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 Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer (NCT01515046), a na phase 2 study. The primary outcome is Overall Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01515046 |
| Phase | Phase 2 |
| Condition | Pancreatic Neoplasms, Pancreatic Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Joseph J. Cullen |
| Results posted | Yes |
2. Clinical Question
The registry describes a phase II study asking whether adding high-dose ascorbate, or vitamin C, to gemcitabine could increase survival for people with advanced pancreatic cancer. Its stated hypothesis is that ascorbate is well tolerated and increases cancer-treatment effectiveness, lengthening survival. The primary outcome is overall survival, defined as time from cycle 1 day 1 to death and measured in days, with follow-up described as up to 5 years.
Population
People with advanced pancreatic cancer, described in the registry as metastatic and node-positive pancreatic cancer. The record lists enrollment of 1.
Intervention
Gemcitabine with escalating intravenous ascorbate. The arm description lists gemcitabine at 1000 mg/m2 weekly for three weeks followed by one week off, and ascorbate twice weekly with escalating doses.
Comparator
No separate control arm is described. The study is registered as a single-group trial, with allocation listed as NA.
Primary question
Overall survival was the primary outcome. The registry record does not report an estimated survival time or a treatment comparison.
This design can describe observations made in the treated group, but it cannot directly establish how those observations compare with outcomes under gemcitabine alone or another control condition. The record also lists progression-free survival, drug-related adverse events per cycle, F2-isoprostane levels, and ascorbate levels as secondary outcomes. Their presence identifies additional questions of interest, but it does not supply results for those outcomes.
3. Trial Design
The registry identifies NCT01515046 as a phase II trial titled Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer. Its official title names the study as PACMAN, a phase II trial of pharmacological ascorbate for metastatic and node-positive pancreatic cancer. The sponsor is Joseph J. Cullen. The record gives a start date of 2012-09 and a primary completion date of 2015-07, and marks the study status as terminated.
The design is listed as single group, with allocation recorded as NA and masking as none. The intervention is gemcitabine with escalating ascorbic acid. The arm description specifies gemcitabine at 1000 mg/m2 weekly for three weeks followed by one week off, and ascorbate twice weekly with escalating doses; it states that week 1 used 15 grams per infusion for two infusions. The registry description ends before giving the subsequent escalation schedule, so further dosing details are not reported in the registry record.
Enrollment is listed as 1. Because the design has no concurrent control group, it is not a randomized comparison and does not provide a like-for-like control comparison. Any observed clinical course in the treated group would need to be interpreted descriptively rather than as an estimate of the causal effect of adding ascorbate. The registry record does not report a protocol-level sample-size justification or explain why enrollment was 1. It also does not report why the study was terminated.
The record lists overall survival as the primary outcome and several secondary outcomes. Although these outcomes indicate what the study intended to assess, the registry does not include statistical analyses for them. In particular, it does not provide an overall-survival estimate, a treatment-effect estimate, or results for the secondary outcomes.
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 | Gemcitabine With Escalating IV Ascorbate |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
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 | Gemcitabine With Escalating IV Ascorbate |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| 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 | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival, measured over up to 5 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | days |
| Endpoint classification | not reduced to a single comparison |
Overall survival measures the time from a defined starting point until death. In this trial, the registry defines the starting point as cycle 1 day 1 and expresses the time in days, with the outcome timeframe stated as up to 5 years. Overall survival is a time-to-event outcome: the event is death, and the measure reflects how long participants remain alive after the specified starting point.
This endpoint is often used in cancer studies because it is a direct, clinically interpretable outcome. It does not rely on deciding whether a tumor has progressed according to imaging criteria, although meaningful analysis still requires clear rules for follow-up, censoring, and handling participants whose status is not known at the end of observation. Those analysis details are not reported in the registry record.
The record names overall survival as the primary outcome but does not provide an estimated survival time, a survival curve, a confidence interval, or an analysis method. The death count in the adverse-event information is not an overall-survival analysis: it does not by itself describe time to death, follow-up, or the distribution of survival times. No survival result can therefore be inferred from the endpoint definition or from the adverse-event counts alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study with enrollment of 1, a single-group design, and no reported statistical analyses. It does not provide an estimate of overall survival or results for the listed secondary outcomes. The central statistical conclusion is therefore limited: the record specifies what the study intended to investigate, but it does not report an analyzed outcome from which the effect of the regimen can be estimated.
The study's stated question concerns survival with gemcitabine plus escalating ascorbate. However, a single treated group cannot show what would have happened to comparable participants under a different treatment condition. Even if an outcome were reported for the treated group, a comparison with an external expectation would be vulnerable to differences in patient characteristics, disease course, and care. The registry identifies no randomized control group, so it cannot support a like-for-like treatment contrast.
Enrollment of 1 also means that any individual clinical course would be highly influential in a group-level description. General statistical reasoning is that very small groups provide little information about the range of outcomes in the intended population. They cannot establish a stable estimate of typical survival or reliably characterize uncommon events. The record does not report a survival estimate, uncertainty interval, or analysis population that could quantify precision.
The adverse-event information lists 1 participant at risk for serious adverse events and 0 with serious adverse events; it also lists 1 at risk for other adverse events and 1 with other adverse events, with 1 death. These are counts in the adverse-event record. They do not establish whether the death was caused by the disease, treatment, or another reason, nor do they reveal when an event occurred. A count of zero for serious events in this record should not be interpreted as evidence that the regimen has no serious risks.
The registry marks the trial as terminated, but does not state why. The record gives no analysis results, reasons for termination, or explanation of whether planned enrollment or follow-up was completed. The posted information therefore cannot determine whether the study stopped early, whether the listed participant completed follow-up, or whether any results were analyzed outside the registry record.
9. Statistical Methods Explained
Statistical methods determine how observations are translated into estimates and how much uncertainty surrounds those estimates. The registry record identifies the primary outcome and design, but it does not report the analysis methods used. The concepts below explain what would generally be relevant; they should not be read as a description of methods actually applied in this trial.
What does a single-group design estimate?
A single-group study observes outcomes among participants receiving the study regimen. It can describe what happened in that group, provided outcome data and follow-up are reported. It does not, by itself, estimate the difference between the regimen and a control treatment. To interpret an outcome causally, researchers need a credible comparison that addresses what would have happened to similar participants under another condition. Random allocation is one way to make such groups comparable, but this registry lists allocation as NA and the model as single group.
Without a concurrent comparator, a survival duration cannot be attributed to the intervention simply because it occurred after treatment began. Disease severity, other care, and participant characteristics may also affect outcomes. External historical comparisons can sometimes be explored, but they are not a substitute for a control group unless comparability and limitations are carefully addressed. No external comparison or adjusted treatment-effect analysis is reported in the registry record.
How are time-to-event outcomes analyzed?
Overall survival is a time-to-event outcome because it combines information about whether the event occurred with the time until it occurred. In general, survival analysis can include participants whose event has not been observed by the end of follow-up, or whose follow-up ends for another reason, by treating their observation as censored at the last known time. This approach depends on accurate event dates and clear censoring rules. The registry defines the time origin and event but does not report censoring rules, follow-up completeness, a survival curve, or a survival model.
A survival curve generally describes the estimated probability of remaining event-free over follow-up. A median survival time, when estimable, is the time at which the estimated survival probability reaches a specified point. Such summaries require outcome and follow-up data; neither a curve nor a median is reported. A single death count cannot substitute for them because it does not show the timing of the event or how long participants were observed.
What does a confidence interval communicate?
In general, a confidence interval expresses the precision of an estimate under the assumptions of the statistical method. A narrow interval indicates less statistical uncertainty than a wide interval, though it does not address every source of bias. With limited observations, estimates are typically imprecise, and the data may be compatible with a broad range of possible outcomes. No confidence interval for overall survival or any other outcome is reported in the registry record, so precision cannot be assessed from the posted results.
What role do event counts play?
For time-to-event studies, the number of observed events is often more directly informative about statistical information than enrollment alone. In general, more observed events can improve precision for survival comparisons, but the benefit depends on study design, follow-up, and the analysis plan. Here there is no reported survival analysis, and the adverse-event death count does not provide the time-to-event data needed to assess the primary endpoint. The record does not report a total event summary for an overall-survival analysis.
How should the planning assumptions be read?
The record describes sample-size planning illustrations based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions, not evidence that the actual trial had two arms: the registered study is single group. The illustrations are not observed power, and they do not establish that the trial was designed or conducted according to those hypothetical assumptions. The registry does not report a trial-specific sample-size justification or the outcome estimates needed to interpret a planning illustration as a feasible or informative design.
For any planned study, sample-size calculations depend on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and desired power. If those assumptions differ from the data-generating conditions, the achieved precision can differ from the plan. A planning number is not a guarantee of a particular result. In this record, the single-group structure and lack of reported outcome estimates prevent a direct interpretation of a two-arm planning framework as evidence about the trial's own ability to answer its clinical question.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists overall survival as the primary outcome and identifies progression-free survival, drug-related adverse events per cycle, F2-isoprostane levels, and ascorbate levels as secondary outcomes. Having multiple outcomes raises the general issue of multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase. Statistical plans may address this by specifying a primary hypothesis, adjusting comparisons, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, hypothesis-testing sequence, or results for these outcomes.
The record also does not report how missing outcome data were handled. For survival analysis, relevant information would include the last known follow-up time, whether vital status was obtained, and how censoring was defined. For other outcomes, the analysis would need to describe which measurements were available and whether missingness was addressed. These details are not reported in the registry record.
Analysis populations are also not described. The record does not say whether analyses were planned for all enrolled participants, participants who began treatment, or another defined group. It gives no participant flow or account of exclusions from analysis. Enrollment is listed as 1, but without an analysis population and outcome data, the number enrolled alone does not establish who contributed to each endpoint analysis.
The registry records zero analyses. Consequently, there is no posted analysis from which to evaluate multiplicity adjustment, missing-data handling, or adherence to a prespecified analysis population.
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 |
|---|---|---|---|
| Gemcitabine With Escalating IV Ascorbate | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Gemcitabine With Escalating IV Ascorbate | 1 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Gemcitabine With Escalating IV Ascorbate | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Gemcitabine With Escalating IV Ascorbate |
|---|---|---|
| Anemia, grade 1 | Investigations | 1 of 1 |
| white blood cell count, decreased, grade 1 | Investigations | 1 of 1 |
| Lymphocyte count decreased, grade 2 | Investigations | 1 of 1 |
| neutrophil count decreased, grade 3 | Investigations | 1 of 1 |
| platelet count decreased, grade 3 | Investigations | 1 of 1 |
| Alanine aminotransferase increased, grade 1 | Investigations | 1 of 1 |
The adverse-event record lists the Gemcitabine With Escalating IV Ascorbate group with 1 at risk for serious adverse events and 0 with serious adverse events. For other adverse events, it lists 1 at risk and 1 affected. It also lists 1 death. These are registry counts, not estimates of event rates or comparisons between treatments.
The group is single-arm, and enrollment is listed as 1. The counts therefore offer very limited information about the frequency or range of harms. A zero serious-event count does not establish that serious events cannot occur, and the record does not report the observation period used for these counts. The presence of an other adverse event does not, on its own, indicate its severity, clinical importance, or relation to treatment.
The death count should be read separately from the serious and other adverse-event counts. The record does not state whether the death was attributed to cancer, treatment, or another cause, or whether it was considered an adverse event. It also does not provide a time-to-death analysis. No serious adverse-event terms are listed in the record, which does not provide further detail about specific events.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, single-group study of gemcitabine with escalating intravenous ascorbate was registered for advanced pancreatic cancer. It specifies overall survival as the primary outcome, measured in days from cycle 1 day 1, and records enrollment of 1. It also lists secondary outcomes and adverse-event counts. These registry entries describe the study framework and the information entered into the registry.
The record does not report an overall-survival estimate, a comparison with a control group, or analyses of the secondary outcomes. It therefore does not establish whether the regimen lengthened survival, changed progression-free survival, altered biomarker levels, or affected adverse events. The death count in the safety information is not an estimate of survival and cannot answer the primary question.
The absence of a comparator is important even apart from the limited enrollment. An outcome observed after treatment cannot show what would have happened under another treatment condition. The registry's single-group design offers no randomized contrast, and the posted record contains no adjusted or external comparison that could address this limitation.
The safety counts are also too limited to characterize risk reliably. Zero serious adverse events in the record should not be interpreted as proof of safety, while the listed other adverse event and death do not establish a treatment relationship. The record does not give event descriptions or causal assessments sufficient to interpret these counts further.
In short, the posted information describes a clinical question and a study design, but it does not provide analyzed efficacy results. It cannot support a conclusion that the regimen does or does not improve survival, and it cannot establish a definitive safety profile.
13. Why This Trial Matters Statistically
This trial is statistically important to read as a design-and-record question rather than as a reported efficacy result. Its primary endpoint is overall survival, an outcome that requires both event status and follow-up time for meaningful analysis. Yet the registry record does not include a survival estimate, an uncertainty measure, or an analysis method. Recognizing the difference between an endpoint definition and an endpoint result prevents the study's stated objective from being mistaken for evidence that the objective was achieved.
The single-group design is another central feature. Without a control group, the study cannot directly estimate the contrast between gemcitabine with ascorbate and an alternative condition. This remains true even when the outcome is clinically meaningful. Statistical analysis cannot create a randomized comparison that the design did not include.
Enrollment of 1 illustrates why reported counts must be interpreted with restraint. A count can be accurate as a registry entry while still providing too little information to characterize outcomes across a patient population. The adverse-event information is useful as a description of what the record lists, but it is not a stable estimate of event frequency or a comparison of treatment risks.
Finally, the record's terminated status, absence of posted analyses, and lack of a reported reason for termination all matter for interpretation. They leave unanswered whether outcome data were analyzed, why the study ended, and how closely the final record reflects the intended study. These gaps do not change the stated research question, but they limit what can be inferred from the registry entry.
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 is that the registry record contains no statistical analyses. Although it names overall survival as the primary endpoint, it does not report survival times, a survival curve, an effect estimate, or uncertainty around an estimate. The listed secondary outcomes likewise have no reported results. The record therefore offers no analyzed evidence with which to answer the study's stated question.
The single-group design has no concurrent control arm, and allocation is recorded as NA. As a result, the design cannot provide a direct randomized comparison. Enrollment of 1 further limits the descriptive information available and makes it impossible to characterize the diversity of outcomes in the intended population from this record.
Important details about outcome ascertainment and analysis are not reported in the registry record. These include survival follow-up completeness, censoring rules, analysis populations, missing-data handling, and any statistical model or hypothesis-testing plan. The registry also does not report a trial-specific sample-size justification or the reason for termination.
The intervention description gives some regimen details, including gemcitabine scheduling and the initial ascorbate dosing, but it does not state the subsequent escalation schedule. The adverse-event record provides counts but not event descriptions, timing, or attribution of the death. These limitations mean the registry data cannot establish treatment effectiveness, explain the death, or define the regimen's safety profile.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer — NCT01515046.
- Registry record last updated 2017-06-08; status last verified 2017-05.
- Results first posted 2017-03-29.
- 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
NCT01515046 is registered as a phase II, single-group study of gemcitabine with escalating intravenous ascorbate for advanced pancreatic cancer. The registry lists enrollment of 1, allocation as NA, masking as none, and status as terminated. It gives a start date of 2012-09 and a primary completion date of 2015-07.
Overall survival, measured in days from cycle 1 day 1 and followed for up to 5 years, is the primary outcome. Secondary outcomes include progression-free survival, drug-related adverse events per cycle, F2-isoprostane levels, and ascorbate levels. The adverse-event record lists 0 serious events among 1 at risk, 1 other adverse event among 1 at risk, and 1 death.
The registry records no analyses and reports no outcome estimates or reason for termination. The single-group design does not provide a concurrent treatment comparison, and the posted information cannot establish an effect on survival or a definitive safety profile.