Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer (NCT01338792), a non-randomized phase 2 study. The primary outcome is Best Overall Response.

2. Clinical Question

3. Trial Design

This was a phase II, non-randomized, single-group study sponsored by the University of Southern California. The registry lists enrollment of 47 and a completed status. The study start is recorded as 2006-06 and primary completion as 2011-12. These dates describe the trial record; they do not provide the timing of individual participants’ treatment or follow-up.

The treatment group received oxaliplatin and pemetrexed disodium. The listed administration was intravenous oxaliplatin over 2 hours and intravenous pemetrexed disodium on day 1. Courses were scheduled to repeat every 21 days for up to 1 year, unless disease progression or unacceptable toxicity occurred. The registry also lists questionnaire administration, laboratory biomarker analysis, reverse transcriptase-polymerase chain reaction, and polymorphism analysis. Further details about how these activities were incorporated into the study are not reported in the registry record.

There was no masking. Because allocation was non-randomized and the study used a single group, the design does not provide a randomized treatment contrast. Outcomes observed during treatment can describe this enrolled group, but they do not by themselves distinguish treatment effects from other explanations, such as the natural course of disease or differences in participant characteristics.

The primary outcome was best overall response. Secondary outcomes included time to disease progression and overall survival, and the number of participants with serious adverse events. The registry lists 3 outcome measures, but it records no analyses. Details of the statistical analysis plan, outcome-specific analysis populations, handling of missing measurements, and any interim analyses are not reported in the registry record. The registry also does not state a sample-size justification or indicate whether the planned enrollment was based on a formal power calculation.

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.

Before assignment: The study had no pre-assignment criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 cycle of treatment were included.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Best Overall Response, measured over RECIST evaluation: Baseline, after every 2 courses, and then every 6 months after off-study, up to 1 year. PSA evaluation: baseline, day 1 of each course, final evaluation, and then every 6 months after off-study, up to 1 year.

Best overall response records the most favorable disease-response category assessed during the specified evaluation period. In this trial, the registry defines response for participants with measurable disease using RECIST 1.0. It describes complete response as disappearance of all target lesions, and partial response as a decrease of at least 30% in the sum of longest diameters of target lesions. Stable and progressive disease are defined by the stated RECIST size-change thresholds. The registry record uses escaped less-than signs in the stable-disease definition; expressed as statistical notation, its thresholds include <30% decrease and <20% increase.

For participants without disease measurable by RECIST, response was based on PSA response. The record defines that as a 50% reduction in PSA confirmed on a second measurement at least 4 weeks later. The endpoint therefore uses different assessment rules according to whether disease was measurable by RECIST. The registry does not report how many participants were assessed under each rule or whether any assessments could not be classified.

Best overall response is used to describe tumor response during a treatment study, rather than to measure the length of time until progression or death. It can provide a clinical activity signal, but a response endpoint does not by itself establish how long a response lasts or whether outcomes differ from what would have occurred without the regimen. The posted numerical result for best overall response is not reported in the registry record. The stated evaluation schedule describes when assessments were intended, not the number or results of completed assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design tell us?

In a single-group study, participants receive the study regimen and outcomes are described within that group. This can characterize what was observed among enrolled and assessed participants. It does not create a randomized contrast with a separate control group. Randomization is useful because it helps make treatment groups comparable with respect to measured and unmeasured characteristics, on average. That protection is absent when the registry describes a non-randomized, single-group design.

For this trial, the response outcome could be described as a count in each response category, or as a proportion if the appropriate denominator were available. Yet the registry does not report those response counts or the number with an evaluable assessment. It is not possible to reconstruct a response estimate from the enrollment figure alone. The enrollment figure and the endpoint population description do not supply the missing outcome numerator or confirm the analysis denominator.

How should response definitions be understood?

RECIST 1.0 classifies changes in measurable lesions using specified size criteria. A category such as partial response represents a threshold-based classification, not a direct measurement of how long a response lasts. The registry also uses PSA criteria for participants whose disease was not measurable by RECIST. That approach allows an outcome definition for participants who cannot be classified through measurable lesions, but the two routes to response are not identical measurements. The registry does not report the count of participants in each assessment route or how the results were combined into best overall response.

Assessments were scheduled at baseline and after every 2 courses, with further RECIST evaluation every 6 months after leaving the study, up to 1 year. PSA evaluations were scheduled at baseline, day 1 of each course, at final evaluation, and every 6 months after leaving the study, up to 1 year. A schedule is not evidence that every planned assessment was completed. The number of observed assessments, any deviations, and the rules used for incomplete follow-up are not reported in the registry record.

What would uncertainty intervals add?

General statistical explanation: an uncertainty interval conveys a range of estimates compatible with the observed data under the assumptions of the analysis. It helps readers see how precisely an effect or proportion has been estimated. A point estimate alone does not reveal that precision. For a binary response outcome, the interval would depend on both the number with the outcome and the denominator assessed. Since neither response counts nor a response estimate are reported in the registry record, response uncertainty cannot be assessed from the posted information.

General statistical explanation: estimates from a single group can have sampling uncertainty even when all outcomes are recorded. That uncertainty concerns how the observed group may differ from the broader population represented by the study. It is distinct from uncertainty about causal attribution. A narrow interval around a single-group estimate would not, on its own, remove the limitations created by the absence of a randomized comparator.

Why does the analysis population matter?

The record says that participants who received at least 1 cycle of treatment were included for the primary outcome. That is a population definition, but further analysis details are absent. It does not state the number who received treatment, how participants with missing response measurements were handled, or whether participants who discontinued treatment remained in the primary analysis. Such details matter because excluding participants with unavailable assessments can change the denominator and can introduce bias if missingness is related to disease status or treatment experience.

The registry lists time to disease progression and overall survival as secondary outcomes. Time-to-event methods account for the fact that participants can have different lengths of follow-up and that some may not have experienced the event by the end of observation. General statistical explanation: censoring records that an event has not been observed during a participant’s available follow-up; interpreting a time-to-event estimate then depends on assumptions about the censoring process and the analysis method. The specific definitions of progression and survival, censoring rules, follow-up summaries, and statistical methods are not reported in the registry record.

What do the planning assumptions mean?

General statistical explanation: a sample-size calculation asks how much information a future study may need to detect a specified effect under stated assumptions. The planning illustration described for this record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It defines the target effect as a stated fraction of the observed effect. These are planning assumptions, not evidence that the completed trial used that design or was powered according to that calculation. The actual study is recorded as a single-group, non-randomized trial.

The planning assumptions distinguish event-based time-to-event calculations, which report a total number of events, from other calculations, which report participants per arm. The record does not provide the numerical results of those planning calculations in the information available for this analysis. A planning illustration is not observed power and does not establish the probability that the trial detected an effect. The registry does not report a protocol-based sample-size justification or the statistical plan used for the completed study.

Why does over-dispersion matter in general?

General statistical explanation: over-dispersion occurs when observed variation is greater than expected under a model’s assumptions. If a model assumes that outcomes vary less than they actually do, standard errors may be too small and confidence intervals too narrow. The appropriate response depends on the outcome and model, and may involve a model that allows greater variability. The registry record does not report a model for the primary binary outcome or indicate whether over-dispersion was assessed. This concept therefore helps explain a general issue in statistical modeling, but it does not establish a problem in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists best overall response as the primary outcome and time to disease progression, overall survival, and serious adverse events among the secondary outcomes. Multiple outcomes can create multiplicity: when many statistical comparisons are made, the chance of at least one apparently notable result can increase. General statistical explanation: analysts may address this through a prespecified hierarchy, adjusted significance thresholds, or by treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or the inferential status assigned to those outcomes.

The record lists 3 outcome measures and 0 analyses. This indicates that outcome measures are recorded, but no analysis entries are reported in the registry information. It does not show whether analyses were conducted elsewhere, and it does not provide results for the listed efficacy outcomes. The primary response result, its denominator, and any uncertainty interval are not reported in the registry record.

For the primary endpoint, the stated population includes participants who received at least 1 cycle of treatment. The record does not report how many participants met that definition, how missing or unevaluable response assessments were handled, or whether any participants were excluded from the analysis. The evaluation schedule alone cannot answer these questions. Missing data can affect both the denominator and the interpretation of an estimate, particularly when missingness is related to outcome status or treatment discontinuation.

The registry also does not report whether outcome definitions or analysis populations changed during the study, or whether there were interim analyses. These details are not reported in the registry record and should not be inferred from the listed outcome schedule. Without the analysis plan and outcome results, multiplicity, missing-data handling, and analysis-population choices cannot be independently assessed.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphopenia (19.1%), neutrophils/granulocytes (anc/agc) (19.1%), fatigue (asthenia, lethargy, malaise) (14.9%), leukocytes (total wbc) (14.9%), glucose, serum-high (hyperglycemia) (12.8%).

The registry records serious adverse events for 35 of 47 participants at risk in the treatment group. It records other adverse events for 47 of 47 participants at risk. These figures are counts of participants with events in the registry record; they do not establish how many events each participant experienced or how long events lasted. The record does not provide severity grades, timing, treatment relatedness, or event-specific counts beyond the listed serious-event terms.

The most frequently listed serious adverse-event terms are lymphopenia at 19.1%, neutrophils/granulocytes (ANC/AGC) at 19.1%, fatigue (asthenia, lethargy, malaise) at 14.9%, leukocytes (total WBC) at 14.9%, glucose, serum-high (hyperglycemia) at 12.8%, and hemoglobin at 12.8%. These are registry-reported percentages for the named terms. The registry does not give the corresponding participant counts for each term in the information, and it does not describe whether participants could contribute to more than one term.

Safety counts from a single-group study describe events recorded among treated participants. Without a randomized comparator and fuller event details, they do not establish comparative risk or causation. Deaths are not reported in the registry record’s group information. These limitations do not erase the recorded counts; they define what can and cannot be concluded from them.

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

The trial record establishes that a phase II, non-randomized, single-group study evaluated oxaliplatin and pemetrexed disodium together in refractory hormone-resistant prostate cancer. It describes the treatment schedule, the primary response definitions, and selected safety counts. The record’s enrollment figure is 47, and the primary endpoint population is defined as participants who received at least 1 cycle of treatment.

Those details do not establish the magnitude of response. The registry does not report the numerical best overall response result, including response-category counts or an estimate with an uncertainty interval. It also does not provide enough information to determine the endpoint denominator or assess whether response data were missing. Therefore the posted record supports neither a quantitative response estimate nor an assessment of how precisely such an estimate was measured.

The study design also limits causal interpretation. A single-group result cannot be compared with a randomized control group in this record. Outcomes could reflect the regimen, participant characteristics, disease course, or other factors; the available information does not separate those explanations. The inclusion of time to disease progression and overall survival as secondary outcomes does not establish their results, because numerical outcome findings and analysis methods are not reported.

The serious adverse-event figures provide descriptive safety information for the treatment group, but lack the detail needed to assess timing, severity grades, attribution, or comparative risk. They should be interpreted as recorded counts and named event categories, rather than as proof that the regimen caused every event.

In general, statistical evidence is strongest when endpoint definitions, analysis populations, effect estimates, uncertainty intervals, and relevant comparisons are all available. For this registry record, important pieces are missing. The appropriate conclusion is limited to the study’s documented design and the reported safety information, not a conclusion about treatment benefit or lack of benefit.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported numerical result are both necessary for interpretation. The registry gives detailed response rules, including separate assessment approaches for participants with measurable disease and those without measurable disease by RECIST. That information explains what the endpoint was intended to capture. But without the response counts, denominator, or estimate, readers cannot quantify the outcome or its precision.

The design also demonstrates the distinction between describing an outcome and estimating a comparative effect. In a non-randomized, single-group study, outcomes can characterize the treated group, but they do not supply a randomized counterfactual. This distinction remains important even when a study has a defined endpoint and a completed status. Completion does not substitute for outcome reporting or for a comparator when the question is comparative.

The record also gives a useful example of why analysis populations and missing-data procedures matter. The endpoint population is stated as participants who received at least 1 cycle, but the number meeting that criterion and the handling of unevaluable assessments are not reported. Readers cannot safely treat enrollment as the endpoint denominator. Clear reporting of participant flow and missingness would make it possible to understand how the outcome estimate was formed.

Finally, the contrast between named serious-event frequencies and absent efficacy results underscores that different parts of a registry record can have different levels of detail. Safety counts can be described while the primary efficacy result remains unavailable. Statistical interpretation should match the evidence actually reported: precise about documented details, cautious about causal claims, and explicit when key analysis information is not reported in the registry record.

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 efficacy is that the registry record does not report the numerical best overall response result. Without response-category counts, an endpoint denominator, or an uncertainty interval, the response outcome cannot be quantified or assessed for precision. The record defines the primary endpoint population as participants who received at least 1 cycle, but it does not report how many participants met that definition or how incomplete assessments were treated.

The study’s non-randomized, single-group design does not provide a like-for-like control comparison. As a result, observed outcomes cannot be interpreted as a randomized estimate of the regimen’s effect relative to another treatment. The registry identifies secondary outcomes for progression and survival but does not report their numerical results or analysis methods.

Additional design and analysis details are not reported in the registry record, including eligibility criteria beyond the listed conditions, the sample-size justification, the statistical analysis plan, multiplicity handling, interim analyses, and rules for missing outcome data. The different response assessment pathways—RECIST for measurable disease and PSA criteria for participants without RECIST-measurable disease—also mean that the record would need to report how many participants were assessed by each approach and how their results were combined to clarify the endpoint composition.

Safety reporting is limited to participant counts at risk, aggregate affected counts, and selected serious-event terms with percentages. Event timing, severity grades, attribution, duration, and death counts are not reported in the registry record. These omissions constrain interpretation without changing the descriptive figures that are recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer — NCT01338792.
• Registry record last updated 2014-03-10; status last verified 2014-02.
• Results first posted 2013-12-11.
• 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 NCT01338792, a completed phase II, non-randomized, single-group study sponsored by the University of Southern California. It lists enrollment of 47 and investigates oxaliplatin with pemetrexed disodium for refractory hormone-resistant prostate cancer. The treatment schedule specifies intravenous administration on day 1, with courses repeating every 21 days for up to 1 year, subject to disease progression or unacceptable toxicity.

Best overall response was the primary outcome, assessed using RECIST 1.0 for measurable disease and PSA criteria for participants without RECIST-measurable disease. Time to disease progression, overall survival, and serious adverse events are listed as secondary outcomes. The numerical primary response result and efficacy analyses are not reported in the registry record.

The safety record reports serious adverse events in 35 of 47 participants at risk and other adverse events in 47 of 47 at risk. The study has no randomized comparator, and the registry does not report the analysis plan, missing-data handling, or sample-size justification.