding counts are 1 and 0 for DL 1, 1 and 0 for DL 2, 4 and 1 for DL 3, and 3 and 1 for DL 4. These are descriptive counts within the listed arms.

For other adverse events, the listed at-risk and affected counts are 1 and 1 for DL 1, 1 and 1 for DL 2, 4 and 4 for DL 3, and 3 and 3 for DL 4. The deaths field lists 1 for DL 1, 0 for DL 2, 1 for DL 3, and 0 for DL 4. The registry does not provide enough information in these figures to determine the cause of death or whether a death was considered related to treatment. The observation period and detailed event definitions for these adverse-event counts are not reported in the registry record.

The registry identifies lung infection as the top serious adverse event term at 33.3%. That percentage should not be read as a dose-limiting toxicity rate: the relationship between the term, the DLT definition, and the endpoint count is not reported. Small group counts also make direct comparisons unstable. These figures describe recorded safety events; they do not establish that the dose levels differ in safety.

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

The central statistical meaning of this record is that the trial was designed as an early-phase safety and dose-finding study of chemokine modulation combined with chemotherapy before surgery. The primary endpoint asks how many participants experienced dose-limiting toxicities within the stated timeframe. The registry describes why that information matters for future clinical exploration, but the observed primary endpoint result is not reported in the registry record.

The posted adverse-event figures provide descriptive counts across four dose-level arms. They are useful for understanding what the registry records as having occurred, but the small group sizes and nonrandomized single-group design limit comparative interpretation. The counts do not show that one arm is safer than another, and the listed deaths cannot be attributed to treatment based on the information reported.

The record also lists tumor response and survival outcomes, including pathological complete response, residual cancer burden, recurrence-free survival, and overall survival. Their results are not reported. Therefore, the registry information does not establish the magnitude or precision of any response or survival outcome. It also does not provide a controlled estimate of the effect of the treatment combination.

General statistical context: an uncontrolled study can provide early descriptive information and guide questions for later research, but it cannot separate treatment effects from other possible explanations as effectively as a well-designed randomized comparison. Statistical precision is also constrained when few participants contribute data. A planning illustration, if consulted, represents assumptions for future sample-size planning, not observed power and not evidence that this study had adequate power for a treatment comparison.

The appropriate conclusion is limited to the design and recorded observations: this was a completed phase I single-group trial with enrollment of 9, a DLT-focused primary question, and reported adverse-event counts. The registry record does not report the primary endpoint result, its uncertainty, the full analysis population, or results for the listed secondary outcomes. Those gaps prevent a quantitative judgment about the study’s DLT frequency or clinical outcomes.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between dose finding and treatment-effect evaluation. A phase I trial can organize observations around toxicity and dose levels, while a later comparative study may ask whether a treatment changes clinical outcomes relative to another strategy. The registry’s primary endpoint is a DLT count, and its description connects that information to identifying a dose level for future clinical exploration. That is a different question from whether the combination improves tumor response or survival.

The design matters for interpretation. A single-group study with dose-level arms can describe what happened among participants treated in each arm, but it does not create randomized control groups. Statistical comparisons across those arms may be confounded by how dose levels were selected or by differences in the participants observed. The registry record does not report the allocation or escalation procedures in sufficient detail to support stronger comparisons.

The study also illustrates why endpoint reporting must include both an event count and a clear analysis population. The registry notes that 1 patient was not DLT evaluable in DL3, but the primary endpoint result and complete evaluability information are not reported. Without these details, readers cannot determine the observed DLT frequency or how precisely it was estimated.

General statistical context: early studies often have limited precision because relatively few participants contribute information. Such results can still help characterize what was observed and inform subsequent research, but they should not be treated as definitive efficacy evidence. This distinction is especially important when a registry lists secondary outcomes but does not post their results or analyses.

The statistical value of the record is therefore in clarifying the study’s safety question, design, and limits. It shows why dose-level observations, adverse-event definitions, missing endpoint data, and analysis populations must be reported clearly. The absence of a posted primary result makes it impossible to quantify the main endpoint from this registry record, regardless of the study’s completion status.

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 registry identifies a completed study and enrollment of 9, but the primary endpoint result is not reported. This is the most direct limitation for interpreting the study’s stated safety question. The note that 1 patient was not DLT evaluable in DL3 does not supply the DLT count among evaluable participants or the complete endpoint denominator.

The study is described as single group, with allocation not applicable and no masking. Its arms are listed by dose level, rather than as randomized treatment and control groups. Accordingly, arm-level differences in adverse-event counts cannot establish comparative safety or treatment effects. The small numbers within the listed arms also limit the precision of descriptive comparisons.

The full DLT definition is not available in the registry record: the endpoint description is truncated. Although it names the toxicity grading framework and includes timing and attribution criteria, the complete list of qualifying events cannot be assessed. The adverse-event record also does not state the observation period or complete event definitions for the reported counts.

Eligibility details, dose-level procedures, the trial’s sample-size justification, and its statistical analysis plan are not reported in the registry record. The complete analysis populations and handling of missing data are also not reported. Only 1 unevaluable participant is specifically noted, in DL3, without further explanation.

The registry lists secondary response and survival outcomes, but does not report their results or analyses. It also does not report confidence intervals or other inferential estimates for the primary endpoint. These omissions prevent assessment of precision, outcome completeness, and the statistical methods used. The information supports a description of the design and recorded safety counts, but not a quantitative conclusion about the primary endpoint or efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Chemokine Modulation Therapy and Standard Chemotherapy Before Surgery for the Treatment of Early Stage Triple Negative Breast Cancer — NCT04081389.
• Registry record last updated 2023-09-11; status last verified 2023-08.
• Results first posted 2023-09-11.
• 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

NCT04081389 is a completed phase I, single-group study sponsored by Roswell Park Cancer Institute. It enrolled 9 participants with early-stage triple-negative breast cancer and studied chemokine modulation therapy with chemotherapy before surgery. The registry lists four interferon alpha-2b dose-level arms and describes the primary endpoint as the number of participants with dose-limiting toxicities within 21 days of treatment administration.

The endpoint description names the CTEP NCI Common Terminology Criteria for Adverse Events, version 5.0, and says DLT information is intended to guide future dose-level exploration. The registry notes that 1 patient was not DLT evaluable in DL3. It also lists serious and other adverse-event counts and deaths by arm.

The primary endpoint result, complete analysis populations, and results for the listed secondary outcomes are not reported in the registry record. Because the trial is not a randomized comparison, its arm-specific counts are descriptive and do not establish comparative treatment effects.