Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy (NCT02569723), a na na study. The primary outcome is Feasibility of 14C Oxaliplatin Microdose as a Clinical Assay to Predict Oxaliplatin Exposure.

2. Clinical Question

The central statistical question is whether a low-dose assay can serve as a useful predictor of exposure during oxaliplatin-based treatment. This is a within-participant predictive question, rather than a treatment-effect question comparing two groups. The primary endpoint concerns exposure, not whether the chemotherapy improves a clinical outcome.

The study title and summary also describe interest in sensitivity to oxaliplatin-based chemotherapy and individualized dosing. The listed secondary outcomes include duration of disease control according to RECIST 1.1 and response rate according to RECIST 1.1. These outcomes address clinical disease status, but they do not replace the primary exposure-correlation question. The registry record does not report results for these outcomes or establish how they were intended to connect to the microdose assay.

The pilot enrolled 6 participants, so any predictive relationship would need to be interpreted with attention to the small amount of information available. The record does not report a primary endpoint estimate, uncertainty interval, or analysis result. It therefore does not establish from the posted results whether microdose exposure predicted therapeutic exposure in these participants.

3. Trial Design

This was a completed, single-group pilot study sponsored by Edward Kim. The registry records the study as phase NA, with allocation NA and no masking. Enrollment was 6. The listed condition is colon adenocarcinoma, and the study summary describes patients with colorectal cancer that has spread to other parts of the body.

Participants received carbon C 14 oxaliplatin as a microdose through an intravenous infusion over 120 minutes. The registry states that, beginning not more than 4 weeks after the initial microdose, participants received FOLFOX6. The recorded treatment description names intravenous leucovorin calcium and fluorouracil, including a fluorouracil infusion over 2 hours and a longer ambulatory infusion. The treatment description is incomplete in the registry record, so the full regimen details cannot be established from that description.

The primary outcome is the feasibility of using the 14C oxaliplatin microdose as a clinical assay to predict oxaliplatin exposure. Its stated measure is R squared, based on correlating the area under the curve from phase 0 microdosing with the area under the curve for a therapeutic oxaliplatin dose. The recorded measurement schedule starts with predose sampling and includes time points through 24 hours after the microdose.

The record lists four outcome measures in total, including secondary measures of disease control duration, adverse events, and response rate. It records the study as completed, with a start date of 2015-10-16 and primary completion date of 2018-04-20. Completion status and dates indicate the administrative status of the trial; they do not supply evidence about the size or precision of the primary relationship. The registry record does not report a randomized control group, masking, a statistical analysis result, or a detailed statistical plan.

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

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 Feasibility of 14C Oxaliplatin Microdose as a Clinical Assay to Predict Oxaliplatin Exposure, measured over 0-5 minutes predose, 5, 15, and 30 minutes, and at 1, 2, 4, 8, and 24 hours after carbon C 14 oxaliplatin microdose.

The primary endpoint is intended to quantify how closely exposure measured after a carbon C 14 oxaliplatin microdose corresponds to exposure after therapeutic-dose oxaliplatin. Exposure is represented by the area under the concentration-time curve, or AUC. The registry specifies R squared as the endpoint measure and describes correlating the microdose AUC with the therapeutic-dose AUC.

As a general statistical explanation, AUC condenses concentration measurements across time into an overall measure of exposure. A relationship between the two AUC measurements would indicate whether participants with relatively higher microdose exposure also tend to have relatively higher therapeutic-dose exposure. R squared describes how much variation in one measure is accounted for by a fitted relationship with the other; its interpretation depends on the analysis model and data.

This endpoint is used because the assay is intended to predict therapeutic exposure from a microdose measurement. It is not itself a measure of tumor response, disease control, toxicity, or survival. The record’s stated sampling schedule includes 0-5 minutes predose, 5, 15, and 30 minutes, and 1, 2, 4, 8, and 24 hours after the microdose. It does not report the observed R squared, the fitted relationship, an uncertainty interval, or the corresponding therapeutic-dose exposure results. Therefore, the endpoint’s planned meaning can be described, but its empirical performance cannot be judged from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary endpoint uses R squared to evaluate the relationship between two exposure measurements: AUC after the carbon C 14 oxaliplatin microdose and AUC after therapeutic-dose oxaliplatin. The registry also specifies repeated sampling after the microdose, from predose through 24 hours. These measurements are intended to describe exposure over time, rather than a single concentration at one time point.

What does R squared describe?

As a general statistical concept, R squared describes how much of the variation in an outcome is accounted for by a fitted model. In a simple linear setting, it is commonly interpreted in relation to the strength of the linear fit. It is not, on its own, a complete description of prediction quality. It does not show whether predicted and measured values agree closely in absolute terms, whether the relationship is biased, or how much an individual prediction might vary. Those questions require further results and methods that are not reported in the registry record.

The record labels the endpoint as feasibility of the microdose assay to predict exposure and gives R squared as its measure. It describes correlating the phase 0 microdose AUC with the therapeutic-dose AUC. This description does not specify the exact regression model, how AUC values were estimated, how missing concentration samples would be handled, whether transformations were considered, or how uncertainty was calculated. Those details are not reported in the registry record.

Why does the within-participant design matter?

Each participant is intended to contribute a microdose measurement and a later therapeutic-dose measurement. Comparing paired measurements can control for some stable differences between participants because each person is compared with their own later value. In general, however, pairing does not remove variation caused by changes over time, measurement error, or differences between the microdose and therapeutic-dose conditions. The interval allowed between doses is described as beginning not more than 4 weeks after the microdose. The record does not explain how the interval or other participant-level factors were handled in the analysis.

This is not a randomized comparison between two groups receiving different treatments. Allocation is recorded as NA, masking as none, and the model as single group. Accordingly, the primary question is about association between two measurements, not a causal contrast between assigned interventions. The registry record does not report any adjustment strategy or covariates for the exposure analysis.

What can a small pilot estimate establish?

In general, pilot studies can explore feasibility and generate preliminary estimates, but a small sample tends to leave substantial uncertainty about the size and stability of an association. The enrollment was 6. The record does not report a confidence interval or other uncertainty measure for the primary endpoint, so the precision of the assay relationship cannot be evaluated. A numerical estimate, even if one were available, would need to be considered alongside its uncertainty and the intended use of the assay.

The registry record includes a planning description for sample-size illustrations based on fractions of an observed effect, with a two-sided significance level of 0.05 and equal allocation between two arms under a normal approximation. That general planning framework does not describe the actual single-group study design, and no numerical illustration is reported in the registry record. Planning calculations are not observed study results and do not establish the power of the completed study.

What is not available for appraisal?

The record lists four outcome measures and no analyses. It does not report the primary R squared result, a confidence interval, a p-value, participant-level exposure values, or a prespecified analysis procedure. It also does not report whether there were interim analyses, a sample-size justification for the enrolled pilot, a method for handling missing data, or an analysis population definition. The statistical plan is not reported in the registry record.

As general guidance, an analysis of a predictive assay would ordinarily be interpreted using more than a single measure of association. Relevant considerations can include the fitted relationship, uncertainty, agreement between predicted and measured values, and performance in new participants. These are methodological considerations, not methods documented for this trial. The registry record does not state that any such analyses were performed.

The key distinction is between a registered aim and an empirical result. The endpoint description tells the reader what the investigators intended to compare. Without the estimate and its uncertainty, the posted record does not establish whether microdose AUC predicted therapeutic-dose AUC, or how reliable such predictions might be.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, with the primary measure focused on the relationship between microdose and therapeutic-dose oxaliplatin exposure. Listed secondary measures include duration of disease control according to RECIST 1.1, participants with adverse events according to CTCAE Version 4, and response rate according to RECIST 1.1. The record does not report results for these outcomes or describe a strategy for controlling the risk of false-positive findings across multiple outcomes. A multiplicity plan is not reported in the registry record.

The record also does not report how missing measurements or incomplete follow-up were handled. For an exposure relationship, missing samples at one or more of the stated collection times could affect AUC estimation; this is a general methodological issue, not a reported event in this trial. Whether any samples or outcome observations were missing is not reported in the registry record.

An analysis population definition is also not reported in the registry record. The enrollment count is 6, but the record does not specify how many participants contributed usable paired AUC measurements or were included in each outcome analysis. No analysis results are listed, and the record reports zero analyses.

Without a stated multiplicity approach, missing-data procedure, or analysis population, the statistical interpretation of any outcome result would require additional documentation. Since the primary result itself is not reported, these omissions chiefly limit assessment of how the planned analysis would have been carried out and how complete the underlying data were.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry records one group titled Carbon C 14 Oxaliplatin and Oxaliplatin, with 6 participants at risk for serious adverse events and 0 participants affected by serious adverse events. It also records 6 participants at risk for other adverse events and 3 participants affected by other adverse events. The record lists 6 deaths in the group.

These are participant counts, not descriptions of event severity, cause, timing, or relationship to treatment. The registry does not identify the causes or timing of the deaths, or whether they were considered related to the study interventions. The serious adverse event count of 0 should be read as the recorded count for this group, not as evidence that no harm was possible or that risk was absent.

The record lists no top serious adverse event terms. It does not provide event-level details in the information recorded for these figures. With 6 participants, the safety counts describe a very small group and cannot characterize uncommon events reliably. The posted counts should therefore be interpreted descriptively and separately from the primary exposure-assay question. They do not establish a causal relationship between any intervention and the reported events.

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

The record documents a completed pilot study intended to evaluate whether exposure after a carbon C 14 oxaliplatin microdose could predict exposure after therapeutic-dose oxaliplatin. The primary measure was specified as R squared for the relationship between the two AUC measurements. The enrolled group contained 6 participants, and the design was single group rather than a randomized comparison.

The central result needed to answer the registered primary question is not reported in the registry record. There is no posted R squared value, correlation estimate, confidence interval, p-value, or account of the primary analysis. Consequently, the record does not establish whether the microdose assay predicted therapeutic exposure, how strong any relationship was, or how precisely it was estimated.

The trial’s rationale refers to predicting sensitivity and supporting individualized dosing, and the listed secondary outcomes include response rate and duration of disease control. Those aims should be distinguished from the primary exposure endpoint. A relationship between two exposure measures would not by itself show that a dosing approach improves clinical outcomes. The registry record does not report results that would establish such a clinical benefit or demonstrate that individual dosing decisions based on the assay are accurate.

The safety figures report no participants with serious adverse events, 3 participants with other adverse events, and 6 deaths in the group. They do not provide enough detail to determine cause, timing, or attribution. These counts describe the registry record; they do not by themselves establish whether an event was related to the microdose or chemotherapy.

In short, the registry establishes the study question, design, enrollment, outcome definitions, and some safety counts. It does not report the primary efficacy-of-assay result or the analyses needed to assess predictive performance. Any stronger conclusion would require results and methods not reported in the registry record.

13. Why This Trial Matters Statistically

This study addresses a statistical problem that arises when a small diagnostic exposure measurement is intended to predict exposure during a later therapeutic dose. The relevant question is not simply whether the two measurements are associated, but whether the relationship is sufficiently precise and informative for its intended predictive use. The registry identifies this aim through an AUC-to-AUC relationship measured with R squared.

The design is useful to distinguish from a conventional treatment comparison. Participants were not allocated to parallel treatment groups; the planned comparison is between two measurements in the same participants. That structure makes the study a pilot of an assay concept, rather than a randomized test of whether one treatment strategy is better than another.

The study also illustrates the difference between a registered endpoint and a reported result. Defining a primary measure and collection schedule clarifies what an investigation intends to assess, but does not show what the data demonstrated. The record gives the primary endpoint’s definition and the enrollment of 6, but no analysis result or uncertainty estimate. Statistical interpretation therefore depends on recognizing what is documented and what is unavailable.

More broadly, an association measure does not answer every question about prediction. As a general principle, prediction requires attention to uncertainty, agreement, calibration, and performance in the population where the assay would be used. The registry record does not report those assessments. The small pilot enrollment also makes precision an important consideration, although the record gives no interval with which to quantify it.

The trial matters statistically because it frames a measurable predictive question while showing why transparent reporting of estimates, methods, and uncertainty is essential. Without those results, the study’s completed status cannot be interpreted as evidence that the assay did or did not predict therapeutic exposure.

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 interpretation is that the registry record does not report the primary endpoint result. The planned R squared measure is identified, but no value, uncertainty interval, p-value, fitted relationship, or participant-level data are reported. This prevents assessment of the magnitude, precision, or predictive usefulness of the relationship.

Enrollment was 6, which limits the information available for evaluating an association and makes any estimate potentially sensitive to individual observations. This is a general concern for a small study; the registry does not provide estimates that would show how it affected this particular analysis. The record also does not report how many participants had complete paired exposure measurements.

The study was single group, with no randomized control group and no masking. Those design features are consistent with an exploratory within-participant assay evaluation, but they do not support a randomized treatment-effect comparison. The registry does not report whether the analysis adjusted for participant characteristics, timing, or other factors.

The statistical analysis plan, sample-size justification, missing-data procedures, analysis populations, and approach to multiplicity are not reported in the registry record. The registry lists secondary clinical outcomes, but their results are not reported. The treatment description is incomplete, so full regimen details cannot be reconstructed from the record.

Finally, safety reporting is limited to group counts. The record reports 6 deaths but does not give their causes, timing, or relationship to study interventions. These limitations mean that the record can support description of the study design and recorded counts, but not a complete evaluation of assay performance, clinical outcomes, or safety attribution.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy — NCT02569723.
• Registry record last updated 2021-03-30; status last verified 2021-03.
• Results first posted 2021-03-30.
• 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

NCT02569723 is a completed, single-group pilot study of a carbon C 14 oxaliplatin microdose assay in advanced colorectal cancer. The record lists 6 enrolled participants, no masking, and phase NA. The primary endpoint is R squared for the relationship between microdose AUC and therapeutic-dose oxaliplatin AUC, with microdose sampling specified through 24 hours.

The record lists secondary outcomes for disease control duration, adverse events, and response rate. It reports 0 participants with serious adverse events, 3 with other adverse events, and 6 deaths in the group of 6; causes and attribution are not reported. Although the study is marked completed, the registry record does not report the primary endpoint result, analysis estimates, or uncertainty measures. Its documented design and counts therefore do not establish the predictive performance of the assay.