Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer (NCT02047500), a na phase 1 study. The primary outcome is Number of Subjects Experiencing Dose Limiting Toxicity (DLT).

2. Clinical Question

The clinical question concerned safety and tolerability during dose escalation of TH-302 given with gemcitabine and nab-paclitaxel. The trial also sought to identify a recommended Phase 2 dose. Its primary endpoint was the number of participants experiencing a dose-limiting toxicity (DLT) up to Day 28 of Cycle 1. This is an early-phase safety question, not a randomized comparison of the combination with another treatment.

The registry also lists progression-free survival, objective response, duration of overall response, disease control, tumor metabolic response, and treatment-emergent adverse events among the secondary outcomes. These outcomes broaden the clinical description, but the record does not report numerical results for them in the information available for this analysis. They do not change the primary question’s focus on early safety and dose selection.

3. Trial Design

This was a multicenter, open-label, Phase I dose-escalation trial of TH-302 combined with gemcitabine and nab-paclitaxel. Its stated purpose was to evaluate safety, tolerability, and the recommended Phase 2 dose in previously untreated subjects with metastatic or locally advanced unresectable pancreatic adenocarcinoma. The record classifies the study as single-group and lists no masking. Enrollment was 19.

The treatment group is described as receiving the three-drug combination. The registry does not describe a separate control arm, and allocation is listed as not applicable. Consequently, the design does not support a like-for-like comparison between randomized groups. Dose escalation is part of the stated design, but the dose levels, escalation rules, decision thresholds, and dose-specific enrollment are not reported in the registry record.

The primary endpoint was the number of subjects experiencing DLT, assessed up to Day 28 of Cycle 1. The endpoint description notes that one patient was not evaluable because they did not complete Cycle 1. The record does not report the number of DLTs or explain how that participant was handled in any endpoint analysis.

The study started in 2014-01, had a primary completion date of 2015-09, and is listed as terminated. The reason for termination is not reported in the registry record. Although the listed secondary outcomes include time-to-event, response, metabolic, and safety measures, the registry record does not provide their numerical results in the information available for this analysis. The planned sample-size justification, dose-escalation protocol, and statistical analysis plan are also 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: One patient not evaluable as they did not complete cycle 1

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 Subjects Experiencing Dose Limiting Toxicity (DLT), measured over Up to Day 28 of Cycle 1.

The primary endpoint is the number of subjects experiencing dose-limiting toxicity (DLT) up to Day 28 of Cycle 1. It is a count endpoint: the intended summary is how many participants had the specified event during the stated assessment period. The record does not give a numerical count, a proportion, or an uncertainty interval for this endpoint.

In general, an early-cycle DLT endpoint is used in dose-escalation studies to identify toxicities that arise soon after treatment begins and to inform dose selection. This makes it relevant to the stated goal of determining a recommended Phase 2 dose. The endpoint’s interpretation depends on how a DLT is defined, which assessment rules are applied, and how participants who cannot complete the assessment period are handled. Those details are not reported in the registry record.

The record notes that one patient was not evaluable because they did not complete Cycle 1. It does not specify whether that participant was excluded, counted in another category, or included in a particular analysis population. The actual endpoint result and the analysis handling are therefore not available for interpretation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation is constrained by the available registry information. The study is recorded as Phase I, single-group, open-label, and dose-escalation. Enrollment was 19, and the primary endpoint is a count of participants experiencing DLT through Day 28 of Cycle 1. The record does not report a numeric outcome estimate or a statistical analysis plan. The explanations below give general statistical context and distinguish it from what is recorded for this trial.

What does a count endpoint tell us?

As general statistical context, a count endpoint records how many participants experienced a defined event. A count alone does not describe the event frequency unless the relevant denominator and analysis population are also clear. For a count of participants with an event, the definition of the event, the observation period, and the rules for participants with incomplete follow-up all affect interpretation.

For this trial, the stated event is DLT, the assessment period is up to Day 28 of Cycle 1, and the endpoint unit is participants. The registry notes one patient was not evaluable because they did not complete Cycle 1. It does not report the endpoint count, an analysis denominator, the DLT definition, or the handling of that participant. No rate should be reconstructed from enrollment alone.

Why is the design important?

As general statistical context, a single-group study can describe outcomes among participants receiving a regimen, but it does not create a contemporaneous randomized control group. Without that comparison, observed events cannot be separated statistically into treatment-associated effects and events that might also occur because of the underlying disease, other care, or chance. Open-label status means masking was not used, as recorded in the registry; the record does not describe any blinded outcome assessment.

Dose escalation adds another consideration. In general, dose-finding decisions depend on the dose levels tested, the number of participants assessed at each level, the DLT definition, and prespecified rules for changing or selecting a dose. The registry record does not report these details. It states that the trial aimed to identify a recommended Phase 2 dose, but the dose-specific outcomes and selected dose are not reported in the registry record.

How should uncertainty be understood?

As general statistical context, a confidence interval is a range of values compatible with the observed data under a specified statistical model. For a safety count or rate, an interval can communicate the uncertainty associated with a limited number of observed participants. The width and interpretation depend on the data and method. No confidence interval for the primary endpoint is reported in the registry record, so the precision of that endpoint cannot be evaluated.

A p-value, in general, measures how unusual the observed data would be under a specified null hypothesis and model. It does not by itself measure clinical importance, establish causation, or show that a result is precisely estimated. The registry record does not report a primary endpoint p-value or a formal comparison. Given the single-group design, a between-group treatment comparison is not available in the recorded design.

What can the planning illustration establish?

The planning assumptions describe a hypothetical two-arm sample-size illustration using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is expressed as a fraction of the observed effect. For time-to-event outcomes, the stated approach concerns a total number of events; other outcomes are expressed as participants per arm. These are planning assumptions, not the trial’s own design justification. They do not describe the actual single-group dose-escalation structure.

As general statistical context, a sample-size calculation is conditional on its assumed effect, variability or event rate, analysis method, and design. A planning illustration does not show that a study had a particular probability of detecting an effect after the results were observed. It is not observed power. The registry record does not report the trial’s own sample-size justification, and the information does not include numeric planning outputs to interpret.

What analysis details are missing?

The registry record does not report the statistical analysis plan, interim analyses, analysis populations, missing-data methods, model specifications, or multiplicity procedures. It lists seven outcome measures and no analysis records. The absence of analysis details limits reproducibility and makes it difficult to determine how outcomes were summarized or how incomplete records were handled. It does not establish that no analyses were conducted; it means those details 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("TH-302 Plus Nab-paclitaxel Plus Gemcitabine")
n      <- c(18)
events <- c(1)
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  TH-302 Plus Nab-paclitaxel Plus Gemcitabine  18  1  5.6  0.1  27.3  1.0  25.8  1.3  26.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary DLT count and secondary measures of progression-free survival, objective response, duration of overall response, disease control, PET-based metabolic response, and treatment-emergent adverse events. The registry record does not report a multiplicity plan, a hierarchy for testing outcomes, or a statistical analysis plan. It is therefore not possible to determine whether any formal adjustment for multiple outcome assessments was intended or used.

As general statistical context, when several outcomes are tested, the chance of at least one apparently notable result can increase if each is interpreted separately. Prespecifying a primary outcome and a testing strategy can help clarify which analyses are confirmatory and which are descriptive. Here, the primary endpoint is identified, but formal testing procedures and outcome-specific analysis methods are not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The record notes that one participant was not evaluable for the primary endpoint because they did not complete Cycle 1. It does not say how that participant was treated in the analysis, whether other outcomes had missing data, or what missing-data methods were used. The analysis populations are not reported in the registry record. Enrollment of 19 should not be assumed to equal the denominator for every endpoint.

The registry record lists no analysis records. That does not prove that no statistical analyses were performed; it indicates that analysis details are not recorded in the available entry. The dose-escalation rules, interim analyses, stopping criteria, and approach to incomplete outcome data are not reported in the registry record. These omissions limit assessment of how planned analyses relate to the reported study objectives.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (15.8%), pneumonia (10.5%), pancytopenia (10.5%), cellulitis of male external genital organ (5.3%), urinary tract infection (5.3%).

The registry lists serious adverse event terms for the TH-302 plus nab-paclitaxel plus gemcitabine group. The leading listed terms are sepsis at 15.8%, pneumonia at 10.5%, and pancytopenia at 10.5%. Cellulitis of male external genital organ, urinary tract infection, and febrile neutropenia are each listed at 5.3%.

These percentages are registry entries, not a complete account of every safety outcome. The information available for this analysis does not specify event counts alongside the percentages, the seriousness criteria applied to each event, severity grades, timing, recurrence, relatedness to study treatment, or whether participants could contribute more than one term. The entries therefore should not be added together or interpreted as mutually exclusive participant groups.

The primary endpoint is DLT through Day 28 of Cycle 1, whereas the listed serious adverse event terms are a separate safety description. The registry record does not establish that any listed serious event met the DLT definition, and does not provide the DLT count. The record also does not report a numeric result for the secondary outcome of treatment-emergent adverse events in the information available for this analysis.

In general, safety percentages are most interpretable when their denominator, event definitions, follow-up period, and participant-level overlap are clear. Those details are not reported in the registry record for these terms. The entries should be read as reported safety listings, not as a causal comparison or a complete characterization of risk.

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

The record establishes that a Phase I, open-label, single-group dose-escalation trial was conducted to evaluate TH-302 with gemcitabine and nab-paclitaxel in previously untreated subjects with metastatic or locally advanced unresectable pancreatic adenocarcinoma. It identifies an early-cycle DLT count as the primary endpoint and states that the study aimed to assess safety, tolerability, and a recommended Phase 2 dose.

It does not establish how many participants experienced DLT, how precisely that count was estimated, which dose was selected, or what dose-specific outcomes were observed. The primary endpoint result is not reported in the registry record. One patient was noted as not evaluable because they did not complete Cycle 1, but the record does not describe how this was handled in an analysis.

The single-group design does not provide a randomized comparator for estimating differences between regimens. The record therefore cannot support a controlled comparative conclusion. Its open-label status and the lack of reported dose-level details further limit interpretation of outcome patterns. The registry also lists secondary outcome topics, but numerical results for them are not reported in the information available for this analysis.

As general statistical context, the absence of a reported estimate or confidence interval is different from evidence that an outcome did not occur. It means the uncertainty and magnitude of the primary endpoint cannot be judged from this record. The same applies to the listed serious adverse event terms: they are reported safety entries, but without complete event and denominator details they do not provide a full estimate of treatment-related risk.

The trial’s status is terminated. The reason for termination is not reported in the registry record. Termination alone does not explain the reason or imply a particular safety or efficacy outcome. The registry information supports describing the study’s aims, design, and listed safety terms, but not a conclusion about comparative benefit, lack of benefit, or the overall balance of outcomes.

14. Why This Trial Matters Statistically

This trial is statistically notable as an early-phase, single-group dose-escalation study with an explicitly defined early-cycle safety endpoint. Such a design addresses a different question from a randomized efficacy comparison: it is intended to characterize safety and support dose selection before later-phase evaluation. The registry identifies this purpose and the DLT assessment period, up to Day 28 of Cycle 1.

At the same time, the information needed to evaluate the primary statistical result is not reported in the registry record. There is no DLT count, analysis denominator, confidence interval, or dose-specific outcome. The note that one patient was not evaluable highlights why an analysis population and rules for incomplete assessment matter, particularly when the endpoint is based on a limited assessment window.

The single-group structure is also important for interpretation. Without a comparator, observed safety events are descriptive of the treated group and cannot be contrasted with outcomes under another assigned regimen. The registry’s serious adverse event listings add context, but they do not replace the primary DLT summary or resolve attribution and overlap questions.

The record lists several secondary outcomes, extending beyond safety to progression, response, and metabolic assessment. However, it does not report numerical results for these measures, the analysis methods, multiplicity procedures, or missing-data handling. This makes it difficult to assess the full analytic plan or relate the different outcome domains to one another.

Finally, the planning assumptions describe a hypothetical two-arm sample-size illustration, whereas the actual study is recorded as single-group. This distinction matters: a planning framework is not evidence about the trial’s observed precision or power. The trial’s own sample-size justification is not reported in the registry record. Together, these features illustrate why study design, endpoint reporting, and analysis transparency are necessary to interpret early-phase clinical data responsibly.

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 most direct limitation is that the registry record does not report the numeric result for the primary endpoint. Without the DLT count and its analysis denominator, the early-cycle safety outcome cannot be quantified. The record notes one participant was not evaluable because they did not complete Cycle 1, but it does not state how this participant was handled or whether other participants had incomplete assessments.

The study is single-group and open-label, with no separate comparator. Any outcomes would therefore be descriptive of the study group rather than a randomized estimate of differences between treatments. The record does not provide dose levels, dose-specific enrollment, escalation decisions, or the recommended Phase 2 dose, limiting interpretation of how the dose-finding objective was addressed.

The registry lists serious adverse event terms and percentages, but the information available for this analysis does not include corresponding event counts, severity grades, timing, relatedness, or details about overlap among participants. It also does not report numerical results for the listed secondary outcomes. These omissions prevent a full assessment of safety patterns and other clinical outcome domains.

Analysis methods are not described in the registry record. The statistical analysis plan, analysis populations, interim analyses, missing-data procedures, multiplicity approach, and sample-size justification are not reported. The registry lists no analysis records, which limits review of how planned outcomes were analyzed without establishing that no analyses took place.

The trial is listed as terminated, but the reason for termination is not reported in the registry record. The termination status alone does not indicate why the study ended or what the outcomes were. These limitations are specific to the information recorded for this trial and should be kept distinct from conclusions about the regimen itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer — NCT02047500.
• Registry record last updated 2025-05-11; status last verified 2025-05.
• Results first posted 2017-12-15.
• 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

NCT02047500 is recorded as a terminated, multicenter, open-label Phase I dose-escalation trial of TH-302 with gemcitabine and nab-paclitaxel in previously untreated subjects with metastatic or locally advanced unresectable pancreatic adenocarcinoma. The study is listed as single-group, with no masking and enrollment of 19. It started in 2014-01 and had a primary completion date of 2015-09.

The primary endpoint was the number of participants experiencing DLT up to Day 28 of Cycle 1. The registry notes one patient was not evaluable because they did not complete Cycle 1, but the numeric DLT result and handling of that participant are not reported in the registry record. Secondary outcomes include progression-free survival, response measures, PET-based metabolic response, and treatment-emergent adverse events.

The record lists serious adverse event terms and percentages, but does not report a complete numeric primary outcome or detailed analysis methods. Dose-escalation rules, the recommended Phase 2 dose, the reason for termination, and the trial’s statistical analysis plan are not reported in the registry record.