Surgery and Oxaliplatin or Mitomycin C in Treating Patients With Tumors of the Appendix: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Surgery and Oxaliplatin or Mitomycin C in Treating Patients With Tumors of the Appendix (NCT01580410), a randomized phase 2 study. The primary outcome is The Difference in the Number of Grade 3 or 4 Hematologic Toxicities (Leukopenia, Thrombocytopenia, and Neutropenia) Between the Mitomycin C and Oxaliplatin Treatments.

2. Clinical Question

The clinical question is specifically about hematologic toxicity after surgery and HIPEC, not a general comparison of all possible benefits and harms of the drugs. A patient counted as an event if they had a qualifying grade 3 or 4 toxicity. The registry also lists disease-free survival, overall survival, and quality of life as secondary outcomes. Those measures address different aspects of follow-up and should be interpreted separately from the primary toxicity comparison.

3. Trial Design

This was a randomized, open-label, parallel-group phase II trial sponsored by Wake Forest University Health Sciences. The registry lists 136 participants as enrolled. Participants were assigned to surgical cytoreduction followed by HIPEC with mitomycin C or to surgical cytoreduction followed by HIPEC with oxaliplatin. The registry reports no masking, so treatment assignment was not concealed from participants and study personnel through blinding.

The trial is listed as completed. Its recorded start was 2009-05, and its primary completion was 2015-10. These dates describe the registry record and do not, by themselves, establish when every outcome was assessed or when every participant completed follow-up. The primary toxicity timeframe was within 4 weeks of surgery. The secondary survival outcomes were assessed up to 3 years, and quality of life was assessed throughout study completion, up to 3 years.

There are 61.0 participants in the posted primary-outcome summary for mitomycin C and 59.0 for oxaliplatin. These denominators do not add up to the listed enrollment of 136; the reasons for the difference are not reported in the registry record. The secondary-outcome summaries use 57.0 and 53.0 participants for each of the survival and quality-of-life measures. The record does not explain why those denominators differ from one another or from the primary-outcome denominators.

The registry names surgery and the two HIPEC drugs as interventions, and also lists a quality-of-life assessment. It does not report the detailed allocation procedure, site-level enrollment, eligibility criteria, or the original trial sample-size justification. Those details should not be inferred from the randomized phase II label or the observed enrollment.

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 The Difference in the Number of Grade 3 or 4 Hematologic Toxicities (Leukopenia, Thrombocytopenia, and Neutropenia) Between the Mitomycin C and Oxaliplatin Treatments, measured over Within 4 weeks of surgery.

The primary endpoint counts patients who experienced at least one grade 3 or 4 standard hematologic toxicity: leukopenia, thrombocytopenia, or neutropenia. The assessment timeframe was within 4 weeks of surgery. For this endpoint, the registry defines a patient with a qualifying toxicity as an event. The outcome is therefore a patient count, and its treatment comparison is based on the proportion of patients with an event in each arm rather than on how many separate toxicity episodes occurred.

Hematologic toxicities are relevant to a comparison of chemotherapy regimens because the treatments may have different safety profiles. A binary event measure makes it possible to compare the frequency of patients crossing the stated severity threshold in the two arms. It also focuses the primary comparison on serious-grade toxicities specified in the registry rather than every possible adverse effect. The registry describes the primary outcome as the observed rates in the two treatment arms and states that the planned comparison uses a two-sided chi-square test.

The endpoint has a defined event rule and a short assessment window, but the registry record does not report further details about how toxicity grading was assessed, how overlapping toxicities were handled, or how participants without an assessment in the timeframe were treated analytically. These omissions limit what can be concluded about the operational details of endpoint ascertainment.

7. Results Posted in the Registry

• Arm II (Oxaliplatin): 8.5% (5/59) versus 13.1% (8/61) on control; risk difference -4.6 percentage points (95% CI -15.7 to 6.4), risk ratio 0.65 (0.22–1.86); unadjusted two-proportion z-test p = 0.414.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The Difference in Percentage of Disease-free Survival Between the Two Treatment Arms up to 3 Years

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Arm II (Oxaliplatin): mean 59.40 versus 61.60 on control; difference -2.20 (95% CI -24.65 to 20.25), standardized effect d = -0.04; z-test p = 0.848.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm II (Oxaliplatin) and the control. The interval gives the range of effects that remain compatible with the data.

The Difference in Percentage of Overall Survival Between the Two Treatment Arms up to 3 Years

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Arm II (Oxaliplatin): mean 79.30 versus 75.70 on control; difference 3.60 (95% CI -13.20 to 20.40), standardized effect d = 0.08; z-test p = 0.674.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm II (Oxaliplatin) and the control. The interval gives the range of effects that remain compatible with the data.

Quality of Life as Assessed by Functional Assessment of Cancer Therapy: General (FACT-G)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Arm II (Oxaliplatin): mean 89.60 versus 85.50 on control; difference 4.10 (95% CI -0.48 to 8.68), standardized effect d = 0.34; z-test p = 0.079.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm II (Oxaliplatin) and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover disease-free survival, overall survival, and FACT-G quality of life. Across these different measures, the oxaliplatin arm has a lower disease-free survival mean, and higher overall survival and quality-of-life means than the mitomycin C arm. The intervals around the mean differences include zero for each measure. The unadjusted p-values are 0.848 for disease-free survival, 0.674 for overall survival, and 0.079 for quality of life. Those results describe the posted arm summaries but do not establish that the arms are the same or that an observed direction is a reliable treatment effect.

These secondary outcomes relate to the primary result by broadening the description beyond early hematologic toxicity. They address disease control, survival, and patient-reported quality of life over longer assessment periods. They are not substitutes for the primary endpoint: a difference in a survival rate or quality-of-life score would answer a different question from whether patients experienced grade 3 or 4 hematologic toxicity within 4 weeks after surgery.

The registry lists no reported analyses for the secondary outcomes. The posted comparisons are unadjusted recalculations from the arm summaries, and the record does not document a multiplicity strategy. When several outcomes are examined, the chance of finding a seemingly notable result by chance can increase. Without a prespecified hierarchy or adjustment plan in the record, isolated secondary p-values carry less weight than a primary analysis specified for the main trial question. Their interpretation should also account for the differing sample sizes and standard errors across outcomes.

The results are best treated as descriptive and exploratory evidence about the measured outcomes in the recorded participants. They offer context for the primary toxicity comparison, but the registry record does not support ranking the treatments overall or combining these distinct outcomes into a single judgment. The secondary estimates should be considered with their intervals and the limitations in reporting, rather than interpreted as definitive evidence of benefit or harm.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• The Difference in Percentage of Disease-free Survival Between the Two Treatment Arms up to 3 Years
• The Difference in Percentage of Overall Survival Between the Two Treatment Arms up to 3 Years
• Quality of Life as Assessed by Functional Assessment of Cancer Therapy: General (FACT-G)

9. Statistical Interpretation

10. Statistical Methods Explained

How is the primary outcome represented?

The primary endpoint is binary at the patient level: a patient either met the event definition or did not. The event is any grade 3 or 4 leukopenia, thrombocytopenia, or neutropenia within 4 weeks of surgery. The posted summaries report 8.0 events among 61.0 patients assigned to mitomycin C and 5.0 among 59.0 assigned to oxaliplatin. A risk or event rate expresses the share of participants meeting that definition in an arm. The risk difference subtracts the comparator-arm risk from the oxaliplatin-arm risk, so a negative estimate means the observed event risk is lower in the oxaliplatin arm.

What does a risk difference communicate?

A risk difference is an absolute-scale comparison. It describes the difference in event probability between treatment arms, rather than the relative change between them. The estimate of -0.046 is a difference on the risk scale; the interval from -0.157 to 0.064 describes a range of values compatible with the posted comparison under the interval method. Because that interval spans zero, the data are compatible with no difference as well as with a difference in either direction. It is important not to interpret the point estimate alone as a precise estimate of the underlying treatment contrast.

Why is a chi-square test named?

The registry description says the observed rates were to be analyzed using a two-sided chi-square test. In general, a chi-square test compares observed counts across categories with counts expected under a null hypothesis of no association or no difference. Here the categories are the two treatment arms and whether a patient did or did not meet the event definition. A two-sided test considers departures in either direction. The registry does not report a sponsor-conducted test result or a detailed statistical analysis report. The displayed p-value is an unadjusted calculation from the posted arm summaries, rather than a reported sponsor analysis.

How should the p-value be read?

The p-value of 0.414 describes the compatibility of the observed counts with the null hypothesis, assuming the test framework applies. It is not a measure of the probability that the null hypothesis is true, and it does not establish equivalence. A small p-value can indicate that observed data are unusual under a null model, while a larger p-value can arise when the data provide limited evidence against that model. Neither result, by itself, describes the range of plausible effect sizes; that is why the estimate and its interval need to be considered together.

What do the secondary comparisons represent?

The secondary outcomes include disease-free survival rate, overall survival rate, and Functional Assessment of Cancer Therapy: General (FACT-G) quality-of-life scores. The registry posts arm means and standard errors for these measures, followed by unadjusted mean differences and intervals. A mean difference places the arm contrast on the outcome's original scale. The reported standard error describes uncertainty around an estimated arm mean; it is not the same quantity as the standard deviation of individual observations. No sponsor-reported analyses are listed for these outcomes, so the posted comparisons should be understood as unadjusted calculations from the arm summaries rather than as evidence of a fully documented model-based analysis.

What can the methods record establish?

The randomized parallel design supports a planned comparison of the assigned strategies, but a complete assessment requires details about randomization implementation, analysis populations, missing observations, and outcome ascertainment. Those details are not reported in the registry record. The registry states that the primary outcome rates were to be compared by a two-sided chi-square test; it does not report a statistical plan explaining covariate adjustment, subgroup analyses, interim analyses, or multiplicity control. These points should remain unknown rather than being inferred from standard practice or from the trial phase.

For general statistical context, randomization aims to make the treatment groups comparable in expectation, while observed group composition can still differ by chance. An unadjusted comparison uses the posted arm summaries without accounting for additional covariates. A confidence interval conveys uncertainty in an estimate, whereas a p-value evaluates compatibility with a specified null model. Neither measure resolves limitations caused by incomplete reporting, small event counts, or unclear analysis populations. These are general distinctions, not additional details about the trial's undocumented analysis procedures.

11. Confidence Intervals and Precision

The primary risk-difference estimate for oxaliplatin relative to mitomycin C is -0.046, with an interval from -0.157 to 0.064. This interval is broad in relation to the point estimate and crosses zero. It allows for an event risk lower under oxaliplatin, little or no difference, or an event risk higher under oxaliplatin. The posted estimate therefore does not precisely identify the direction or magnitude of the primary contrast. The registry record does not state the confidence level associated with the interval, so no confidence level should be assumed from the record alone.

Precision is affected by the amount of information in the data, including the number of participants and the frequency of events. The primary summaries include 61.0 and 59.0 participants, with 8.0 and 5.0 events, respectively. With relatively few observed events, the estimate can remain uncertain even when the point estimate appears to favor one direction. A confidence interval is more informative than the point estimate alone because it displays a range of values compatible with the data and the method used to calculate it.

The uncertainty should not be mistaken for proof of equality or proof of a clinically important difference. The interval includes values on either side of zero, and the registry record does not define a threshold for a clinically important risk difference. Thus, statistical precision and clinical importance cannot be fully connected using the information recorded. The unadjusted p-value of 0.414 also does not narrow the range of plausible effects; it addresses a related but different question about compatibility with the null hypothesis.

For the secondary comparisons, intervals are also posted, but these are unadjusted and the registry lists no reported analyses. Their interpretation depends on the outcome scale and the analytic assumptions behind each calculation. The available summaries support cautious reading of the estimates, not claims of precise differences or equivalence.

12. 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 planning figures are illustrations based on the observed effects, not the trial's original design assumptions. For the primary binary outcome and the other non-time-to-event outcomes, the figures are participants per arm. The assumptions listed are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. Time-to-event planning figures, if present, would instead be total events using the Schoenfeld method; the posted secondary outcomes do not include a time-to-event planning table of that type.

The 80% power column gives the number of participants per arm in the planning calculation for an 80% chance of detecting the chosen effect under those assumptions, if that effect were the true one and the model assumptions held. The 90% power column uses a higher target chance of detecting that same chosen effect, which generally requires more participants. These are planning concepts, not guarantees about what a future study would find.

The rows use 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect as the effect sizes to detect. A smaller effect is harder to distinguish from random variation, so the planning calculation calls for more participants per arm as the target effect gets smaller. These figures are not observed power. They do not show the probability that the completed trial detected an effect, and they should not be read as a retrospective verdict on trial quality. The original sample-size justification and assumptions used by the trial team are not reported in the registry record.

13. 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 = 0.131; treatment proportion p₁ = 0.085; average p̄ = 0.108.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4388 = 0.8601.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4376 = 0.3683.
4. n = (0.8601 + 0.3683)² / (-0.0464)² = 700.9, rounded up to 701 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 <- 0.131147540983607                          # control proportion
p1 <- 0.0847457627118644                          # 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(1580410)
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 = 701 (80% power), 938 (90% power)
 75% of observed effect: n per arm = 1,306 (80% power), 1,748 (90% power)
 50% of observed effect: n per arm = 3,069 (80% power), 4,108 (90% power)
power.prop.test: 700.9 
Simulated power at n = 701 per arm: 0.797 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary hematologic toxicity outcome and three secondary outcomes: disease-free survival, overall survival, and quality of life. It does not report a multiplicity adjustment, a testing hierarchy, or a plan that specifies how conclusions across outcomes would be controlled. In general, testing several outcomes creates more opportunities for chance findings than focusing on a single prespecified comparison. Without a documented strategy, unadjusted secondary p-values should be treated as exploratory and should not be given the same evidential weight as a clearly specified primary test.

The record gives no sponsor-reported analyses for the secondary outcomes, and it does not provide a reported analysis result for the primary endpoint beyond the registered outcome description and posted arm summaries. The reported comparison calculations are unadjusted. Details of the original statistical analysis plan, including any planned covariate adjustment, subgroup analyses, interim analyses, or stopping rules, are not reported in the registry record. No inference about whether these procedures were or were not conducted is warranted.

Missing-data handling is also not reported in the registry record. The listed enrollment is 136, while the primary outcome summaries include 61.0 and 59.0 participants. Secondary outcome summaries include 57.0 and 53.0 participants. These differences may reflect distinct analysis populations or unavailable outcome observations, but the record does not explain the reasons. It does not state whether participants with missing data were excluded, imputed, censored, or handled using another method. Those possibilities should not be guessed.

The analysis population is not named in sufficient detail to determine whether results are intention-to-treat, per-protocol, or based on another defined group. The registry also does not state how adherence to assigned treatment, treatment crossover, or protocol deviations were handled. Such information matters because a randomized assignment comparison and a comparison restricted to participants who received or completed treatment answer different questions. In the absence of these details, interpretation should remain tied to the posted denominators and outcomes, with the population and missing-data limitations clearly recognized.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: low hemoglobin (60.3%), lymphopenia (41.0%), hypoalbuminemia (31.1%), serum glutamic oxaloacetic transaminase (27.6%), dyspnea (23.0%).

The registry reports serious adverse event figures for both arms. In the mitomycin C arm, 51 of 58 participants in the serious-adverse-event group are listed as affected; in the oxaliplatin arm, 54 of 61 are listed as affected. For other adverse events, the record lists 58 of 58 participants in the mitomycin C arm and 61 of 61 in the oxaliplatin arm as affected. One death is listed in each arm. These figures are descriptive counts, not adjusted comparisons of treatment-related risk.

The registry also lists serious adverse event terms and percentages: Low Hemoglobin at 60.3%, Lymphopenia at 41.0%, hypoalbuminemia at 31.1%, serum glutamic oxaloacetic transaminase at 27.6%, Dyspnea at 23.0%, and hypophosphatemia at 23.0%. The record does not make clear in this summary how these term-specific percentages are distributed by treatment arm or how their denominators were defined. They should not be used to construct an arm-to-arm comparison.

Serious adverse event reporting is not identical to the primary endpoint, which counts specified grade 3 or 4 hematologic toxicities within 4 weeks of surgery. The safety figures may use different definitions and assessment periods. The registry does not provide enough detail to attribute each adverse event or death to study treatment, to compare severity patterns fully, or to determine how events were collected.

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

The posted primary data show that qualifying grade 3 or 4 hematologic toxicities occurred in both treatment arms. The unadjusted comparison estimates a risk difference of -0.046 for oxaliplatin relative to mitomycin C, with an interval from -0.157 to 0.064 and an unadjusted p-value of 0.414. The estimate points toward fewer events in the oxaliplatin arm, but the interval includes zero and also allows a higher event risk in that arm. The evidence is not precise enough to establish the direction or size of a difference.

This result does not establish that the regimens are equivalent. Equivalence requires a defined margin and an analysis designed to assess whether the difference lies within that margin; neither is reported in the registry record. Nor does the result demonstrate that one regimen is superior. A non-small p-value is not proof that no effect exists, and a point estimate in one direction is not proof that a real treatment difference exists.

The secondary outcomes add information about disease-free survival, overall survival, and quality of life, but their unadjusted nature and the absence of reported sponsor analyses limit their evidential weight. Their measures and timeframes differ from the primary outcome. They cannot be combined into an overall comparison without further analytic details. The adverse-event summaries also describe a broader safety picture, but do not identify causal attribution or provide a complete comparative safety analysis.

Interpretation is further limited by the difference between the listed enrollment and the numbers in the outcome summaries, as well as the absence of reported information about analysis populations and missing data. The registry record does not state the original sample-size justification, the confidence level for the primary interval, or the detailed statistical analysis plan. Consequently, the most defensible reading is a description of the posted counts and estimates, accompanied by substantial uncertainty and reporting limitations—not a clinical recommendation or a definitive overall judgment about either treatment.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison should be read through both its estimate and its uncertainty. The primary point estimate is on one side of zero, but the interval crosses zero and reaches in both directions. A reader who attends only to the point estimate could overstate the evidence; a reader who treats the p-value as proof of no difference could also overstate it. Considering the event counts, risk difference, interval, and p-value together gives a more balanced account of what the posted data can support.

The study also demonstrates the distinction between a primary endpoint and multiple secondary outcomes. Hematologic toxicity within 4 weeks of surgery is a defined, patient-level event, while survival and quality of life address different questions and assessment periods. When secondary outcomes are reported without a documented multiplicity plan or sponsor analyses, they can inform context but should not be treated as equally confirmatory evidence.

Planning illustrations based on observed effects are another useful teaching point. Their participant requirements vary with the target effect and desired power, but they do not reveal the study's original design rationale or the probability that this completed trial detected an effect. The registry's original sample-size justification is not reported. Distinguishing prospective planning assumptions from retrospective outcome summaries prevents those figures from being misread as evidence about the trial's actual power.

Finally, the mismatch between enrollment and outcome denominators highlights the importance of transparent reporting about analysis populations and missing observations. Randomization is central to trial design, but readers also need to know who contributed to each analysis and how unavailable data were treated. These reporting details are necessary for a complete statistical interpretation, even when the treatment comparison itself can be calculated from the posted summaries.

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.

Several trial-specific limitations constrain interpretation. The registry lists 136 enrolled participants, but the primary outcome summaries contain 61.0 participants in the mitomycin C arm and 59.0 in the oxaliplatin arm. The registry record does not explain why these totals differ or whether the outcome denominators represent all randomized participants, participants who received treatment, or another analysis population. The secondary outcomes use still smaller arm summaries of 57.0 and 53.0 participants, with no explanation of missing observations or differences in follow-up availability.

The primary event counts are limited, and the interval for the risk difference is wide enough to include values in either direction. This limits precision in estimating the comparative event risk. The registry describes a two-sided chi-square test but does not report a sponsor analysis result, detailed analysis plan, or confidence level for the interval. It also does not state how endpoint grading was assessed, how multiple qualifying toxicities in a patient were treated, or how missing primary outcome data were handled.

The trial is open-label, with no masking reported. This describes the design but does not establish whether assessment was influenced by knowledge of treatment assignment. The registry does not report procedures for blinded outcome assessment or other safeguards. The recorded outcomes also have different timeframes: the primary toxicity endpoint is within 4 weeks of surgery, whereas the survival outcomes extend up to 3 years and quality of life is assessed throughout study completion, up to 3 years. Differences in duration and available participants complicate direct comparisons across endpoints.

Additional limitations include no reported multiplicity strategy for the secondary outcomes, no sponsor-reported secondary analyses, and no reported original sample-size justification. The registry does not provide enough information to assess protocol deviations, adherence, treatment crossover, or the detailed randomization process. These are limits of the available registry record; they should not be converted into assumptions about what the trial team did.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Surgery and Oxaliplatin or Mitomycin C in Treating Patients With Tumors of the Appendix — NCT01580410.
• Registry record last updated 2018-07-03; status last verified 2018-06.
• Results first posted 2018-03-21.
• 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

NCT01580410 is a completed, randomized, open-label, parallel-group phase II trial sponsored by Wake Forest University Health Sciences. It compared surgical cytoreduction followed by HIPEC with mitomycin C against surgical cytoreduction followed by HIPEC with oxaliplatin in patients with appendiceal tumors. The primary outcome was the number of patients with grade 3 or 4 leukopenia, thrombocytopenia, or neutropenia within 4 weeks of surgery.

The posted primary summaries list 8.0 of 61.0 participants with an event in the mitomycin C arm and 5.0 of 59.0 in the oxaliplatin arm. The unadjusted risk difference is -0.046, with an interval from -0.157 to 0.064 and p = 0.414. The interval includes zero and leaves uncertainty about the direction and size of the difference. Secondary outcomes include disease-free survival, overall survival, and FACT-G quality of life. The record does not report sponsor analyses for those outcomes, and important details about analysis populations, missing data, multiplicity, and the original sample-size justification are not reported in the registry record.