Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer (NCT01666730), a na phase 2 study. The primary outcome is Median Overall Survival (OS).

2. Clinical Question

The study was registered as a phase II trial of metformin plus modified FOLFOX 6 in metastatic pancreatic cancer. Its primary endpoint focuses on time from treatment initiation to death from any cause, with assessment described as extending up to 1 year. The record also identifies response rate, clinical benefit rate, progression-free survival, and grade 3 and 4 toxicities as secondary outcomes.

Because the study has a single group and no like-for-like control, it does not directly estimate a treatment difference against another regimen or a control condition. The central question is descriptive: what survival and other recorded outcomes occurred among people receiving the combination? The registry record does not report the primary endpoint result, the secondary outcome results, or analyses that would answer that question. Completion status alone does not establish what those results were.

3. Trial Design

This is a phase II, single-group study sponsored by Case Comprehensive Cancer Center. The registry lists an enrollment of 50 and records the study as completed. Its start date is 2013-02-21, and its primary completion date is 2018-08-01. Allocation is recorded as not applicable, and masking as none. There is no concurrent comparison group described, so the study is not a randomized comparison.

The treatment group is described as receiving metformin hydrochloride by mouth twice daily on days 1-14, together with FOLFOX on day 1. FOLFOX is described as leucovorin calcium given intravenously over 120 minutes, fluorouracil given by continuous intravenous infusion over 46 hours, and oxaliplatin given intravenously over 120 minutes. Courses are described as repeating every 14 days. The registry’s treatment description also refers to stopping treatment in the absence of disease progression or unacceptable toxicity, but the record text does not give a complete description of that clause.

Laboratory biomarker analysis is listed as an intervention. The outcome list includes overall survival as the primary endpoint and response rate, clinical benefit rate, progression-free survival, and grade 3 and 4 toxicities as secondary outcomes. The registry record does not report a detailed protocol, eligibility criteria beyond the listed conditions, the analysis population, or a statistical analysis plan. It also does not report a control regimen or an allocation procedure. The design therefore supports a description of outcomes in the treated group, but not a direct estimate of how those outcomes compare with outcomes under another treatment.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

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: Participants enrolled in study

6. Primary Endpoint

The registry lists the primary outcome as Median Overall Survival (OS), measured over Time from first day of treatment to death from any cause, assessed up to 1 year.

The primary endpoint is median overall survival. The registry defines the time interval as running from the first day of treatment to death from any cause, with assessment described as up to 1 year. Overall survival is a time-to-event outcome: the event is death, and the endpoint captures how long participants remain alive after the specified starting point.

A median is the time by which half of the relevant population is estimated to have experienced the event and half is estimated not to have experienced it. It offers a summary of the observed survival-time distribution without requiring every participant’s survival time to be the same. In a study with incomplete follow-up, methods for time-to-event data can account for participants whose event time is not observed during their available follow-up; the registry record does not describe the censoring details for this study.

The record says the survival curve is calculated using Kaplan-Meier methods and that the median is estimated assuming an exponential distribution. The exponential assumption is a modeling choice used for estimating the median; its implications are discussed in the statistical methods explanation. The endpoint is paired with a 95% confidence interval, which would convey uncertainty around the estimate. Neither the median overall survival nor its confidence interval is reported in the registry record, so the size and precision of the endpoint estimate cannot be assessed from the posted results described in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Overall survival is a time-to-event endpoint. Each participant contributes a duration measured from the specified origin, here the first day of treatment, until death from any cause or until the end of observed follow-up if death has not been observed. In general, this type of analysis uses information from participants with differing amounts of follow-up rather than treating every participant as if they had the same observation period. The registry record does not report how follow-up ended for individual participants or describe censoring rules.

What does the Kaplan-Meier method estimate?

In general, the Kaplan-Meier method estimates the probability of remaining event-free over time while accounting for the timing of observed events and censoring. The resulting survival curve changes when events occur and reflects the available follow-up at each point. It relies on assumptions about censoring: broadly, that the reason follow-up ends does not make a participant’s future event risk systematically different in a way that invalidates the estimate. Study-specific checks of this assumption are not reported in the registry record.

The median survival is read from the estimated survival distribution as the time at which the estimated probability of surviving reaches the midpoint. If the curve does not reach that point within observed follow-up, the median may not be estimable from the available data. Whether that occurred in this trial is not reported in the registry record, and no median result is posted. A median gives a single summary point; it does not describe the full shape of the survival curve or show how survival differs over all follow-up times.

Why does the exponential assumption matter?

The record states that the median will be estimated assuming an exponential distribution. In general, an exponential model assumes a constant event hazard over time: the instantaneous event rate does not change with elapsed time among those still at risk. This can make estimation convenient, but it is a substantive modeling assumption, not simply a neutral way to display a Kaplan-Meier curve. If the event pattern changes over time, an exponential model may not represent that pattern well. The registry record does not report diagnostics, a comparison with other models, or a rationale for this assumption. It is therefore not possible to assess from the record whether the assumption is compatible with the observed survival data.

How should the confidence interval be read?

A confidence interval expresses statistical uncertainty around an estimate under the method’s assumptions. A 95% confidence interval is intended to convey the range of values reasonably compatible with the data and analysis procedure. It is not a guarantee that the true value lies in that particular interval, and it does not account for every possible source of bias, such as selection or measurement problems. The registry specifies a 95% confidence interval for the median but does not report its limits. The precision of the survival estimate therefore cannot be judged from the registry record.

What can a single-group analysis establish?

A single-group time-to-event analysis can describe outcomes for the treated group under the study’s follow-up and measurement procedures. It does not provide a randomized estimate of the difference between treatment strategies. In general, a comparison requires a suitable comparator and a clear contrast in the analysis; neither is described for this trial. Any unadjusted comparison with a separate population would require caution because populations and study procedures may differ. The registry record does not report a sponsor hazard ratio, and no comparative effect estimate is available to interpret.

The record lists a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a description of this single-group trial’s allocation or evidence of observed power. For time-to-event planning, the stated convention is to report a total number of events; for other outcomes, it is to report participants per arm. No calculated planning values are reported in the registry record. Such illustrations should be read as hypothetical design quantities, not as observed outcomes or proof that a study could detect an effect.

The primary endpoint description identifies Kaplan-Meier methods and an exponential assumption, but the registry record does not give further detail about model fitting, variance estimation, missing observations, protocol deviations, or sensitivity analyses. Those omissions limit independent assessment of the statistical procedure and its robustness. The listed methods establish the intended general approach; without the estimate, interval, and fuller analysis details, they do not reveal what the study found.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, median overall survival, and four secondary outcomes: response rate, clinical benefit rate, progression-free survival, and grade 3 and 4 toxicities. The registry record does not report a multiplicity strategy for interpreting results across these outcomes. In general, when several outcomes are examined, the chance of at least one apparently unusual result can increase if each is assessed independently. Methods for controlling or describing that issue, including any hierarchy among secondary outcomes, are not reported in the registry record.

Missing-data methods are also not reported in the registry record. The primary endpoint is time-to-event, for which incomplete follow-up is generally handled through censoring, but this record does not describe censoring rules, follow-up completeness, or sensitivity analyses. For tumor-response outcomes, the record does not specify how missing scans or unevaluable assessments were handled. It does not describe missingness for toxicity or other outcome data either.

The analysis population is not reported in the registry record. The record does not state whether analyses included all enrolled participants, only those who started treatment, or another defined group. It also does not describe exclusions, protocol deviations, or how participants with no outcome assessment were treated. These details matter because choices about who contributes data and how unavailable measurements are handled can affect estimates and their interpretation.

The registry reports zero analyses, so no outcome-specific analysis results are available there. The record does not report a statistical analysis plan, interim analyses, or sample-size justification. Those items should not be inferred from the stated endpoint method or the separate planning assumptions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypotension (4.0%), febrile neutropenia (2.0%), atrial fibrillation (2.0%), chest pain - cardiac (2.0%), abdominal pain (2.0%).

The safety record lists 50 at risk in the serious adverse-event category and 9 affected. It separately lists 50 at risk and 33 affected in the other adverse-event category. The record also lists 45 deaths. These are registry entries for this treatment group; the record does not provide additional detail about event timing, exposure duration, or how each event was attributed.

The listed serious-event terms are hypotension at 4.0%, febrile neutropenia at 2.0%, atrial fibrillation at 2.0%, chest pain - cardiac at 2.0%, abdominal pain at 2.0%, and mucositis oral at 2.0%. These percentages should be read as the percentages attached to the registry’s event terms, not as comparative risks against another treatment. The registry does not provide a control group for such a comparison.

Adverse-event counts and overall survival answer different questions. The safety entries describe affected counts and specified event terms; overall survival requires the time from treatment initiation to death and its time-to-event analysis. The safety record does not provide that survival estimate. Nor do the entries alone establish that the regimen caused an event. The registry record does not report further attribution or participant-level details.

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

This record describes a completed phase II, single-group study of metformin hydrochloride with FOLFOX in metastatic pancreatic cancer. It identifies median overall survival as the primary endpoint and specifies a Kaplan-Meier approach with an exponential-distribution assumption for estimating the median. It also lists secondary tumor-response, progression-free survival, and toxicity outcomes. These design and endpoint details clarify what the study was intended to examine.

They do not establish the observed result. The registry record does not report the median overall survival, its 95% confidence interval, or results for the listed secondary outcomes. Although it records 45 deaths, that count is not a substitute for the time-to-event estimate: it does not show when deaths occurred, how much follow-up was available, or the estimated survival distribution. The completed status likewise indicates trial status, not a positive or negative outcome.

The single-group design cannot directly establish whether outcomes differ from those under another treatment. Without a concurrent control group, the registry record does not support a randomized causal comparison. The safety entries provide counts and listed event percentages, but not comparative risk, and they do not by themselves establish that the regimen caused those events.

Accordingly, the record supports a description of the study’s design, planned endpoint, treatment regimen, and selected safety entries. It does not support a conclusion about the magnitude, precision, or comparative meaning of the primary endpoint. It also does not report enough analysis detail to assess missing data, multiplicity, or robustness of the planned methods. Those limits apply whether the intended clinical question concerns survival, tumor response, or toxicity.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and its analysis method matter. Overall survival is anchored to a specified starting point—the first day of treatment—and an event defined as death from any cause. The registry’s use of a time-to-event method acknowledges that participants may have differing follow-up. Its additional exponential assumption is important because it constrains the modeled event pattern over time.

The trial’s single-group design is also central to interpretation. A treatment group’s outcomes can be described, but a comparator is needed to estimate a direct treatment contrast. Recognizing this distinction prevents descriptive results from being mistaken for evidence of comparative effect. The record’s completion status and enrollment figure describe the trial, but they do not answer whether its treatment outcomes differ from another approach.

The missing posted outcome analyses make another statistical point: a planned endpoint is not a result. Without the median and confidence interval, readers cannot assess the estimate’s magnitude or precision. Without secondary outcome results, the listed outcomes cannot be interpreted as observed findings. Planning illustrations based on an observed effect are also distinct from the trial’s actual design and cannot be treated as observed power.

Finally, safety counts require context. Serious-event and other-event entries summarize reported categories, while time-to-event outcomes depend on timing and follow-up. Separating these forms of evidence—and keeping descriptive findings apart from causal comparisons—is essential to a careful reading of a single-group clinical study.

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 principal limitation for interpreting outcomes is that the registry record does not report the primary endpoint estimate or results for the secondary outcomes. It also reports zero analyses. The study is marked completed, but without posted outcome analyses the record cannot establish the observed survival distribution, response outcomes, progression-free survival, or toxicity results beyond the listed safety entries.

The design is single-group, with allocation recorded as not applicable and no masking. No concurrent comparator is described. As a result, outcomes in the treatment group cannot be directly contrasted with outcomes under another regimen within this trial. The record does not report a comparative effect estimate or sponsor hazard ratio.

The registry identifies Kaplan-Meier methods and an exponential assumption for estimating median overall survival, but it does not report diagnostic information or sensitivity analyses to assess that assumption. Censoring details, follow-up completeness, analysis populations, missing-data procedures, multiplicity methods, interim analyses, and a statistical analysis plan are not reported in the registry record. These gaps limit assessment of the estimation process and of how other outcomes were handled.

The treatment description includes a clause about continuing in the absence of disease progression or unacceptable toxicity, but its recorded wording is incomplete. The registry record does not report additional detail to resolve the omitted text. The listed adverse-event entries also lack timing, exposure context, and further attribution information. These limitations restrict interpretation of the posted record; they should not be treated as evidence for or against a treatment effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer — NCT01666730.
• Registry record last updated 2021-08-10; status last verified 2021-07.
• Results first posted 2021-08-10.
• 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

The registry describes a phase II, completed, single-group study of metformin hydrochloride with modified FOLFOX 6 in metastatic pancreatic cancer. Enrollment is listed as 50. The primary endpoint is median overall survival from the first day of treatment to death from any cause, assessed up to 1 year. The planned method is Kaplan-Meier estimation, with the median estimated assuming an exponential distribution and a 95% confidence interval.

Secondary outcomes include response rate, clinical benefit rate, progression-free survival, and grade 3 and 4 toxicities. The registry lists serious and other adverse-event counts and selected serious-event terms. It does not report the primary or secondary outcome analyses, a comparator, or a statistical analysis plan. The posted record therefore describes the study’s design and intended outcomes but does not provide the results needed to assess the primary endpoint or comparative effects.