Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma (NCT01177397), a na phase 1, phase 2 study. The primary outcome is Part A: Number of Participants With Dose-limiting Toxicities.

2. Clinical Question

The broader study aim was to assess safety, tolerability, pharmacokinetics, and preliminary efficacy, and to identify a dose and tumor type for later-stage research. This is a dose-finding and early clinical evaluation, not a trial designed to compare CC-223 with an established therapy. Part B included disease-specific cohorts, and the listed secondary outcomes include changes in phosphorylated proteins in blood cells and tumor tissue. The registry record does not report a primary efficacy result or a between-treatment effect estimate.

3. Trial Design

This was a Phase 1/2, multicenter, open-label study of oral CC-223. The record lists the study as completed and gives enrollment as 226. Its start date is 2010-07-20 and its primary completion date is 2016-11-15. The study included people with advanced solid tumors, non-Hodgkin lymphoma, or multiple myeloma; the registry also names specific disease cohorts, including non-small cell lung cancer, glioblastoma multiforme, hepatocellular carcinoma, neuroendocrine tumors of non-pancreatic origin, diffuse large B-cell lymphoma, multiple myeloma, and hormone receptor-positive breast cancer.

The design is listed as single-group, with no allocation and no masking. All participants received CC-223. In Part A, serial groups received different dose levels, and the number of groups was to depend on the number of dose levels required to establish dose-limiting toxicity. The registry lists dose groups of 7.5 mg, 15 mg, 30 mg, 45 mg, and 60 mg for Part A. The specific dose-escalation rules, the criteria for selecting a dose for Part B, and any rules for moving between cohorts are not reported in the registry record.

Part A focused on dose finding and the number of participants with dose-limiting toxicities. Part B comprised disease-specific cohorts and included secondary outcomes based on changes in phosphorylated proteins. The record lists 24 outcome measures, but does not provide outcome-analysis entries. It also does not report a formal statistical analysis plan, randomization procedure, masking procedure beyond the open-label designation, or a sample-size justification. As there is no concurrent control group, differences between dose groups or tumor cohorts cannot be interpreted as randomized treatment effects.

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.

Only the first 6 of 12 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated participants in Part A.

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: All treated participants

Only the first 6 of 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part A: Number of Participants With Dose-limiting Toxicities, measured over From first dose up to 30 days after first dose.

The primary endpoint is the number of treated participants in Part A with a dose-limiting toxicity from the first dose through 30 days after the first dose. It is a participant count: each participant either met the endpoint definition during that window or did not. The registry record does not report the observed count.

The definition combines several kinds of clinically relevant events. It includes specified severe adverse events or laboratory abnormalities suspected to be related to CC-223, with stated exceptions, as well as selected prolonged glucose abnormalities, hematologic toxicities, liver-function test abnormalities, and adverse events that required a dose reduction during cycle 1. The record also describes particular duration thresholds and exclusions, so the endpoint is narrower than a count of every adverse event.

General statistical context: Dose-limiting toxicity is used in early dose-finding research to help characterize tolerability at different dose levels and inform later study decisions. The endpoint’s short, defined observation window supports a focused assessment after treatment begins; it does not capture all possible later harms. A count alone is also difficult to interpret without the number of participants assessed at each dose, the timing and completeness of follow-up, and a clear accounting of how events were attributed and classified. Those endpoint results and details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: A clinical endpoint is the outcome used to answer a study question. Here the primary endpoint is a count of participants meeting a defined dose-limiting-toxicity criterion during a specified period. The definition matters: it determines which events qualify, how events are attributed, and the period during which they are counted. In this study, the definition includes specified clinically relevant events and laboratory abnormalities, as well as certain prolonged toxicities and dose reductions. It also excludes some named events or circumstances. The registry record gives the definition, but not the observed endpoint count.

General statistical context: A participant count is often accompanied by a denominator, such as the number assessed at a dose. The count conveys how many participants met the endpoint; the denominator indicates how many were at risk of being counted. Counts can be unstable when groups are small, so a count from a small group should not be treated as a precise estimate of the underlying event frequency. Part A group sizes in the safety information range from 1 to 9 participants at the listed dose levels. These safety counts do not fill in the missing primary-endpoint result: the endpoint’s own count and analysis are not reported in the registry record.

General statistical context: A confidence interval expresses the range of values compatible with observed data under a statistical model, and communicates estimation uncertainty. An interval around a proportion or event rate can be especially wide with few observations. No confidence interval for the primary endpoint or for the posted adverse-event counts is reported in the registry record. Without an interval, readers cannot assess the precision of an estimated endpoint rate from the record. Even an interval would not correct limitations caused by the single-group design or establish that an event was caused by treatment.

General statistical context: Over-dispersion occurs when count variation is greater than a simple statistical model expects. It can make standard errors too small if the model assumes less variation than the data contain. This trial’s primary measure is a participant count rather than a reported model-based event rate, and no dispersion estimate or count-model analysis is reported in the registry record. Over-dispersion therefore cannot be evaluated from the posted primary endpoint information.

General statistical context: Randomization supports comparisons by making treatment assignment independent of participant characteristics on average. This study is listed as having no allocation and a single-group model, so its dose groups and disease cohorts are not randomized comparisons. Participants in different cohorts may differ in diagnosis and other ways, and the Part A groups were organized for dose finding. Comparing their raw counts cannot isolate the effect of dose or distinguish treatment effects from differences in participant mix, follow-up, or disease course.

General statistical context: Open-label means treatment assignment is not masked. In an early dose-finding study, that can affect how participants and investigators report, observe, or classify events. The endpoint’s criteria provide structure, but the registry record does not report blinded adjudication or other procedures intended to limit assessment bias. It also does not report an analysis plan describing how event attribution or missing assessments were handled.

General statistical context: Statistical significance and clinical importance are different questions. A p-value, when reported, assesses compatibility with a specified null model; it does not itself quantify the size or importance of an effect. The record lists no outcome-analysis entries and reports no p-values for the primary endpoint. Because there is no concurrent comparator and no posted primary endpoint estimate, a significance test cannot support a comparative conclusion.

The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. Those are planning assumptions for hypothetical comparisons, not the design of this single-group study. The record does not report a trial sample-size justification or an observed effect for the primary endpoint. Any planning sample sizes should therefore be understood as illustrations, not as observed power or as evidence that the study was powered to detect a particular result.

What can the reported counts establish?

The counts establish how many serious adverse events and deaths are listed for each group in the registry record. They do not establish whether events were caused by CC-223, whether participants had multiple events, or whether the groups differ because of dose or cohort. No comparative effect estimates or uncertainty intervals are reported.

What remains unknown?

The primary endpoint count, its analysis, the handling of missing data, the planned analysis population beyond the stated Part A treated participants, and any interim analyses are not reported in the registry record. The registry also does not report a protocol-level rationale for the chosen group sizes or the detailed methods used to assess pharmacokinetic or preliminary efficacy outcomes.

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("Part A: CC-223 7.5 mg", "Part A: CC-223 15 mg", "Part A: CC-223 30 mg", "Part A: CC-223 45 mg", "Part A: CC-223 60 mg")
n      <- c(1, 2, 9, 9, 7)
events <- c(0, 0, 1, 1, 2)
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  Part A: CC-223 7.5 mg  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Part A: CC-223 15 mg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Part A: CC-223 30 mg  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5
ARM  Part A: CC-223 45 mg  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5
ARM  Part A: CC-223 60 mg  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures, including the Part A dose-limiting-toxicity endpoint and secondary outcomes involving phosphorylated proteins in stimulated blood cells, monocytes, and tumor tissue. The record does not include outcome-analysis entries. It does not report a statistical plan describing which outcomes were confirmatory, how multiple outcomes or subgroup analyses were handled, or whether any adjustment for multiple testing was planned. Without that information, the intended interpretation of results across the many measures cannot be assessed.

The primary endpoint population is stated as all treated participants in Part A. The safety information is reported for Part A dose groups and Part B disease cohorts, but the registry does not explain whether those safety denominators represent all treated participants, all participants assessed, or another analysis population. The endpoint count itself is not reported. The record also does not describe exclusions from analysis, participant disposition by outcome, or how participants with incomplete observation were handled.

Missing data can affect an estimate when participants lack outcome assessments, particularly if the reasons for missingness are related to health status or treatment. General statistical context: Appropriate interpretation depends on knowing how much information is missing, why it is missing, and what assumptions an analysis makes about the unobserved outcomes. The registry record does not report missing-data counts or methods for the primary endpoint or secondary outcomes.

Interim analyses, stopping rules, and any statistical monitoring procedures are not reported in the registry record. The dose-finding description says the number of serial Part A groups would depend on the dose levels needed to establish dose-limiting toxicity, but it does not provide the operational rules governing dose decisions. These missing details limit assessment of how the study’s dose-finding process and outcome reporting were planned.

12. 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: general physical health deterioration (22.2%), peripheral motor neuropathy (15.4%), diarrhoea (14.3%), nausea (14.3%), vomiting (14.3%).

The safety information separates serious adverse events, other adverse events, and deaths by Part A dose group or Part B disease cohort. For each group, the serious-event count is accompanied by the number at risk; for example, the record lists 4 serious adverse events among 9 at risk in the Part A 30 mg group. The other-adverse-event counts are also listed by group. These are descriptive records, not randomized comparisons.

Across Part A, serious-event counts are listed as 0 of 1, 0 of 2, 4 of 9, 4 of 9, and 2 of 7 for the 7.5 mg, 15 mg, 30 mg, 45 mg, and 60 mg groups. Across Part B, they are 15 of 26 for non-small cell lung cancer, 6 of 13 for glioblastoma multiforme, 29 of 53 for hepatocellular carcinoma, 23 of 47 for neuroendocrine tumor, 17 of 28 for diffuse large B-cell lymphoma, 6 of 14 for multiple myeloma, and 11 of 17 for hormone receptor-positive breast cancer. The number of deaths is also given for each group, but the registry does not establish treatment attribution.

Small groups make raw counts especially sensitive to each participant’s outcome. Cohort comparisons are further limited because diagnoses and group sizes differ and there is no control group. A participant may have more than one adverse event; the record does not say that event counts represent distinct people for every listed term. The serious-event percentages listed for selected terms lack further denominator and attribution details. These data should be read as a registry safety description, not as estimates of comparative risk or proof of causation.

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

The study record documents an early clinical evaluation of oral CC-223 in a broad group of advanced cancers and blood cancers. It describes a dose-finding component and disease-specific cohorts, with safety, tolerability, pharmacokinetics, and preliminary efficacy among the study aims. The record provides group-level serious adverse-event counts, other adverse-event counts, death counts, and selected serious-event terms and percentages.

However, the primary endpoint result is not reported in the registry record. The number of Part A participants who met the dose-limiting-toxicity definition during the specified period is absent. No efficacy estimate, confidence interval, p-value, or comparative treatment effect is reported. The posted safety counts cannot replace these missing results or establish the benefit or harm attributable to CC-223.

The design also limits what can be inferred. There is no concurrent control group, allocation is listed as none, and the study is open-label. Differences in raw event counts across dose groups or tumor cohorts could reflect differences in group size, diagnosis, participant characteristics, observation, or event classification, as well as any treatment-related effects. The record does not provide an analysis that separates these possibilities.

General statistical context: An early-phase dose-finding study can describe observed events and support decisions about further research, but it ordinarily does not provide the same type of evidence as a controlled comparative trial. A result from a treated cohort does not by itself show what would have happened to the same participants under another treatment or no study treatment. The registry record also does not report the details needed to assess the precision of the primary endpoint or the handling of missing observations.

The defensible interpretation is therefore limited: the registry records that participants received CC-223 at the listed doses or in the listed cohorts and records adverse-event counts by group. The missing primary endpoint and efficacy analyses prevent a fuller assessment of the study’s stated aims. No conclusion about clinical benefit, comparative safety, or treatment causation follows from the record alone.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between a dose-finding question and a comparative-treatment question. Part A asked about dose-limiting toxicity after treatment began, while the overall study sought safety, tolerability, pharmacokinetic, and preliminary efficacy information. The single-group, open-label structure is suited to descriptive early evaluation, but it does not create randomized evidence that one dose or cohort had better outcomes than another.

The endpoint definition also shows why a count needs careful interpretation. Dose-limiting toxicity is not simply any adverse event: the registry specifies event types, severity, timing, exclusions, duration conditions, and dose-reduction criteria. A count based on such a definition depends on consistent event assessment and complete follow-up during the stated window. Although the definition is available, the endpoint count and its analysis are not reported in the registry record.

The posted safety summaries offer information about recorded events across dose groups and tumor cohorts, while also highlighting the limits of sparse descriptive data. Some groups are small, and the cohorts differ by diagnosis. Counts without an inferential analysis or uncertainty intervals do not show whether apparent differences are meaningful, precise, or attributable to treatment.

The record also lists many outcome measures, including pharmacodynamic measures of phosphorylated proteins. Multiple outcomes can provide a broad account of biological and clinical observations, but interpretation depends on a prespecified analysis strategy and clarity about which outcomes are primary or exploratory. The statistical plan and outcome-analysis entries are not reported in the registry record.

For researchers, the central lesson is that design, endpoint definition, analysis population, and reporting completeness jointly determine what can be inferred. A stated study aim is not itself a result. Without the primary endpoint count, outcome analyses, and supporting information on missing data and uncertainty, the registry supports a description of design and safety reporting, rather than a quantitative conclusion about efficacy or dose-related effects.

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.

Several limitations are specific to this study record. First, the primary endpoint is a Part A participant count, but that count is not reported. The registry provides the detailed dose-limiting-toxicity definition and observation period without reporting how many participants met it. This prevents direct assessment of the dose-finding result.

Second, the single-group, open-label design has no concurrent control. Part A dose groups were serial rather than randomized comparators, and Part B groups were organized by tumor type. Raw counts cannot distinguish treatment effects from cohort differences, and open-label assessment may influence event reporting or classification. The record does not report blinded event adjudication or specific safeguards against assessment bias.

Third, the safety groups vary in size, and some Part A groups contain few participants. Event counts from small groups are imprecise as descriptions of underlying risk. The registry does not report confidence intervals for the endpoint or safety outcomes, nor does it give enough information to assess follow-up completeness by group. Death counts are listed, but treatment attribution is not established.

Fourth, the record lists many outcome measures but contains no outcome-analysis entries. It does not report the statistical analysis plan, multiplicity strategy, interim analyses, stopping rules, missing-data methods, or detailed analysis populations. The dose-finding description does not give the operational decision rules for selecting or advancing doses. These omissions make it difficult to evaluate whether the posted summaries represent prespecified analyses or how participants with incomplete data were handled.

Finally, the registry states broad aims that include preliminary efficacy, but does not report efficacy estimates or comparative results. The record alone therefore cannot establish efficacy, comparative safety, or a treatment-caused explanation for the observed adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma — NCT01177397.
• Registry record last updated 2022-12-13; status last verified 2022-12.
• Results first posted 2022-11-15.
• 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 1/2, multicenter, open-label study evaluated oral CC-223 in people with advanced solid tumors, non-Hodgkin lymphoma, or multiple myeloma. The registry lists enrollment as 226, with a start date of 2010-07-20 and a primary completion date of 2016-11-15. The design is single-group, with no allocation or masking.

Part A used serial dose groups and focused on the number of treated participants with dose-limiting toxicity from first dose through 30 days after first dose. Part B included disease-specific cohorts and secondary outcomes involving phosphorylated proteins. The registry lists serious adverse events, other adverse events, and deaths by group.

The primary endpoint count, efficacy results, outcome analyses, confidence intervals, and detailed statistical plan are not reported in the registry record. The posted safety counts are descriptive and do not establish treatment causation or comparative effects.