A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer (NCT01619423), a randomized phase 1, phase 2 study. The primary outcome is Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia).

2. Clinical Question

The trial was designed to assess whether pretreatment with PledOx changes the frequency and severity of FOLFOX6 side effects, while also assessing efficacy when PledOx is added to first-line chemotherapy. The posted primary outcome is specifically about neuropathy at a defined severity threshold; it is not a general measure of every possible side effect or of cancer control.

The results compare placebo with three PledOx groupings: 2 µmol/kg, 5+10 µmol/kg, and 2+5+10 µmol/kg. Those groupings reflect the distinct randomized parts described in the record. The dose-escalation part was open and is described separately; it should not be conflated with the randomized primary-outcome comparisons.

3. Trial Design

NCT01619423 is recorded as a randomized, triple-masked, parallel-group study, with phase listed as PHASE1 and PHASE2. The title describes a double-blinded, randomized three-armed phase II trial, while the registry entries describe multiple parts: an open dose-escalation part and randomized parts 2a and 2b. Part 1 studied dose escalation and had no planned outcomes according to the record. The randomized parts used differing dose groups, so the overall design is more nuanced than a single three-arm comparison.

The registry lists enrollment as 186. The primary outcome compares placebo with a 2 µmol/kg group, a combined 5+10 µmol/kg group, and a combined 2+5+10 µmol/kg group. These are the posted analysis groups; they do not imply that each dose was tested in every randomized part. The record describes part 2a as assigning placebo, 2, or 10 µmol/kg, and part 2b as assigning placebo, 2, or 5 µmol/kg.

The intervention groups received PledOx with FOLFOX6, a combination of folinic acid, 5-fluorouracil, and oxaliplatin. The comparator received placebo with FOLFOX6. The registry identifies the primary-outcome population as the full analysis set and gives the outcome timeframe as every second week during cycle 1-8, for up to 16 weeks.

The study began in 2012-09, reached primary completion in 2016-03, and has completed status. The protocol’s original sample-size justification, the rationale for the particular allocation across groups, and further details of how the randomized parts were combined for analysis are not reported in the registry record.

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: 186 participants were enrolled and 186 started the study, however, two patients had too high basal manganese levels (detected after first treatment cycle) and were excluded from further treatment (screening failures) but are part of the safety population. 184 patients are part of the treatment population (11 in part 1 and 173 in part 2)

Part 1 (Dose Escalation)

Reasons for not completing this period:

Part 2a

Part 2b

Analysis population for the primary outcome, as defined in the registry: Full analysis set

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: Although no pre-specified Outcome Measures were performed on participants in Part 1, however, baseline data for all 186 participants is reported.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia), measured over Every second week during cycle 1-8, for up to 16 weeks.

The primary endpoint counts participants who experienced neuropathy grade 2 or higher, specifically paraesthesia or dysaesthesia assessed using the Oxaliplatin Specific Sanofi Scale criteria. The registry describes the outcome as the percentage of patients meeting that threshold over cycles 1 to 8, with assessments every second week during cycle 1-8, for up to 16 weeks. The posted outcome entries give participant counts and group sizes rather than a percentage as the endpoint value.

A severity threshold turns a graded clinical experience into a binary outcome for analysis: each participant either meets the stated threshold during the assessment period or does not. This can make group comparisons straightforward to interpret as differences in the frequency of participants crossing that threshold. It also means the endpoint does not preserve all detail about symptom intensity, duration, or changes that remain below grade 2. Those details are not included in the posted primary result.

Neuropathy is a relevant outcome in a trial involving oxaliplatin, but the statistical result is limited to the defined symptoms, grading criteria, and observation window. It does not represent all neurological effects, all adverse events, or the overall benefit and harm profile. The registry does not report secondary outcomes in the posted results record, so the primary endpoint cannot stand in for broader efficacy or safety outcomes.

7. Results Posted in the Registry

• FOLFOX6 + PledOx 2 µmol/kg: 19.3% (11/57) versus 23.3% (14/60) on control; risk difference -4.0 percentage points (95% CI -18.9 to 10.8), risk ratio 0.83 (0.41–1.67); unadjusted two-proportion z-test p = 0.595.
• FOLFOX6 + PledOx 5+10 µmol/kg: 10.7% (6/56) versus 23.3% (14/60) on control; risk difference -12.6 percentage points (95% CI -26.0 to 0.8), risk ratio 0.46 (0.19–1.11); unadjusted two-proportion z-test p = 0.072.
• FOLFOX6 + PledOx 2+5+10 µmol/kg: 15.0% (17/113) versus 23.3% (14/60) on control; risk difference -8.3 percentage points (95% CI -20.9 to 4.3), risk ratio 0.64 (0.34–1.22); unadjusted two-proportion z-test p = 0.176.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: it records whether each participant experienced neuropathy grade 2 or higher during the specified period. For a binary outcome, a group’s event proportion is the number of participants with the event relative to the number assessed. The posted arm entries give the event counts and group sizes. The registry describes the endpoint in percentage terms, but the analysis uses the participant counts associated with that threshold.

What does a risk difference describe?

A risk difference subtracts the event proportion in the comparator group from the event proportion in the intervention group. It is expressed on an absolute scale, rather than as a relative change. In the recalculated comparisons, placebo is the reference group and each PledOx grouping is compared with it. A negative estimate means the observed event proportion is lower in the PledOx grouping; a positive estimate would mean it is higher. The estimate alone does not establish that the difference is precise or that it reflects a reproducible treatment effect.

The recalculated estimates use the posted summary counts and are unadjusted. They are not the sponsor’s statistical analysis. An unadjusted comparison does not account for stratification or other covariates unless those are explicitly incorporated in the calculation. The registry identifies the sponsor’s method as Cochran-Mantel-Haenszel, so its odds-ratio results use a different measure and an analysis method that can account for stratification. The stratification factors are not reported in the registry record.

How should the odds ratios be read?

An odds ratio compares the odds of an event between groups. An odds ratio below one indicates lower observed odds in the intervention group relative to the comparator in the analysis, but it is not an absolute risk difference and should not be read as a percentage-point change. The sponsor’s posted odds ratios are 0.78 for 2 µmol/kg, 0.55 for 5+10 µmol/kg, and 0.62 for 2+5+10 µmol/kg. Because these are odds ratios and the recalculated results are risk differences, their numerical values are not directly interchangeable.

The registry’s reported analyses list an upper confidence limit for each odds ratio and a confidence interval percentage of 10, but no lower confidence limit. An interval expresses a range of values compatible with the data under the statistical method and its assumptions. Without a lower limit, the posted record does not give a complete interval for these sponsor estimates. The record does not explain the incomplete interval entries.

Why do methods and assumptions matter?

Statistical methods can differ because they use different effect measures, make different adjustments, and may handle trial structure differently. As a general statistical point, the Cochran-Mantel-Haenszel approach combines information across strata to estimate an association while accounting for stratification. The record does not identify which strata were used, so the specific adjustment cannot be assessed from the posted analysis alone. The unadjusted recalculation, in contrast, is a direct summary-count comparison and should be treated as a descriptive re-analysis rather than a substitute for the sponsor’s analysis.

Uncertainty is also important. A confidence interval describes the range of effect estimates that remain compatible with the data under the method; a broad interval indicates that the data do not pin down the effect closely. A p-value measures how unusual the observed data, or more extreme data, would be under a specified null model. It does not give the probability that the null hypothesis is true, and it does not measure clinical importance. The registry does not report the sponsor’s full analysis plan or the rationale for any particular inferential threshold.

There are three posted PledOx-versus-placebo comparisons. Repeated testing can increase the chance of at least one apparently notable result if no multiplicity approach is used. Whether the sponsor adjusted for multiple comparisons is not reported in the registry record. The unadjusted recalculated p-values should therefore be read as individual comparisons, not as a multiplicity-controlled assessment across the set.

Several additional methodological details are unavailable: how missing primary-outcome assessments were handled, whether outcome assessments were analyzed by randomized assignment, and how the dose groups across parts 2a and 2b were combined beyond the listed comparison groups. The endpoint population is called the full analysis set, but the registry does not define its membership or describe exclusions. These gaps constrain reproduction and interpretation of the analysis. They do not show that any particular analytic choice was made; they mark information that is not reported in the registry record.

10. Confidence Intervals and Precision

The recalculated risk-difference intervals communicate substantial uncertainty around each point estimate. For the 2 µmol/kg comparison, the estimate is -0.040 and the interval runs from -0.189 to 0.108. For the 5+10 µmol/kg comparison, the estimate is -0.126 and the interval runs from -0.260 to 0.008. For the 2+5+10 µmol/kg comparison, the estimate is -0.083 and the interval runs from -0.209 to 0.043. Each interval includes zero, so the posted recalculations do not isolate a risk difference in one direction.

These intervals should not be interpreted as proof that the groups are identical. Rather, they show that a range of differences remains compatible with the data and calculation. The estimates are based on the observed counts in the trial groups, and the size of those groups limits how precisely the underlying event proportions can be estimated. The interval endpoints are not the only consideration: the choice of effect measure, analysis method, and handling of the trial’s parts also matter.

The sponsor’s odds-ratio entries have a separate precision limitation: the registry provides upper limits of 1.5, 1.16, and 1.14, respectively, and labels the confidence interval percentage as 10, but does not provide lower limits. Those are incomplete intervals as posted, so their full width and relation to the null value cannot be evaluated from the record.

Precision is distinct from clinical importance. Even a precisely estimated difference would need interpretation in the context of the endpoint and other outcomes; a less precise estimate leaves more uncertainty about the magnitude and direction. The registry record does not report enough information to resolve that uncertainty beyond the posted results.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect in each comparison, not the trial’s original design calculation. For these binary outcomes, the figures are participants per arm. The planning assumptions are a two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation; the assumed effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the selected effect if that effect were the true one. The 90% power column gives the corresponding planning number for a 90% chance. These are conditional design calculations, not evidence about the probability that the trial’s observed result is true, and they are not observed power.

Rows that plan for 75% or 50% of the observed effect represent smaller effects than the row based on 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. The planning figures differ across comparisons because they use the corresponding observed effect as their starting point. They should not be read as a revised enrollment target validated by the original investigators.

The sample-size curve is a visual way to relate assumed effect size to required sample size under the planning setup. It helps show the general increase in required participants as the target effect becomes smaller. It does not add information about what the sponsor planned, whether the trial achieved a chosen power, or how missing data and multiple comparisons might alter a future design.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.233; treatment proportion p₁ = 0.193; average p̄ = 0.213.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5792 = 1.1352.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5785 = 0.4869.
4. n = (1.1352 + 0.4869)² / (-0.0404)² = 1,615.9, rounded up to 1,616 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.233333333333333                          # control proportion
p1 <- 0.192982456140351                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1619423)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,616 (80% power), 2,163 (90% power)
 75% of observed effect: n per arm = 2,923 (80% power), 3,913 (90% power)
 50% of observed effect: n per arm = 6,687 (80% power), 8,951 (90% power)
power.prop.test: 1615.9 
Simulated power at n = 1,616 per arm: 0.810 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The sponsor’s reported primary analyses use the Cochran-Mantel-Haenszel method and report odds ratios. For placebo versus the 2 µmol/kg group, the reported odds ratio is 0.78 and the p-value is 0.31. For placebo versus the 5+10 µmol/kg group, the reported odds ratio is 0.55 and the p-value is 0.15. For placebo versus the 2+5+10 µmol/kg group, the reported odds ratio is 0.62 and the p-value is 0.16. Each analysis is labeled as a superiority comparison.

The recalculated estimates use unadjusted risk differences from the posted counts, so they answer the comparison using a different effect measure and a simpler calculation. Differences between those results and the sponsor’s odds-ratio results should not be treated as direct contradictions: the measures have different scales, and the analysis methods differ. The registry does not provide the stratification details needed to reproduce the sponsor’s Cochran-Mantel-Haenszel analyses.

The sponsor’s entries list a confidence interval percentage of 10 and an upper limit for each odds ratio, but omit the lower limit. That makes the posted interval information incomplete. The discrepancy indicator is false in the registry record, so no discrepancy between the sponsor analysis and the recalculation is flagged. The recalculation remains a supplementary unadjusted reading; the sponsor’s own analysis is the principal reported analysis, while its missing interval detail and unreported method specifics constrain independent assessment.

14. Multiplicity, Missing Data and Analysis Populations

Three PledOx-versus-placebo primary-outcome comparisons are posted: 2 µmol/kg, 5+10 µmol/kg, and 2+5+10 µmol/kg. When several hypotheses are tested, the chance of obtaining at least one result that appears unusual under a null model can increase. Methods for handling this issue may adjust the tests or define a hierarchy of comparisons. Whether the sponsor used a multiplicity adjustment, prespecified a hierarchy, or treated any comparison as primary over the others is not reported in the registry record.

The sponsor’s posted p-values are 0.31, 0.15, and 0.16. The recalculated p-values are unadjusted: 0.595, 0.072, and 0.176, in the same comparison order. These should not be interpreted as multiplicity-adjusted evidence. The planning illustrations use a two-sided significance level 0.05, but that sample-size assumption does not establish the inferential plan used for the trial’s reported analyses.

The registry identifies the primary-outcome population as the full analysis set. It does not define the set, report how many participants contributed to each analysis beyond the posted group counts, or describe exclusions. Missing-data handling is also not reported in the registry record. There is no basis in the posted information to say whether there were missing outcome measurements or, if so, how they were treated.

No secondary outcomes are posted in the registry results record. The listed outcome measure count is one, and the posted analyses number three, corresponding to the displayed comparisons. Those record details do not establish that no other outcomes were collected; they indicate that secondary outcome results are not reported in the registry record.

Further details of the statistical plan are not reported, including the sponsor’s criteria for analysis populations, the handling of participants who discontinued treatment, and the approach to combining information across randomized parts. These omissions limit the ability to evaluate whether the posted analyses followed a prespecified plan and to reproduce them independently.

15. 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: infection (9.1%), hypersensitivty (9.1%), ileus (9.1%), nausea (7.7%), constipation (7.7%).

The registry lists serious adverse events and other adverse events by group, with the number at risk and the number affected. In the placebo plus FOLFOX6 group from parts 2a and 2b, 6 of 60 participants had a serious adverse event, 49 of 60 had another adverse event, and 2 deaths are listed. In the 2 µmol/kg PledOx plus FOLFOX6 group from parts 2a and 2b, the corresponding counts are 7 of 57, 45 of 57, and 1 death.

For the 5 µmol/kg group in part 2b, 3 of 45 had a serious adverse event, 35 of 45 had another adverse event, and 1 death is listed. For the 10 µmol/kg group in part 2a, the entries are 2 of 11, 9 of 11, and 1 death. The separate part 1 dose-escalation group lists 2 of 13 with a serious adverse event, 10 of 13 with another adverse event, and 0 deaths. Part 1 was open dose escalation and should not be treated as one of the randomized primary-outcome comparisons.

The listed serious-event terms include Infection, Hypersensitivty, and Ileus at 9.1% each, and Nausea, Constipation, and Neutropenia at 7.7% each. These entries describe reported event terms and percentages; they do not establish comparative risk or causation. The adverse-event summaries are descriptive and should be considered separately from the primary neuropathy endpoint. The registry record does not provide enough detail to interpret these figures as adjusted safety comparisons.

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

The primary results show the counts of participants meeting a defined neuropathy threshold during cycles 1 to 8. The observed counts were 14 of 60 in placebo, 11 of 57 in the 2 µmol/kg group, 6 of 56 in the 5+10 µmol/kg group, and 17 of 113 in the combined 2+5+10 µmol/kg group. The unadjusted risk-difference estimates are negative for all three PledOx comparisons, meaning that the observed event proportions were lower than placebo in those calculations.

Those observations do not, on their own, establish that PledOx caused a reduction in neuropathy. The recalculated intervals all include zero, and the sponsor’s reported p-values are 0.31, 0.15, and 0.16. The sponsor’s analyses use odds ratios and a Cochran-Mantel-Haenszel method, while the recalculations use unadjusted risk differences. In addition, the reported sponsor intervals are incomplete in the registry record. Together these registry entries warrant a cautious reading of the estimates rather than a categorical conclusion.

The results do not answer whether PledOx affects cancer control, survival, other symptoms, or quality of life. No secondary outcome results are posted in the registry record. The primary outcome concerns a particular grade threshold for paraesthesia or dysaesthesia, assessed over a limited treatment period, rather than every possible manifestation of neuropathy or toxicity.

The record also does not report the original sample-size justification, analysis plan details, multiplicity approach, or missing-data handling. These gaps matter because they affect how the estimates and uncertainty should be interpreted. The findings are best understood as the posted primary-outcome counts and analyses, with meaningful uncertainty and limitations in the available reporting—not as a complete account of treatment benefit or harm.

17. Why This Trial Matters Statistically

This trial illustrates how a binary clinical endpoint can make a complex symptom outcome easier to compare while also narrowing what the result represents. Neuropathy grade 2 or higher is a clinically interpretable threshold, but it does not retain the full range of severity or symptom experience. Readers should distinguish the threshold event from broader claims about neurological toxicity.

It also demonstrates why effect measures need to be read on their own scales. An odds ratio from a Cochran-Mantel-Haenszel analysis and an unadjusted risk difference answer related but non-identical statistical questions. Placing the estimates side by side without acknowledging the method and scale could lead to mistaken interpretation. In this case, the registry does not report enough information to reconstruct the sponsor’s stratified analysis in full.

The multiple comparisons make reporting of the analysis plan important. Three PledOx groupings are compared with the same placebo group, but the registry does not state whether the analyses were adjusted for multiplicity or organized by a prespecified hierarchy. The unadjusted recalculations are useful descriptive checks, but they do not resolve that missing design information.

Finally, confidence intervals and complete reporting are central to interpreting a trial result. The recalculated intervals span zero, and the sponsor’s posted odds-ratio intervals lack lower limits. That combination highlights why a point estimate or p-value alone is not enough. The available data can describe the observed comparison, but the precision and analysis details constrain what can be concluded.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record describes a study conducted in multiple parts, including an open dose-escalation part with no planned outcomes and randomized parts 2a and 2b with different dose groups. The primary comparisons combine dose groups in ways that reflect those parts, but the record does not fully explain the analytic rationale or the handling of part-specific differences. This complicates interpretation of the pooled dose groupings.

The sponsor’s reported analyses are identified as Cochran-Mantel-Haenszel odds ratios, but the stratification factors and further model details are not reported in the registry record. Their interval entries provide upper limits and a confidence interval percentage of 10, but no lower limits. The completeness of the sponsor’s uncertainty reporting is therefore limited.

The registry identifies a full analysis set but does not define it. It also does not report the handling of missing outcome measurements, discontinuations, or analysis exclusions. The original sample-size justification and the trial’s own statistical analysis plan are not reported. Multiplicity handling for the three comparisons is likewise not reported.

The primary outcome covers neuropathy grade 2 or higher for specified symptoms during cycles 1 to 8; it does not describe symptom severity below the threshold or all adverse effects. No secondary outcome results are posted. Safety counts include the open dose-escalation group as well as randomized groups, so they are not a single uniform randomized comparison. These limitations concern what can be evaluated from the registry record and do not establish that a particular method or outcome was absent from the full study documentation.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer — NCT01619423.
• Registry record last updated 2018-07-06; status last verified 2018-07.
• Results first posted 2018-07-06.
• 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.

22. Record Summary

NCT01619423 is a completed randomized, triple-masked, parallel-group study listed in PHASE1 and PHASE2. It enrolled 186 participants with advanced metastatic, stage IV colorectal cancer. The study began in 2012-09 and reached primary completion in 2016-03.

The primary outcome was the number of participants with neuropathy grade 2 or higher for paraesthesia or dysaesthesia according to the Oxaliplatin Specific Sanofi Scale criteria, assessed every second week during cycle 1-8, for up to 16 weeks. The posted results compare placebo plus FOLFOX6 with PledOx groupings plus FOLFOX6. Sponsor analyses use Cochran-Mantel-Haenszel odds ratios; supplementary recalculations use unadjusted risk differences from the posted counts.

The registry does not report secondary outcome results, a complete sponsor confidence interval for the odds ratios, the trial’s original sample-size assumptions, multiplicity handling, or missing-data procedures. The available results describe the recorded primary endpoint and adverse-event counts but leave important details of analysis and interpretation unresolved.