Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer. (NCT01703754), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase II, randomized, open-label study with a parallel design. The official title describes Ad-RTS-hIL-12 monotherapy or combination with palifosfamide in people with recurrent or metastatic breast cancer and accessible lesions. The arm descriptions name Ad-RTS-hIL-12 with veledimex as the experimental monotherapy arm and Ad-RTS-hIL-12 with palifosfamide as the combination-therapy arm. Masking is listed as none, so the record describes the study as open label.

The registry record gives enrollment as 12. The study started on 2013-04-04, and its primary completion date is 2014-08-07. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or what results were available at that time.

The brief summary describes a safety and efficacy study. It identifies progression-free survival at the 16 week treatment time point as the primary endpoint in that summary. The separate primary outcome description instead names the number of participants with TEAEs, with a timeframe of 16 months. These descriptions differ in outcome and timeframe. The registry record does not resolve that inconsistency or report a primary-endpoint result.

The interventions are listed as Ad-RTS-hIL-12 and veledimex, and palifosfamide. The safety results list three Ad-RTS-hIL-12 plus veledimex dose groups, while the arm descriptions name monotherapy and combination therapy. The record does not explain the relationship between these groupings. It also does not report details such as the randomization procedure, planned allocation, or the rationale for the enrollment target. Those design details should not be inferred from the general trial description.

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: Following the decision by the SRC the study will only collect data for the part 1, arm A group. Three dose level cohorts (140 mg, 100 mg, 80 mg) for INXN-1001 are used instead of the original single INXN-1001 dose level. Summaries that were based on part and treatment arm will instead be by dosage level of INXN-1001 where appropriate, with an overall group containing data from all dosage levels.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety population is defined as all subjects who receive at least one dose of study treatment (veledemix capsule and/or an injection of Ad-RTS-hIL-12).

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.

Population: The Safety population is defined as all subjects who receive at least one dose of study treatment (veledemix capsule and/or an injection of Ad-RTS-hIL-12).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over 16 months.

The primary outcome description names the number of participants with treatment-emergent adverse events (TEAEs), measured over 16 months. Its description says the measure captures TEAEs, serious adverse events (SAEs), and adverse events leading to discontinuation. The defined safety population includes participants who received at least one dose of study treatment, described as veledimex and/or an injection of Ad-RTS-hIL-12. The record says safety and tolerability were assessed through adverse-event monitoring, physical examinations, vital signs, electrocardiograms, and clinical laboratory evaluations.

In general, counting participants with an event gives a direct description of how many people in a defined population experienced an outcome. It is important to distinguish such a count from the number of events: a participant may experience more than one event, while a participant-based measure counts that person once for the specified outcome. The registry record does not give a result for the stated primary outcome, nor does it provide a complete TEAE summary by treatment arm.

The brief summary presents a different primary focus: progression-free survival at the 16 week treatment time point. In general, a time-to-event outcome describes the time until a specified event occurs, while a fixed-time measure can describe status at a chosen time point. The registry record does not provide a result for that progression-free survival description either. The differing outcome definitions and timeframes make it important to identify which measure is being discussed rather than treating the descriptions as interchangeable.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching each result to its outcome definition, population, timeframe, and analysis method. The registry record describes a randomized, open-label, parallel Phase II study, but provides no statistical analyses. The count of analyses is listed as 0. That means the record does not present an analyzed treatment comparison from which to assess an effect estimate, uncertainty, or statistical significance.

What does a participant count represent?

In general, a participant count for an adverse-event outcome records whether a person experienced the specified event during the defined observation period. It differs from an event count, because one person may have multiple events. The primary outcome description uses participant counts and defines a safety population based on receipt of at least one dose. The safety results additionally show participants at risk and affected in the listed groups. These measures should be read using their own stated definitions; they are not automatically interchangeable with the primary endpoint.

The record does not report a complete result for the primary TEAE outcome. It gives serious and other adverse-event counts by three dose groups, but does not state that these counts constitute the full primary-endpoint analysis. Nor does it supply a result for adverse events leading to discontinuation, which are mentioned in the outcome description. Without an outcome-level analysis and its denominator definitions, the counts cannot be used to reconstruct an overall primary-endpoint result.

How should uncertainty be understood?

In general, an estimate describes the observed data, while a confidence interval expresses the range of values compatible with the data under a statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, but does not by itself establish clinical importance or remove bias. The registry record does not report confidence intervals for the safety counts or treatment effects. The small enrollment listed in the record means the observed counts describe a limited study population; it does not permit a precise estimate of how often events would occur in other populations.

In general, comparisons between treatment groups require a defined contrast, an outcome measure, and an analysis that accounts for how the data were collected. Random allocation can reduce confounding on average, but it does not eliminate the need to report the actual group sizes, follow-up, missing observations, and analysis methods. This record does not report a treatment contrast, a p-value, or an estimate of uncertainty. Accordingly, the safety counts should not be treated as evidence of a statistically established difference between groups.

What does the trial structure imply?

A parallel design assigns participants to a treatment group and follows their outcomes in that group. In an open-label study, treatment assignment is not masked as described in the record. In general, lack of masking can influence reporting or assessment of outcomes, particularly when measurement involves judgment. The record does not state how outcome assessments were conducted or whether any protections against assessment bias were used. The endpoint description mentions monitoring procedures, but does not give details about adjudication or blinded assessment.

The registry record's arm descriptions identify monotherapy and combination therapy. The safety results, however, are organized into three veledimex dose groups, without a listed palifosfamide combination group in those results. The record does not explain the relationship between these descriptions. This makes it inappropriate to assume the safety groups map directly onto the named randomized arms or to infer an unreported combination-arm safety profile.

What can a planning calculation show?

In general, a sample-size calculation estimates how many participants would be needed under stated assumptions to detect a chosen effect with a chosen statistical procedure. The registry record's planning assumptions describe an illustration based on an observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation. They state that the effect to detect is a specified fraction of the observed effect. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect.

Planning illustrations are not observed power. Observed power is not a substitute for reporting the estimated effect and its uncertainty. A small or inconclusive study result should be interpreted through the estimate, interval, design, and completeness of follow-up, rather than a retrospective power calculation. In this record, no treatment-effect estimate or analysis is reported, and the primary outcome is flagged as having several categories or time points rather than being reduced to one comparison. The illustration therefore cannot supply an unreported efficacy result or establish what the study could reliably detect.

Why do outcome definitions matter?

The record lists 13 outcome measures, including best overall response by mRECIST v1.1, progression-free survival by modified RECIST v1.1, pharmacokinetic measurement of INXN-1001, immune response measures, serum markers, and T-cell counts. These outcomes represent different kinds of data and would not necessarily use the same statistical method. The registry record does not report results or analysis methods for them. In general, methods should fit the outcome's scale, follow-up structure, and missing-data pattern; a method suitable for a binary participant count may not suit a time-to-event outcome or a repeated laboratory measure.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures, including the primary outcome description and secondary measures for response, progression-free survival, pharmacokinetics, immune response, serum markers, and T-cell counts. When a study examines multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately. In general, a prespecified testing hierarchy or multiplicity adjustment can help control that risk. The record does not report a multiplicity strategy, a statistical analysis plan, or results for these outcomes. It is therefore not possible to determine which analyses, if any, were confirmatory.

Missing-data methods are also not reported in the registry record. The record does not describe the amount or pattern of missing outcome data, participant withdrawals, or how unavailable measurements were handled. In general, missingness can affect interpretation when participants with observed data differ from those without observed data. Without the extent of missingness and the analysis approach, the robustness of any outcome estimate cannot be assessed. No outcome estimates are posted from which to examine this issue directly.

The safety population is defined as all subjects who receive at least one dose of study treatment. The registry record does not give a corresponding efficacy-analysis population or explain whether all randomized participants were included in any efficacy analysis. It also does not report an intention-to-treat approach or other analysis-population rules. The primary outcome description and the brief summary give different primary outcomes and timeframes, and the record does not explain how that difference was handled analytically. These gaps limit assessment of whether the reported populations and methods align with the study questions.

11. 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: disease progression (100.0%), dyspnoea (100.0%), pyrexia (28.6%), cytokine release syndrome (25.0%), neutropenia (14.3%).

The serious adverse-event counts are reported by Ad-RTS-hIL-12 plus veledimex dose group. In the 140 mg group, 4 participants were affected among 7 at risk; in the 100 mg Daily group, 2 were affected among 4 at risk; and in the 80 mg Daily group, 1 was affected among 1 at risk. The other adverse-event counts are 7 among 7, 4 among 4, and 1 among 1, respectively. The deaths listed for these groups are 0, 0, and 1.

These counts are descriptive. The record does not report confidence intervals, a statistical comparison between groups, or the relationship of these dose groups to the named randomized arms. The listed percentages for serious-event terms—Disease progression and Dyspnoea at 100.0%, Pyrexia at 28.6%, Cytokine release syndrome at 25.0%, Neutropenia at 14.3%, and Superior vena cava syndrome at 14.3%—lack a stated denominator in the record. They should be read as reported term percentages, not assigned to a treatment group or interpreted as risks among all enrolled participants.

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

The registry record documents a randomized, open-label Phase II study of Ad-RTS-hIL-12 as monotherapy or in combination with palifosfamide in recurrent or metastatic breast cancer with accessible lesions. It also gives selected safety counts for Ad-RTS-hIL-12 plus veledimex dose groups. Those counts describe the participants and events recorded in those groups; they do not provide a comparative analysis or a complete account of the study's stated primary outcome.

The record does not report a result for the number of participants with TEAEs, despite describing that as the primary outcome over 16 months. The brief summary identifies progression-free survival at the 16 week treatment time point as primary, but no result for that measure is reported either. As a result, the posted record cannot establish a treatment effect on either of those outcomes. The discrepancy between the two primary-outcome descriptions is unresolved in the registry record.

The adverse-event counts do not by themselves determine whether one treatment group had a higher or lower underlying risk. The group sizes are limited, no uncertainty intervals or comparative analyses are reported, and the registry does not explain how the safety groups relate to the randomized arm descriptions. The serious-event term percentages also lack an accompanying denominator definition. These constraints prevent a reliable comparative interpretation of those figures.

In general, a trial's result is best understood through its prespecified outcome, the population analyzed, the effect estimate, its precision, and the completeness of follow-up. The record does not report those elements for an efficacy comparison, and lists 0 analyses. Its terminated status is a study-status fact, not an explanation of the termination or evidence for a particular outcome. The available information supports describing the trial's design and selected safety data, but not a conclusion that either treatment is effective, ineffective, safer, or less safe.

13. Why This Trial Matters Statistically

This study raises several statistical interpretation issues that matter when reading early-phase randomized trials. It was randomized and parallel, but open label, and the registry record does not describe the allocation procedure or outcome-assessment safeguards. Randomization is valuable for forming a comparative study, but meaningful interpretation also requires transparent reporting of how the randomization was implemented, which participants were analyzed, and how outcomes were measured.

The record uses two different descriptions of the primary outcome: a participant count for TEAEs over 16 months and progression-free survival at the 16 week treatment time point in the brief summary. Clear outcome definitions and timeframes are essential because they determine what data are collected and what analysis answers the trial question. The record does not reconcile these descriptions or report a result for either one.

The safety material also illustrates why denominators and grouping must be clear. Counts are presented for three dose groups, while the trial arms are described as monotherapy and combination therapy. Without an explanation linking those groupings, readers cannot safely interpret the dose-specific counts as a direct comparison of the randomized arms. Reported term percentages without stated denominators add another interpretive limitation.

The record lists multiple outcome measures but no analyses. In general, transparent reporting of analysis plans, multiplicity handling, missing data, and uncertainty allows readers to distinguish exploratory findings from confirmatory evidence. These elements are not reported. The resulting lesson is methodological: a trial's randomized design does not, on its own, replace the need for clear outcome definitions and complete analysis reporting. The record is informative about the planned study and selected safety counts, while leaving the primary comparative questions unanswered.

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.

Several limitations are specific to the registry record. The brief summary identifies progression-free survival at the 16 week treatment time point as the primary endpoint, while the primary outcome description identifies the number of participants with TEAEs over 16 months. The record does not explain this difference or report a result for either outcome. That makes it difficult to identify which primary question the posted results address.

The study is marked terminated, but the reason is not reported in the registry record. Enrollment is listed as 12, and no statistical analyses are listed. The record does not provide efficacy estimates, confidence intervals, p-values, or an account of the analysis populations. It also does not report the randomization procedure, allocation ratio, sample-size rationale, or analysis plan.

The safety results are organized into Ad-RTS-hIL-12 plus veledimex dose groups, whereas the arm descriptions distinguish monotherapy from combination therapy with palifosfamide. The record does not explain how these categories correspond. The serious-event term percentages are not accompanied by denominators, and the safety counts do not include a reported comparative analysis. Consequently, those figures should not be interpreted as complete arm-level comparative safety results.

Finally, the registry does not report missing-data handling, follow-up completeness, or results for the listed response, pharmacokinetic, and immune outcomes. The absence of these details prevents assessment of outcome precision and the extent to which the analyses, if any, represent all randomized participants. These are reporting limitations; the record does not establish why the information is absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer. — NCT01703754.
• Registry record last updated 2025-08-28; status last verified 2025-08.
• Results first posted 2025-08-28.
• 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.

18. Record Summary

NCT01703754 is a randomized, open-label Phase II study of Ad-RTS-hIL-12 monotherapy or combination with palifosfamide in recurrent or metastatic breast cancer with accessible lesions. The registry lists enrollment of 12, start date 2013-04-04, primary completion date 2014-08-07, and status as terminated.

The brief summary names progression-free survival at the 16 week treatment time point as primary, while the primary outcome description names participants with TEAEs over 16 months. No result for either description is reported, and the record lists 0 analyses. Selected safety counts are reported for three Ad-RTS-hIL-12 plus veledimex dose groups, but their relation to the named study arms is not explained. The record does not provide a comparative efficacy analysis or resolve the primary-outcome discrepancy.