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 Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer (NCT00429858), a na phase 2 study. The primary outcome is Correlate Intratumoral Expression Level of Ribonucleotide Reductase Subunit 1 (RRM1) With Response to Gemcitabine in Patients With Advanced Pancreatic Cancer..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00429858 |
| Phase | Phase 2 |
| Condition | Pancreatic Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Andrew Ko |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced pancreatic cancer were the intended population. The registry describes the disease as locally advanced unresectable or metastatic pancreatic cancer, and lists pancreatic cancer as the condition. Enrollment was 21. The primary outcome description refers to patients with advanced pancreatic cancer, but the characteristics of the people who contributed tumor samples or outcome data are not reported in the registry record.
Intervention
The registered treatment sequence was gemcitabine monotherapy until disease progression, followed by gemcitabine plus S-1. The study also aimed to examine tumor gene expression in relation to response. The registry does not report how many participants received each part of the sequence, how long treatment continued, or whether all enrolled participants contributed biomarker measurements.
Comparator
There was no concurrent comparison group. The design is listed as a single-group study, and allocation is listed as not applicable. Therefore, the study was not designed as a randomized comparison of this treatment sequence against another treatment or control. Historical records were discarded under the university's record-retention policy, according to the registry entry.
Primary question
The primary question was whether intratumoral expression of RRM1 was associated with response to gemcitabine in patients with advanced pancreatic cancer. The planned summary was Pearson's correlation coefficient. This is an association question: it asks whether two measured characteristics vary together. It does not by itself establish that RRM1 predicts a difference in treatment benefit, or that changing treatment according to RRM1 would improve outcomes. The observed correlation and its uncertainty are not reported in the registry record.
3. Trial Design
This was a phase II, single-group clinical trial, registered as NCT00429858 under the title Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer. Its official title identifies it as Individualized Management of Pancreatic Cancer With Targeted Therapeutics (IMPACTT): A Phase II Clinical Trial. The listed sponsor was Andrew Ko. The study started on 2007-01-22, had a primary completion date of 2010-01-20, and is recorded as terminated. The registry lists enrollment of 21.
The intervention description specifies gemcitabine monotherapy until disease progression, followed by gemcitabine plus S-1. The study's stated rationale focused on examining tumor and blood samples to learn about molecular changes and biomarkers that might relate to treatment response. The primary outcome focused specifically on intratumoral RRM1 expression and response to gemcitabine. Secondary aims included other gene-expression relationships, overall survival, time to progression, dose modifications, and biomarker response classifications.
Masking is listed as none. The record does not describe a randomized allocation process or a concurrent control arm. The intervention sequence is therefore not a direct head-to-head comparison between gemcitabine and the combination. A response observed during treatment cannot be attributed to one regimen by comparing it with a separate randomized group in this study.
The record's status is terminated; it does not explain the reason for termination. A detailed protocol, recruitment flow, eligibility criteria, treatment exposure, and analysis population are not reported in the registry record. Enrollment alone does not establish how many people had usable biomarker and response measurements or were included in an analysis.
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 | Targeted Therapy Group |
|---|---|
| STARTED | 21 |
| COMPLETED | 19 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Targeted Therapy Group |
|---|---|
| Withdrawal by Subject | 1 |
| Study Termination | 1 |
Analysis population for the primary outcome, as defined in the registry: Historical records were discarded in accordance with university record retention policy.
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: Patient demographic data was retained electronically when transferred from legacy system.
| Characteristic | Unit | Targeted Therapy Group |
|---|---|---|
| Participants analysed | 21 | |
| Age, Customized: 40-49 years old | Participants | 2 |
| Age, Customized: 50-59 years old | Participants | 5 |
| Age, Customized: 60-69 years old | Participants | 11 |
| Age, Customized: 70-79 years old | Participants | 2 |
| Age, Customized: 80-89 years old | Participants | 1 |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 7 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | participants | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Correlate Intratumoral Expression Level of Ribonucleotide Reductase Subunit 1 (RRM1) With Response to Gemcitabine in Patients With Advanced Pancreatic Cancer., measured over Up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the relationship between intratumoral expression of ribonucleotide reductase subunit 1 (RRM1) and response to gemcitabine in patients with advanced pancreatic cancer. The registry specifies Pearson's correlation coefficient, denoted r, as the planned summary, with a timeframe of up to 2 years. The coefficient ranges from -1 to +1: the registry describes -1 as a perfect negative linear association, 0 as no association, and +1 as a positive linear association.
As a general statistical explanation, correlation is used to describe the direction and strength of a linear relationship between two measured variables. It can help characterize whether higher values of a biomarker tend to occur alongside higher or lower response measurements. It does not show that one variable causes the other, and it does not establish that the biomarker can select between treatments unless treatment comparisons and an appropriate predictive analysis support that conclusion.
The registry does not report how response was measured or encoded for the correlation, nor does it report an observed r, confidence interval, or p-value. The endpoint's intended measurement is therefore clear at a broad level, but the posted record does not permit assessment of the result or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry record states the primary question and proposed correlation method but does not report the resulting correlation. There is no posted estimate of the direction or strength of the relationship between tumor RRM1 expression and gemcitabine response. A conclusion about whether the measured variables were associated, or how precisely any association was estimated, cannot be drawn from the record.
Enrollment was 21, but this does not establish the number included in the primary analysis. The registry does not report the number with evaluable tumor expression measurements, the number with a response assessment, or the number with both. Without those details, the effective amount of information for the correlation is unknown. A study's enrollment count and its analysis population can differ, and the record does not describe any exclusions or missing measurements.
The design also constrains interpretation. This was a single-group study without a concurrent control. Its primary objective was an association between a biomarker and response to gemcitabine, not a randomized test of treatment efficacy. Even a reported correlation would not, on its own, show that RRM1 causes response differences or identifies who benefits more from gemcitabine than from another therapy. Those claims require evidence beyond a within-group association.
The treatment sequence included gemcitabine monotherapy until disease progression, then gemcitabine plus S-1. Secondary outcomes refer to relationships between other genes and response to the combination. The record does not provide treatment-specific outcome results or explain how the response endpoint was assigned when participants moved from one regimen to the next. This limits interpretation of any biomarker analysis across the sequence.
The registry lists several secondary outcomes, including median overall survival, median time to progression, dose modifications, and biomarker response measures. It does not report estimates for these outcomes. Their presence as planned or listed outcomes should not be mistaken for results. Similarly, the record's termination status is not an explanation of outcome quality or trial conduct; the reason for termination is not reported in the registry record.
General statistical interpretation: a point estimate describes the pattern in the analyzed data, while a confidence interval expresses uncertainty around that estimate under the chosen model. Neither is available for the primary association in this record. No significance test result is reported, and no evidence of a positive, negative, or null association should be inferred from the endpoint description alone.
9. Statistical Methods Explained
What does Pearson's correlation describe?
The registered primary analysis specifies Pearson's correlation coefficient, r, for the relationship between intratumoral RRM1 expression and response to gemcitabine. As a general statistical explanation, Pearson's r summarizes the direction and strength of a linear association between two quantitative measurements. A positive coefficient corresponds to a positive linear association, a negative coefficient to a negative linear association, and a coefficient of 0 to no linear association. The registry describes the endpoints of its scale as -1 and +1.
Correlation is not the same as a treatment effect. It does not quantify a difference between randomized treatment groups, and it does not establish that RRM1 is a causal mechanism. A biomarker can be associated with outcome for reasons that are not caused by the biomarker itself. Also, a correlation measures linear association; it may not capture other patterns between measurements. These are general properties of correlation, not findings from this trial.
What is missing from the reported analysis?
The registry does not report the observed correlation coefficient, the number of observations used in its calculation, a confidence interval, or a p-value. The description of a planned method is not a result. Without an estimate, readers cannot judge the direction or magnitude of the observed relationship. Without an interval or other uncertainty measure, they cannot assess how precise an estimate would be. Without analysis details, it is also not possible to assess how response was represented or whether the method's assumptions were examined.
As a general explanation, confidence intervals communicate the range of estimates compatible with the data under a specified statistical procedure and its assumptions. A narrow interval indicates more precision than a wide interval, but precision is distinct from clinical importance. The registry record reports no interval for this endpoint, so neither precision nor compatibility with different association sizes can be evaluated.
Why does the single-group design matter?
The study is listed as single-group, with no masking and no applicable allocation. The registered treatment sequence was gemcitabine until disease progression followed by gemcitabine plus S-1. This is not a randomized comparison of the two regimens. As a general statistical principle, a single-group biomarker association can describe variation among participants receiving the study treatment, but it cannot by itself separate treatment effects from other explanations for differences in response.
The registry does not report how response observations were handled across the treatment sequence. It is therefore not possible to determine from the record whether the primary correlation was based on response during gemcitabine monotherapy alone, how participants who proceeded to combination treatment were treated analytically, or how progression affected availability of later measurements. Those details should not be inferred.
How should the planning illustrations be understood?
Any sample-size figures associated with this analysis are planning illustrations based on an observed effect, not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a hypothetical two-arm planning calculation, not the observed single-group design of this study. They do not turn the study into a randomized comparison, and they do not establish that a particular level of power was achieved.
General statistical explanation: a sample-size calculation estimates the amount of information that might be needed under specified assumptions about an effect and an analysis. It is sensitive to the effect size used in planning and to departures from the assumptions. Observed power is not a substitute for reporting the estimate and its uncertainty after data collection. The registry does not report a trial-specific sample-size justification or a statistical analysis plan beyond the stated Pearson correlation description. Any additional rationale or prespecified analysis details are not reported in the registry record.
What can be concluded from the methods entry?
The record identifies the biomarker, outcome concept, summary measure, and timeframe for the primary question. It does not provide enough information to reproduce the analysis or evaluate its assumptions. The response definition, data handling, missing-data approach, outlier handling, covariate adjustment, and inferential procedure are not reported in the registry record. These gaps matter because correlation estimates depend on which participants and measurements are included and on how the variables are defined. No recalculated result can be derived from the posted summary because the necessary outcome statistics are absent.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary biomarker question and several secondary outcomes. These include relationships between other intratumoral gene-expression levels and response, median overall survival, median time to progression, dose modifications, and biomarker response classifications. It does not report results for these outcomes or explain whether analyses were prespecified, adjusted for multiple testing, or treated as exploratory. A multiplicity strategy is not reported in the registry record.
As a general statistical explanation, when many hypotheses are examined, the chance of observing at least one apparently notable result can increase. Methods for addressing multiplicity can control error rates or help distinguish confirmatory from exploratory analyses. The registry entry does not state which, if any, approach was used. It is therefore not possible to interpret a pattern of statistical significance across outcomes, and no such pattern is reported in any case.
The record says historical records were discarded in accordance with university record-retention policy. It does not provide participant-level data, an analysis population, or counts for missing biomarker and response measurements. The handling of missing data, the reasons for missingness, and any imputation or sensitivity analyses are not reported in the registry record. Enrollment of 21 should not be treated as the number analyzed for every endpoint.
Definitions of the analysis populations, such as whether all enrolled participants or only those with evaluable measurements were included, are not reported in the registry record. The status of participants who did not complete treatment or did not proceed to combination therapy is also not described. These omissions prevent assessment of attrition and of how the population analyzed may relate to the original enrollment.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Targeted Therapy Group | 9 | 21 | 42.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Targeted Therapy Group | 7 of 21 |
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 |
|---|---|
| Targeted Therapy Group | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Targeted Therapy Group |
|---|---|---|
| Thrombosis/thrombus/embolism | Blood and lymphatic system disorders | 2 of 21 |
| Abdominal Pain | Gastrointestinal disorders | 2 of 21 |
| Nausea | Gastrointestinal disorders | 2 of 21 |
| Pain, NOS | General disorders | 2 of 21 |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | 1 of 21 |
| Colitis | Gastrointestinal disorders | 1 of 21 |
| Vomitting | Gastrointestinal disorders | 1 of 21 |
| Hyperbilirubinemia | Hepatobiliary disorders | 1 of 21 |
| Encephalopathy | Nervous system disorders | 1 of 21 |
| Hemorrhage, GI - Duodenum | Gastrointestinal disorders | 1 of 21 |
Serious events with the highest arm-level rate: thrombosis/thrombus/embolism (9.5%), abdominal pain (9.5%), nausea (9.5%), pain, nos (9.5%), upper gastrointestinal hemorrhage (4.8%).
The registry's serious adverse event entry lists a Targeted Therapy Group with 21 at risk and 9 affected. It lists 0 at risk and 0 affected for other events, and records 7 deaths. These are the registry's safety figures; they should not be interpreted as proof that treatment caused the events or deaths. The relationship of each event to treatment, its timing, severity details, and the circumstances of the deaths are not reported in the registry record.
The most frequently listed serious-event terms include thrombosis/thrombus/embolism, abdominal pain, nausea, and pain, NOS, each reported as 9.5%. Upper gastrointestinal hemorrhage and colitis are each reported as 4.8%. These percentages are presented as recorded. The registry does not explain the event coding details or provide a narrative linking each event to a particular drug or treatment phase.
Serious adverse event summaries are not the same as a complete account of all symptoms or treatment tolerability. The record does not provide the full adverse-event profile, event duration, management, exposure-adjusted rates, or a randomized comparator. The figures therefore describe reported serious-event entries in this study, not comparative safety or a causal estimate.
12. What the Result Does, and Does Not, Mean
The registry establishes that a phase II study was conducted to examine gene expression in relation to treatment response in pancreatic cancer. Its primary question concerned whether tumor RRM1 expression was associated with response to gemcitabine, and the specified summary was Pearson's correlation. The record also describes a treatment sequence of gemcitabine monotherapy until disease progression followed by gemcitabine plus S-1.
What the record does not establish is the observed direction, size, or precision of the primary association. The correlation coefficient, confidence interval, p-value, response definition, and number of analyzed observations are not reported in the registry record. The clinical and statistical meaning of the primary result therefore cannot be judged from the posted results, because that result is absent.
The study's single-group design means it does not provide a randomized comparison of the treatment sequence with another treatment. The primary biomarker question is an association question, not a direct test of whether selecting treatment based on RRM1 improves outcomes. Even if an association estimate were available, correlation alone would not demonstrate causation or establish a biomarker-guided treatment strategy.
The listed secondary outcomes and serious adverse event summaries add context about what the trial intended to assess and what safety information was entered. They do not substitute for a reported efficacy analysis, and the event summaries do not establish that treatment caused the events. The reason for termination, detailed treatment exposure, and outcome analyses are not reported in the registry record.
The appropriate reading is consequently limited: this record documents the trial's design and questions, but does not provide the outcome evidence needed to evaluate the primary biomarker association or the listed secondary endpoints. No conclusion about treatment effectiveness or lack of effectiveness follows from the absence of results in the registry.
13. Why This Trial Matters Statistically
This study illustrates the distinction between a biomarker association and a treatment-comparison question. RRM1 expression was to be related to response to gemcitabine using Pearson's correlation. That analysis, if reported, would describe whether the measurements varied together within the analyzed data. It would not by itself show that RRM1 predicts a different benefit from gemcitabine than from another regimen. Keeping those questions separate is important when interpreting biomarker research.
The treatment sequence also matters statistically. Participants were described as receiving gemcitabine until disease progression and then gemcitabine plus S-1. A biomarker relationship tied to response during one part of a sequence is not automatically interchangeable with a relationship tied to response during another part. The registry does not provide the details needed to understand how that distinction was handled in the primary or secondary analyses.
The record is also a reminder that a planned endpoint and an analysis result are different kinds of evidence. The primary outcome description is specific about the biomarker, response concept, correlation method, and timeframe, but the coefficient and its uncertainty are absent. Without those results, readers cannot assess the association's direction, magnitude, precision, or robustness.
Finally, the single-group design and incomplete analysis reporting place limits on causal interpretation and reproducibility. Missing information about the analysis population, response definition, and missing-data handling leaves important questions unanswered. These are not merely technical details: they determine what the estimated association would represent and how much confidence could be placed in it.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not report the primary correlation result or the results for the listed secondary outcomes. It also does not provide confidence intervals, p-values, or the number of observations used for each analysis. As a result, neither the magnitude nor precision of the proposed biomarker relationships can be assessed.
The record's primary outcome description does not define the response measure or explain how it was coded for Pearson's correlation. It does not state whether the analysis adjusted for other variables, how outliers were handled, or how the assumptions of the correlation analysis were assessed. These methods are not reported in the registry record.
Although enrollment was 21, the record does not identify the number with usable tumor-expression and response data. It does not describe missing measurements, exclusions, treatment completion, or the populations analyzed for primary and secondary outcomes. Historical records were discarded under the university's record-retention policy, as stated in the primary outcome entry, limiting the information available in the registry record.
The single-group design has no concurrent randomized comparator. It cannot support a direct between-treatment estimate, and the sequential treatment means that the relationship of response to each treatment phase needs clear definition. The registry does not report how the treatment transition or progression was incorporated into outcome analyses.
The study is marked terminated, but the reason is not reported in the registry record. Masking is listed as none. The record does not provide a detailed protocol, a trial-specific sample-size justification, or a statistical analysis plan beyond the Pearson correlation description. These limitations restrict assessment of conduct, prespecification, reproducibility, and the scope of any conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer — NCT00429858.
- Registry record last updated 2020-09-18; status last verified 2020-08.
- Results first posted 2020-09-18.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00429858 is a phase II, single-group study of gemcitabine followed by gemcitabine plus S-1 for locally advanced unresectable or metastatic pancreatic cancer. The registry lists enrollment of 21, no masking, and terminated status. The study started on 2007-01-22, with primary completion on 2010-01-20.
The primary question concerned the association between intratumoral RRM1 expression and response to gemcitabine, using Pearson's correlation over a timeframe of up to 2 years. Secondary outcomes included additional gene-expression questions, survival and progression measures, dose modifications, and biomarker response classifications.
The registry record does not report the primary correlation estimate, its uncertainty, or results for the secondary outcomes. It also does not report the analysis population, response definition, missing-data approach, or reason for termination. The serious-event entry lists 9 affected in the Targeted Therapy Group and records 7 deaths; event attribution is not reported.