Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma (NCT00131937), a na phase 2 study. The primary outcome is Overall Response (OR) Rate.

2. Clinical Question

This is a descriptive question about response observed among participants receiving sorafenib. It is not a randomized comparison of sorafenib with another treatment or with no treatment. Without a concurrent comparator, the response proportion alone cannot separate an effect associated with treatment from other explanations, such as the course of the disease or differences among participants.

The registry describes the primary outcome as a proportion and gives a response assessment schedule. It does not report the number of participants who responded, the resulting overall response rate, or the confidence interval bounds. Therefore, the registry record does not establish what response proportion was observed or how precisely it was estimated.

3. Trial Design

This is a phase II study sponsored by the National Cancer Institute (NCI), with a single-group model and no masking. The registry lists enrollment of 14 participants and describes one treatment group receiving sorafenib tosylate. Allocation is recorded as not applicable. There is no randomized control arm, so the study design supports description of outcomes within the treated group rather than a like-for-like treatment comparison.

The treatment schedule is oral sorafenib 400 mg twice daily on days 1–28, with courses repeating every 28 days when disease has not progressed and toxicity is not unacceptable. The registry identifies the study as completed. Its recorded start is 2005-10 and primary completion is 2011-09.

The listed disease conditions include multiple lymphoma types. The brief summary specifically describes recurrent diffuse large B-cell non-Hodgkin lymphoma, while the condition list is broader. The registry record does not report further details that would clarify how the listed diagnoses were represented among the enrolled participants.

The primary outcome is overall response rate. Secondary outcomes are progression-free survival and overall survival. Although the registry lists three outcome measures, it records zero analyses. Numerical results for these outcomes are not reported in the registry record. The record also does not report the study's detailed statistical analysis plan, sample-size justification, or interim analysis procedures.

As a single-group phase II study, the design can describe outcomes and safety observations in the enrolled group. It does not provide a concurrent estimate of what would have occurred in a comparator group. This distinction is essential when interpreting response or adverse-event summaries: they describe the participants in this study and do not by themselves quantify a comparative treatment effect.

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

Reasons for not completing this period:

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 Overall Response (OR) Rate, measured over Assessed at the end of Cycle 2 and Cycle 6 (1 cycle = 28 days). Then every 3 months beginning Cycle 9 if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years..

The primary endpoint is the overall response rate, expressed as a proportion of participants. Overall response combines complete response, complete response/uncertain, and partial response. The registry states that responses were assessed using criteria from the International Workshop to Standardize Criteria for NHL (Cheson, 1999). In broad terms, these criteria use changes in disease findings, including lymph node or mass size and, where relevant, findings in the spleen, liver, or bone marrow.

Response was assessed at the end of Cycle 2 and Cycle 6, with one cycle defined as 28 days. The planned schedule then calls for assessments every 3 months beginning Cycle 9 for participants less than 2 years from study entry, and every 6 months for those 2–3 years from study entry, up to 3 years.

A proportion is useful for describing how often a defined response category occurred in the study group. It is a binary outcome at the participant level: each participant is classified according to whether the response definition was met. The registry record does not report the observed number of responses, the overall response proportion, or the 90% confidence interval bounds. Thus, the endpoint definition and assessment schedule are available, but the numerical primary outcome is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either meets the overall response definition or does not. The registry describes the outcome as a proportion of participants. General: a proportion is calculated by counting participants with the specified event and relating that count to the relevant group size. The registry record does not report the response count or response proportion for this study, so no numerical response estimate can be interpreted from it.

What does a confidence interval describe?

The primary outcome specifies a 90% confidence interval. General: a confidence interval expresses uncertainty around an estimate under the method used to construct it. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. It is not a guarantee that the true value lies within the particular interval, and it does not measure the probability that treatment is effective. Here, the interval bounds are not reported in the registry record, so its width and the precision of the response estimate cannot be assessed.

What do the response criteria contribute?

The registry says response was assessed using criteria from the International Workshop to Standardize Criteria for NHL (Cheson, 1999). Overall response includes complete response, complete response/uncertain, and partial response. The criteria use specified findings such as disappearance or reduction of disease evidence, changes in dominant lymph nodes or masses, and assessment of other disease sites. Defining the outcome in advance helps make the classification more consistent than an informal judgment. However, a clear definition does not substitute for the missing numerical result, and the record does not provide participant-level response classifications.

How should the assessment schedule be understood?

Assessments are specified at the end of Cycle 2 and Cycle 6, with one cycle lasting 28 days. The registry then describes assessments every 3 months beginning Cycle 9 for participants less than 2 years from study entry and every 6 months for those 2–3 years from study entry, up to 3 years. This schedule explains when response assessments were intended to occur. The record does not report how many participants completed each assessment, whether any assessments were missed, or how incomplete follow-up was handled.

What does a single-group design permit?

The study model is single group, allocation is not applicable, and masking is none. General: a single-group design can describe outcomes among participants receiving the study treatment. Without a concurrent control group, it cannot directly estimate a treatment contrast. Changes in disease status over time may be observed, but their cause cannot be assigned to the treatment by comparison within this design alone. Lack of masking can also matter when outcomes involve assessment judgments, although the registry record does not report whether or how this was addressed.

How do planning illustrations differ from study results?

The planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe the effect to detect as a stated fraction of the observed effect. For time-to-event outcomes, the stated method uses the total number of events with the Schoenfeld approach; for other outcomes, the planning quantity is participants per arm. These are planning illustrations, not observed power and not evidence that the trial itself used a two-arm design. The actual study is single group. The registry record does not report the study's own sample-size justification or its statistical plan.

General: over-dispersion arises when the variability in count data exceeds what a simple model assumes. Accounting for it can affect uncertainty estimates and tests. The primary endpoint is described as a proportion rather than a count model, and the registry record does not report an over-dispersion analysis. No model, estimator, or test for the primary outcome is reported in the registry record, so a more specific account of the analysis method is not possible.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment (Sorafenib)")
n      <- c(14)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Sorafenib)  14  0  0.0  0.0  23.2  0.0  21.5  0.2  21.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: overall response, progression-free survival, and overall survival. The primary outcome is identified, but no analysis records are listed. The record does not report a multiplicity procedure, such as an adjustment across outcomes or a hierarchy for interpreting multiple tests. It is therefore not possible to determine whether the study's analyses accounted for the possibility of multiple statistical comparisons.

Missing data and analysis populations are also not described in sufficient detail. The registry record does not report how many participants had an evaluable primary outcome, how missing response assessments were treated, or whether participants were excluded from any analysis. It does not report a definition of an intention-to-treat, per-protocol, or other analysis population. Although enrollment is listed as 14, that number alone does not establish how many participants contributed to each outcome analysis.

The assessment schedule extends beyond the initial cycles, and the secondary outcomes are time-to-event measures. The registry record does not report censoring rules, follow-up completeness, handling of loss to follow-up, or the number of participants at risk at different assessment times. These details matter because incomplete observation can affect how outcome estimates are formed and interpreted.

These are reporting gaps in the registry record; they do not establish what procedures may have been used outside it. Without an analysis plan, analysis populations, and missing-data methods, readers cannot assess whether the posted outcome summaries, if available elsewhere, followed prespecified procedures.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fatigue (35.7%), rash maculo-papular (21.4%), platelet count decreased (14.3%), diarrhea (14.3%), white blood cell decreased (7.1%).

The registry lists one treatment group with 14 participants at risk for serious adverse events and 9 affected. For other adverse events, it lists 14 at risk and 14 affected. These figures describe the counts recorded in those categories for the study group. They are not a comparison between sorafenib and another treatment.

The serious adverse-event terms listed with percentages are fatigue, 35.7%; rash maculo-papular, 21.4%; platelet count decreased, 14.3%; diarrhea, 14.3%; white blood cell decreased, 7.1%; and neutrophil count decreased, 7.1%. These percentages should be read as descriptive entries in the registry's safety summary, not as comparative risk estimates.

General: adverse-event summaries depend on how events are defined, collected, and grouped, and on the period over which participants are observed. The registry record does not provide further detail on event severity grading, duration, attribution, or individual event counts for each listed term. It also does not report a control group. The figures therefore characterize recorded events in this group but do not establish a relative safety profile.

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

The study asks a clinically relevant descriptive question: what proportion of participants receiving sorafenib tosylate met the specified overall response criteria? The registry provides the treatment schedule, the response definition, and the planned assessment timing. It also records enrollment of 14 and gives selected adverse-event summaries.

The numerical response result is not reported in the registry record. Neither the overall response proportion nor its 90% confidence interval bounds are available. The registry also does not report numerical results for progression-free survival or overall survival. Consequently, the record does not support a conclusion about the observed response frequency, the precision of that estimate, or the secondary outcomes.

Even if a response proportion were available, the single-group design would remain important to its interpretation. A within-group response summary does not estimate how the same participants would have fared under another treatment. There is no randomized comparator and no concurrent control group in the registry record. The design therefore does not support a direct comparative treatment-effect estimate.

The adverse-event figures describe participants in the treatment group. They do not establish whether an event was more or less frequent than it would have been under another treatment, and the record does not report the additional details needed to characterize all aspects of safety.

In short, the record documents the study's question and design but does not report its main numerical outcome. The absence of a result in the registry record should not be interpreted as a zero response rate, as evidence of no effect, or as evidence that an outcome was not assessed. It means that the numerical outcome is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it separates a well-defined research question from the evidence needed to answer it. The record specifies a phase II, single-group study, an overall response endpoint, and a schedule for assessing response. Those design details identify what the study intended to describe, but the numerical response result is not reported in the registry record.

The endpoint is a proportion, and its interpretation depends on both the observed estimate and its uncertainty. The registry specifies a 90% confidence interval, yet neither the estimate nor the interval bounds are available. This makes the distinction between an outcome definition and an outcome finding especially important: knowing how response was defined does not reveal how often response occurred.

The design also illustrates the limits of within-group evidence. A single treatment group can provide a description of outcomes among enrolled participants, while a randomized comparison is needed to directly contrast outcomes between assigned groups. Since this study has no comparator group, its results would not by themselves establish a comparative treatment effect.

Finally, registry completeness affects statistical interpretation. The listed secondary outcomes, assessment schedule, and safety counts provide useful context, but absent analyses and missing-data details limit assessment of precision, follow-up, and analysis choices. Reading the record carefully means distinguishing what it reports—the design and definitions—from what it does not report—the primary numerical result, interval bounds, and secondary outcome estimates.

15. 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 lists a broad set of lymphoma conditions, while the brief summary emphasizes recurrent diffuse large B-cell non-Hodgkin lymphoma. It does not report the distribution of enrolled participants across the listed diagnoses or provide further detail about the study population. This limits assessment of how broadly any within-group observation would apply across the conditions named.

The study is single group, with allocation recorded as not applicable and masking recorded as none. There is no concurrent control group for interpreting outcomes comparatively. The registry record does not report further information about outcome assessment procedures that would clarify the role of unmasked assessment.

Enrollment is listed as 14, but the number contributing to each outcome is not reported. The primary response count and estimate are absent, as are the 90% confidence interval bounds. Results for progression-free survival and overall survival are also not reported in the registry record. The record does not provide missing-data methods, analysis-population definitions, censoring procedures, or a detailed statistical analysis plan.

The registry describes a treatment schedule and assessment timing, but does not report participant-level follow-up or completion of planned assessments. It also does not report the study's own sample-size justification or interim analysis procedures. These limitations prevent evaluation of the precision and robustness of the outcome analyses and do not establish which procedures may have been used outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma — NCT00131937.
• Registry record last updated 2015-09-03; status last verified 2015-07.
• Results first posted 2015-09-03.
• 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.

19. Record Summary

This completed phase II study, sponsored by the National Cancer Institute (NCI), evaluates sorafenib tosylate in a single group of participants with recurrent aggressive non-Hodgkin lymphoma. Enrollment is listed as 14. The treatment schedule is oral sorafenib 400 mg twice daily on days 1–28, with 28-day courses repeated in the absence of progression or unacceptable toxicity.

The primary outcome is overall response rate, assessed using the stated lymphoma criteria. Progression-free survival and overall survival are listed as secondary outcomes. The registry record does not report numerical results for these outcomes, including the primary response proportion and its 90% confidence interval. It lists selected adverse-event summaries but no comparator group. The record identifies the study design and outcome definitions, while leaving key efficacy estimates and statistical-analysis details unreported.