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 EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX (NCT03126435), a randomized phase 3 study. The primary outcome is Overall Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03126435 |
| Phase | Phase 3 |
| Condition | Metastatic Pancreas Cancer, Locally Advanced Pancreatic Cancer, Pancreatic Adenocarcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 218 |
| Arms in the primary outcome | 2 |
| Lead sponsor | SynCore Biotechnology Co., Ltd. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with measurable locally advanced or metastatic pancreatic adenocarcinoma whose disease had failed on FOLFIRINOX. The registry record describes pancreatic cancer as the condition and reports a total enrollment of 218.
Intervention
EndoTAG-1 combined with gemcitabine. The recorded regimen specifies EndoTAG-1 22 mg/m² twice weekly and gemcitabine 1000mg/m² once weekly, with treatment and rest periods within an 8-week cycle.
Comparator
Gemcitabine monotherapy, recorded as gemcitabine 1000mg/m² once weekly with treatment and rest periods within an 8-week cycle.
Primary question
Does adding EndoTAG-1 to gemcitabine improve overall survival compared with gemcitabine alone in this population? Overall survival was measured from randomization to death from any cause or the last day known to be alive.
3. Trial Design
This was a randomized, open-label, parallel-group phase 3 trial sponsored by SynCore Biotechnology Co., Ltd. The registry record lists 218 participants as enrolled and marks the study completed. It identifies the population as people with measurable locally advanced or metastatic pancreatic adenocarcinoma after failure on FOLFIRINOX.
Participants were assigned to EndoTAG-1 plus gemcitabine or gemcitabine monotherapy. The primary outcome was overall survival, defined from randomization until death from any cause or the last day a participant was known to be alive. The record gives a follow-up timeframe of up to approximately 33.5 months, with assessment continuing during treatment. It also describes the trial as adaptive, but details of any adaptation, its timing, or its effect on the analysis are not reported in the registry record.
The primary outcome results include 108 participants in the EndoTAG-1 and gemcitabine arm and 110 in the gemcitabine-alone arm. Median overall survival was 226 days (95% confidence interval 183 to 278) and 209 days (95% confidence interval 158 to 248), respectively. The registry reports a log-rank comparison. It does not report a hazard ratio in the posted results.
The study was not masked. Participants and clinical staff could therefore know the assigned treatment. The registry record does not report how randomization was generated or concealed, nor does it give a fuller statistical analysis plan. Those details should not be inferred from the trial's phase, allocation, or adaptive 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.
Overall Study
| Stage | EndoTAG-1 and Gemcitabine | Gemcitabine Monotherapy |
|---|---|---|
| STARTED | 108 | 110 |
| COMPLETED | 2 | 6 |
| NOT COMPLETED | 106 | 104 |
Reasons for not completing this period:
| Reason | EndoTAG-1 and Gemcitabine | Gemcitabine Monotherapy |
|---|---|---|
| Death | 90 | 84 |
| Lost to Follow-up | 4 | 3 |
| Physician Decision | 0 | 1 |
| Withdrawal by Subject | 6 | 12 |
| e.g. Sponsor Decision, General Deterioration... | 6 | 4 |
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 | EndoTAG-1 and Gemcitabine | Gemcitabine Monotherapy | Total |
|---|---|---|---|---|
| Participants analysed | 108 | 110 | 218 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 69 | 72 | 141 |
| Age, Categorical: >=65 years | Participants | 39 | 38 | 77 |
| Age, Continuous | years | 60.7 (SD 9.98) | 61.7 (SD 9.68) | 61.2 (SD 9.82) |
| Sex: Female, Male: Female | Participants | 38 | 50 | 88 |
| Sex: Female, Male: Male | Participants | 70 | 60 | 130 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 35 | 31 | 66 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): White | Participants | 56 | 59 | 115 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 15 | 18 | 33 |
| Region of Enrollment: South Korea | participants | 13 | 18 | 31 |
| Region of Enrollment: Hungary | participants | 15 | 17 | 32 |
| Region of Enrollment: United States | participants | 6 | 8 | 14 |
| Region of Enrollment: Taiwan | participants | 21 | 13 | 34 |
| Region of Enrollment: Israel | participants | 7 | 6 | 13 |
| Region of Enrollment: France | participants | 20 | 21 | 41 |
| Region of Enrollment: Russia | participants | 26 | 27 | 53 |
| Extent of Disease at Randomization: Metastatic | Participants | 94 | 95 | 189 |
| Extent of Disease at Randomization: Locally Advanced | Participants | 14 | 15 | 29 |
| ECOG Performance at Randomization: 0 | Participants | 49 | 48 | 97 |
| ECOG Performance at Randomization: 1 | Participants | 59 | 62 | 121 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival, measured over From randomization to death from any cause or last day known to be alive, up to approximately 33.5 months (assessed continuously during treatment).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
Overall survival measures the time from randomization until death from any cause. For a participant still known to be alive at the analysis, the recorded time is censored at the last day known to be alive. The registry describes the endpoint in those terms and reports medians with 95% confidence intervals.
Time to death is used in clinical trials because it incorporates both whether an event occurred and how long participants were followed before the event or censoring. A median is the point in the estimated survival-time distribution at which half of the participants are expected to have had the event and half are expected to remain alive. It is not an average survival time, and it does not describe every participant's outcome.
Comparing medians alone does not fully characterize the difference between survival distributions. The registry's log-rank test compares the observed pattern of deaths over follow-up between the arms. Its result is therefore relevant alongside, rather than interchangeable with, the arm-specific median estimates and their confidence intervals. A hazard ratio and its confidence interval would offer another way to describe a time-to-event contrast, but a hazard ratio is not reported in the registry record.
The endpoint includes death from any cause, not only deaths attributed to pancreatic cancer or trial treatment. Censoring is necessary when a participant's death is not observed by the analysis, but the registry does not detail censoring rules beyond the last day known to be alive.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The median overall survival was 226 days in the EndoTAG-1 plus gemcitabine arm and 209 days in the gemcitabine-alone arm. The corresponding 95% confidence intervals were 183 to 278 days and 158 to 248 days. These are arm-specific estimates; the registry does not report a hazard ratio or a confidence interval for a relative time-to-event effect.
The reported log-rank p-value is greater than 0.05. Thus, the posted primary analysis does not establish a statistically significant difference between the survival distributions at the 0.05 level. This should not be turned into a claim that the arms are identical: a non-significant result can reflect uncertainty, and the medians and their intervals do not determine the full shape of survival over time.
The confidence intervals around the two medians overlap. A confidence interval gives a range of values compatible with the data under the method's assumptions; it is not a range containing a fixed proportion of individual survival times. Overlap of the separate arm intervals is not itself the formal test of the treatment contrast. The registry's reported inferential comparison is the log-rank test.
The overall survival analysis included 108 participants in the combination arm and 110 in the monotherapy arm. The record describes events as deaths and refers to participants censored at analysis. It does not provide the number of deaths used in the primary comparison or the number censored in each arm. Consequently, the medians and p-value do not by themselves show how many participants contributed observed deaths or how follow-up was distributed.
The secondary outcomes add context but do not overturn the primary result. For the three secondary outcomes with posted arm counts and comparisons, the sponsor's reported logistic-regression p-values are above 0.05. The registry lists five secondary outcomes, while results for progression-free survival and duration of response are not reported in the registry record. Interpretation of the secondary findings also needs to account for the absence of reported multiplicity procedures and the different analyzed participant counts for some outcomes.
Overall, the posted evidence describes similar estimated median survival times, with uncertainty around both estimates, and a log-rank test that does not meet the 0.05 threshold. It does not provide enough comparative time-to-event detail to quantify the size or precision of a relative survival effect beyond that test.
9. Statistical Methods Explained
What does the median describe?
For a time-to-event outcome, the median is a summary of the estimated time until the event. Here, the event is death from any cause. Participants who are alive at their last recorded observation contribute information up to that time and are censored rather than counted as having died. The median is therefore a summary of a survival distribution, not the arithmetic average of observed follow-up times.
The registry reports median overall survival of 226 days for EndoTAG-1 plus gemcitabine and 209 days for gemcitabine alone. It gives 95% confidence intervals for each median. A confidence interval represents uncertainty in an estimated quantity under the statistical method's assumptions. It does not mean that the true value has a 95% probability of lying in the particular interval after the data have been observed. Nor do these arm-specific intervals directly give a confidence interval for the difference between arms.
Why use a log-rank test?
The log-rank test is a standard way to compare time-to-event distributions. In general, it uses information about the timing of events across follow-up, including the time at which participants are censored. It tests whether the observed survival experience differs between groups under its assumptions; it does not report the size of that difference. The registry identifies the primary comparison as a log-rank test and reports a p-value greater than 0.05.
A p-value measures how unusual data at least as incompatible with the null hypothesis would be if that hypothesis and the test assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. A result above the stated 0.05 significance level does not demonstrate equivalence or prove that no effect exists. The registry does not report a hazard ratio or confidence interval for the comparative survival effect, so the magnitude and precision of that relative effect cannot be read from the posted primary analysis.
How should the secondary binary outcomes be read?
Objective response, disease control, and CA 19-9 response are recorded as participant counts. For these binary outcomes, the posted results give counts and analyzed denominators in each arm. The recalculated unadjusted comparisons express the difference in observed proportions, with confidence intervals. In general, a risk-difference confidence interval that includes zero is compatible with both a lower and a higher proportion in one arm, as well as no difference under the interval method's assumptions. The intervals for these comparisons span zero.
The registry also reports logistic-regression analyses for the secondary response outcomes. Those are the sponsor's analyses and are not identical to a simple unadjusted comparison of the posted counts. Adjustment details are not reported in the registry record. The sponsor's analysis takes precedence when describing the trial's reported inferential result; the recalculated comparisons are descriptive checks based on summary counts, not replacements for the trial's planned analysis.
What do the planning illustrations mean?
The sample-size illustrations use the observed effect as a starting point and consider planning for 100%, 75%, or 50% of that observed effect. They use a two-sided significance level of 0.05, equal allocation, and a normal approximation. For binary outcomes, the displayed values are participants per arm for 80% or 90% power. They are planning illustrations, not observed power and not the trial's original sample-size justification.
Observed effects can be unstable, particularly when event counts are small. Planning around a fraction of an observed effect makes the assumptions visible, but it does not establish that a future trial should use those assumptions. The registry record does not report the original sample-size justification, target effect, or power calculation. These illustrations should not be mistaken for evidence that the completed study was adequately or inadequately powered.
Why does over-dispersion matter in general?
Over-dispersion occurs when the variability in count data exceeds what a statistical model assumes. In general, ignoring it can make standard errors too small and confidence intervals too narrow. The primary outcome is time to event, and the posted secondary results include binary counts; the registry record does not describe an over-dispersion assessment or a count model. This general issue should not be taken as a claim that over-dispersion affected this trial.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Log Rank | not reported | 0.665 |
The sponsor's reported primary analysis is a log-rank test, with a p-value greater than 0.05. The posted arm-specific medians and confidence intervals provide useful descriptive information, but they are not a recalculated treatment comparison. A simple comparative reconstruction is not appropriate from medians alone because it would discard event timing and censoring information. The registry record does not report a hazard ratio for the primary outcome, so there is no sponsor-reported relative effect estimate to compare with a recalculation.
For the secondary binary outcomes with posted counts, unadjusted recalculations compare proportions using the summary counts. The sponsor reports logistic-regression tests for those outcomes. The sponsor's analysis takes precedence when describing the trial's own inferential findings; the unadjusted calculations are not substitutes for that analysis. The sponsor's reported p-values for these posted secondary analyses are also above 0.05.
The registry record does not provide enough detail to reproduce the sponsor's models, including any covariates or other adjustments. Differences between an unadjusted calculation and a regression result can arise because the methods and information used differ; the record does not establish which specific feature accounts for any difference. The posted analyses should therefore be described as reported rather than treated as fully independently verified.
11. Multiplicity, Missing Data and Analysis Populations
The registry record lists several secondary outcomes in addition to overall survival. It reports results for three secondary outcomes, but results for progression-free survival and duration of response are not reported in the registry record. The number of posted analyses does not establish which outcomes were included in a prespecified testing sequence or how confirmatory claims were intended to be made.
Multiplicity arises when more than one hypothesis is tested. In general, testing many outcomes without an appropriate strategy can increase the chance of a false-positive finding across the set. The registry record does not report whether the trial used a multiplicity adjustment, a gatekeeping sequence, or another approach. Consequently, isolated secondary p-values should not be interpreted as if they necessarily had the same confirmatory status as the primary test.
Missing-data methods are also not reported in the registry record. For overall survival, the endpoint description says that follow-up runs from randomization to death or the last day known to be alive, and it refers to participants censored at analysis. It does not give arm-specific censoring counts, reasons for loss of follow-up, or further censoring rules. For secondary outcomes, analyzed denominators vary, and the registry does not explain the difference between those denominators and the randomized arm sizes.
The record does not specify the analysis populations used for the primary and secondary analyses, such as whether participants were analyzed according to randomized assignment or another population definition. It also does not report how missing response assessments were handled. These omissions limit assessment of potential bias and reproducibility; they are not evidence that a particular handling method was used.
The trial is described as adaptive, but the adaptation procedures, any interim analyses, and any adjustment to preserve the intended error rate are not reported in the registry record. No inference about interim monitoring or changes to the design should be made without those details.
12. 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 |
|---|---|---|---|
| EndoTAG-1 and Gemcitabine | 52 | 102 | 51.0% |
| Gemcitabine Monotherapy | 48 | 102 | 47.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| EndoTAG-1 and Gemcitabine | 91 of 108 |
| Gemcitabine Monotherapy | 85 of 110 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| EndoTAG-1 and Gemcitabine | 101 of 102 |
| Gemcitabine Monotherapy | 100 of 102 |
Most frequent serious adverse event terms
| Event term | Organ system | EndoTAG-1 and Gemcitabine | Gemcitabine Monotherapy |
|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 6 of 102 | 5 of 102 |
| Pyrexia | General disorders | 7 of 102 | 1 of 102 |
| Anaemia | Blood and lymphatic system disorders | 4 of 102 | 1 of 102 |
| Pneumonia | Infections and infestations | 2 of 102 | 3 of 102 |
| Asthenia | General disorders | 3 of 102 | 1 of 102 |
| Death | General disorders | 0 of 102 | 4 of 102 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 102 | 2 of 102 |
| Abdominal pain upper | Gastrointestinal disorders | 2 of 102 | 1 of 102 |
| Ascites | Gastrointestinal disorders | 2 of 102 | 1 of 102 |
| Duodenal obstruction | Gastrointestinal disorders | 0 of 102 | 3 of 102 |
Most frequent non-serious adverse event terms
| Event term | Organ system | EndoTAG-1 and Gemcitabine | Gemcitabine Monotherapy |
|---|---|---|---|
| Platelet Count Decreased | Investigations | 41 of 102 | 42 of 102 |
| Decreased Appetite | Metabolism and nutrition disorders | 35 of 102 | 22 of 102 |
| Constipation | Gastrointestinal disorders | 20 of 102 | 20 of 102 |
| Neutrophil Count Decreased | Investigations | 18 of 102 | 21 of 102 |
| White Blood Cell Count Decreased | Investigations | 18 of 102 | 17 of 102 |
| Fatigue | General disorders | 19 of 102 | 16 of 102 |
| Alanine Aminotransferase Increased | Investigations | 17 of 102 | 17 of 102 |
| Aspartate Aminotransferase Increased | Investigations | 14 of 102 | 17 of 102 |
| Chills | General disorders | 18 of 102 | 6 of 102 |
| Oedema Peripheral | General disorders | 18 of 102 | 6 of 102 |
Serious events with the highest arm-level rate: pyrexia (6.9%), abdominal pain (5.9%), anaemia (3.9%), death (3.9%), duodenal obstruction (2.9%).
The registry reports serious adverse events in 52 of 102 participants at risk in the EndoTAG-1 and gemcitabine arm and 48 of 102 in the gemcitabine-alone arm. It also reports other adverse events affecting 101 of 102 and 100 of 102, respectively. These are counts from the safety record and should be read with their stated denominators, not as randomized-arm totals.
The registry lists deaths in 91 participants in the combination arm and 85 in the monotherapy arm. Those figures should not be interpreted as deaths caused by treatment: the record does not establish attribution, and overall-survival deaths include death from any cause. It does not give a comparative safety analysis or a detailed account of timing and relatedness for these deaths.
Among the listed serious adverse-event terms, pyrexia is reported at 6.9%, abdominal pain at 5.9%, anaemia and death at 3.9% each, and duodenal obstruction and asthenia at 2.9% each. These terms and percentages do not replace a full safety assessment. The registry record does not provide enough context to infer comparative risk or causation from the listed events alone.
13. What the Result Does, and Does Not, Mean
The posted results show median overall survival of 226 days in the EndoTAG-1 plus gemcitabine arm and 209 days in the gemcitabine-alone arm. The sponsor's log-rank comparison has a p-value above 0.05. In statistical terms, the posted primary analysis does not establish a difference in overall survival at the 0.05 level.
That conclusion is narrower than saying the treatments have identical effects. Failure to meet a significance threshold does not prove equivalence, and the registry does not report an equivalence or non-inferiority analysis. Nor does the result establish that any possible difference is clinically important or unimportant. The median estimates are uncertain, and the reported p-value does not provide a direct estimate of the size of a relative survival effect.
The findings also do not establish the result for every secondary outcome. The available sponsor analyses for the posted secondary comparisons are above 0.05, while results for two listed secondary endpoints are not reported in the registry record. Missing analysis details, different denominators, and the lack of reported multiplicity procedures constrain how broadly these findings can be generalized.
Safety counts should be interpreted separately from efficacy. Serious adverse events and deaths are reported, but the figures alone do not determine whether an event was caused by a treatment or whether the arms differ in risk. The registry record does not report enough attribution and comparative analysis detail to support those conclusions.
In short, the registry reports a randomized comparison with arm-specific survival estimates and a non-significant log-rank result. It does not demonstrate superiority on the primary endpoint, but it also does not establish that the two regimens are equivalent or that no effect is possible.
14. Why This Trial Matters Statistically
This trial is statistically important to interpret because the primary endpoint is time to event, while several secondary outcomes are binary. These outcome types require different summaries and analyses. A pair of medians is not enough to reconstruct a relative survival estimate, especially when participants may be censored at different times. The registry reports a log-rank test but not a hazard ratio, so readers should distinguish the reported test result from an effect-size estimate that is not posted.
The open-label design is another relevant feature. In general, knowledge of treatment assignment can influence care or assessment, particularly for outcomes requiring judgment. Death is less dependent on subjective assessment than some response outcomes, but the record does not detail outcome-assessment procedures or safeguards. This is a design consideration, not evidence that bias occurred.
The secondary outcomes illustrate why endpoint hierarchy and multiplicity matter. Several outcomes are listed, but the record does not report how their testing was organized or whether adjustment was used. The missing results for progression-free survival and duration of response also mean that the secondary evidence cannot be assessed in full.
Finally, the trial's adaptive label does not reveal how adaptation was implemented. Without details about decision rules or interim analyses, readers cannot evaluate whether those features affected the analysis. The record supports a careful description of the posted results, while leaving important aspects of the statistical plan and execution unresolved.
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 record provides medians and confidence intervals for overall survival, and a log-rank p-value, but no hazard ratio or confidence interval for the comparative effect. The number of deaths and censoring by arm is not reported. This limits assessment of the primary result's precision and makes an independent time-to-event reconstruction from the posted summaries inappropriate.
The study is called adaptive, but adaptation procedures and interim analyses are not described in the registry record. The record also does not report the original sample-size justification or the analysis populations. The planning illustrations based on observed effects are not a substitute for the trial's design assumptions.
For the secondary outcomes, results are not reported in the registry record for progression-free survival and duration of response. The analyzed denominators differ for some posted outcomes, and reasons for those differences and handling of missing assessments are not specified. The registry also does not describe covariates in the logistic-regression analyses or a multiplicity strategy.
The open-label design and limited reporting of allocation procedures and outcome-assessment safeguards leave additional questions about trial conduct. These are reporting limitations; they do not by themselves show that bias occurred. Safety reporting includes affected counts and selected serious-event terms, but does not provide sufficient attribution or comparative analysis detail to infer treatment causation.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX — NCT03126435.
- Registry record last updated 2023-05-06; status last verified 2023-05.
- Results first posted 2023-03-24.
- 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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19. Record Summary
NCT03126435 was a randomized, open-label, parallel-group phase 3 trial of EndoTAG-1 plus gemcitabine versus gemcitabine alone in locally advanced or metastatic pancreatic adenocarcinoma after FOLFIRINOX failure. The registry lists 218 participants enrolled and the study status as completed.
Overall survival was the primary endpoint. Median survival was 226 days in the combination arm and 209 days in the monotherapy arm; the reported log-rank p-value was above 0.05. The record also lists five secondary outcomes, with results posted for three. Details of the adaptive procedures, multiplicity handling, missing-data methods, analysis populations, and the original sample-size justification are not reported in the registry record.