This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors (NCT01525602), a non-randomized phase 1 study. The primary outcome is Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01525602 |
| Phase | Phase 1 |
| Condition | Solid Tumors |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 74 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Daiichi Sankyo |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced solid tumors entered a three-part study. The registry describes Part 3 as an extension cohort for participants with advanced, metastatic, or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. The primary safety endpoint applies to the Safety Population in Parts 1 and 2.
Intervention
The study explored PLX3397 given with weekly paclitaxel. Parts 1 and 2 focused on escalating PLX3397 doses and confirming a recommended Phase 2 dose in combination with paclitaxel. Part 3 was intended to assess PLX3397 600 mg twice daily with weekly paclitaxel in the specified cancers.
Comparator
The registry describes a non-randomized, open-label, single-group study, not a randomized comparison. The record also lists Part 3 adverse-event groups for PLX3397, paclitaxel, and their combination. It does not describe these as randomized control groups, so they should not be treated as like-for-like comparative arms.
Primary question
The primary safety question was which treatment-emergent adverse events classified by preferred term were reported by more than 10% of participants in Parts 1 and 2 while receiving PLX3397 with paclitaxel. The endpoint is a descriptive safety measure. The registry record does not report the preferred-term results for this endpoint, so the frequency of those events cannot be assessed from the primary results description.
These aims combine dose exploration and safety description with later efficacy objectives. The stated purpose of Part 1 was to explore safety and tolerability across escalating PLX3397 doses with weekly paclitaxel and establish a recommended Phase 2 dose. Part 2 was intended to confirm that dose in participants with advanced non-resectable solid tumors. Part 3 addressed a more specifically defined group of cancers and included duration of response and progression-free survival among its secondary outcomes.
Because the study was non-randomized and open-label, it does not establish a randomized treatment contrast. Its registry description supports questions about which adverse events were recorded and how the study was structured, but not a causal comparison between treatments. The primary endpoint concerns reported event types and frequency in Parts 1 and 2; it is distinct from the secondary efficacy outcomes and from the serious adverse-event counts listed separately.
3. Trial Design
This was a completed phase 1b study with a non-randomized allocation, no masking, and a single-group model in the registry record. It enrolled 74 participants. The study started in 2012-05, and primary completion was recorded as 2017-12. The sponsor was Daiichi Sankyo. The registry lists solid tumors as the condition.
The study had three parts. Part 1 used sequential PLX3397 dose escalation in combination with paclitaxel in participants with advanced solid tumors. Part 2 was an extension cohort at the recommended Phase 2 dose in advanced solid tumors. Part 3 was an extension cohort at that dose for participants with advanced, metastatic, or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. The registry describes these cohorts as closed to recruitment.
The brief description states that the study was designed to explore safety and tolerability, establish a recommended Phase 2 dose, confirm that dose, and determine efficacy for PLX3397 600 mg twice daily combined with weekly paclitaxel in the specified Part 3 cancers. These are stated aims, not evidence that any particular dose was confirmed or that an efficacy outcome was achieved.
The record lists treatment groups for adverse-event reporting, including dose cohorts in Part 1, a Part 1 and 2 cohort, and separate Part 3 listings for PLX3397, paclitaxel, and the combination. Those listings do not override the overall non-randomized, single-group design or establish a randomized contrast. The registry record does not report the allocation procedures for those listed Part 3 groups.
Duration of response is listed as a secondary outcome for Parts 1 and 2 and separately for Part 3. Progression-free survival is listed for Part 3. Additional secondary outcomes concern pharmacokinetic measures and treatment-related adverse events. The record does not report results for these outcomes in the information available for this analysis.
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: An open-label study. In Part 1 (dose escalation), participants were sequentially enrolled and received doses of PLX3397 600 to 1600 mg/day. In Part 2 (dose expansion), PLX3397 was administered at the recommended phase 2 dose with paclitaxel. In Part 3, PLX3397 was administered at 600 mg twice daily with paclitaxel; 2 participants were not dosed.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Part 1: Cohort 1; 600 mg/Day | Part 1: Cohort 2; 800 mg/Day | Part 1: Cohort 3; 1000 mg/Day | Part 1: Cohort 4; 1200 mg/Day | Part 1 and 2: Cohort 5; 1600 mg/Day | Part 3: PLX3397 600 mg BID |
|---|---|---|---|---|---|---|
| STARTED | 9 | 3 | 3 | 6 | 33 | 7 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 9 | 3 | 3 | 6 | 33 | 7 |
Reasons for not completing this period:
| Reason | Part 1: Cohort 1; 600 mg/Day | Part 1: Cohort 2; 800 mg/Day | Part 1: Cohort 3; 1000 mg/Day | Part 1: Cohort 4; 1200 mg/Day | Part 1 and 2: Cohort 5; 1600 mg/Day | Part 3: PLX3397 600 mg BID |
|---|---|---|---|---|---|---|
| Adverse Event | 1 | 0 | 1 | 1 | 3 | 3 |
| Disease progression | 6 | 3 | 2 | 5 | 22 | 2 |
| Clinical progression | 2 | 0 | 0 | 0 | 0 | 0 |
| Non-compliance | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 1 |
| Physician Decision | 0 | 0 | 0 | 0 | 3 | 0 |
| Death | 0 | 0 | 0 | 0 | 1 | 1 |
| Unqualified based on biopsy; not dosed | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety events were assessed in the Safety Population.
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: The baseline analysis population included all participants who were treated and included in the Safety Population (n=72).
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | Part 1: Cohort 1; 600 mg/Day | Part 1: Cohort 2; 800 mg/Day | Part 1: Cohort 3; 1000 mg/Day | Part 1: Cohort 4; 1200 mg/Day | Part 1 and 2: Cohort 5; 1600 mg/Day | Part 3: PLX3397 600 mg BID |
|---|---|---|---|---|---|---|---|
| Participants analysed | 9 | 3 | 3 | 6 | 33 | 7 | |
| Age, Continuous | years | 56.4 (SD 14.2) | 55.0 (SD 5.3) | 60.3 (SD 11.1) | 58.7 (SD 16.4) | 58.9 (SD 10.7) | 64.0 (SD 10.4) |
| Sex: Female, Male: Female | Participants | 6 | 3 | 1 | 3 | 20 | 7 |
| Sex: Female, Male: Male | Participants | 3 | 0 | 2 | 3 | 13 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 0 | 1 | 2 | 0 |
| Race (NIH/OMB): White | Participants | 9 | 2 | 3 | 5 | 29 | 7 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 9 | 3 | 3 | 6 | 33 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population), measured over From post first dose up to 28 days after the last dose, up to 5 years 9 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants in the Safety Population who experienced treatment-emergent adverse events classified by preferred term and reported by more than 10% of participants in Parts 1 and 2. The registry describes the observation period as beginning after the first dose and continuing up to 28 days after the last dose, up to 5 years 9 months.
A treatment-emergent adverse event is an event recorded during the defined treatment-emergent period; the endpoint description does not, by itself, establish that an event was caused by study treatment. Classification by preferred term groups reported events using standardized terms. The percentage measure describes how commonly each qualifying term was reported in the specified safety population.
General statistical context: adverse-event frequency is a descriptive way to characterize safety during a study. It can help identify which event types were reported often enough to meet a stated reporting threshold. It does not alone establish causality, severity, or comparative risk. The registry record does not report the primary endpoint’s preferred-term list or the corresponding percentages, so the measure’s actual results are not available in the record described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary safety endpoint, but does not report its results by preferred term. The endpoint description says that treatment-emergent adverse events reported by more than 10% of participants in Parts 1 and 2 are reported. Without the listed terms and their corresponding frequencies, the primary endpoint cannot be interpreted as a set of observed event rates. No confidence intervals or other precision measures for this endpoint are reported in the registry record.
Separate serious adverse-event data are recorded by group. For example, Part 1 Cohort 1, 600 mg/Day lists 1 serious adverse event among 9 at risk; Part 1 Cohort 3, 1000 mg/Day lists 3 among 3; and the Part 1 and 2 Cohort 5, 1600 mg/Day group lists 10 among 33. The Part 3 PLX3397 600 mg BID group lists 5 among 7, the paclitaxel 80 mg/m^2 group lists 2 among 5, and the combination group lists 3 among 6. These are descriptive counts in the registry’s safety data, not estimates from a randomized treatment comparison.
The registry also lists deaths for each group, but does not report the cause or relationship to treatment in this record. A death count should not be interpreted as a treatment-related death count unless that attribution is explicitly reported. The serious adverse-event terms listed as most frequent include Tooth infection, Abscess, Cellulitis, Device-related sepsis, Sudden cardiac death, and Febrile neutropenia, each reported as 33.3%. The record does not connect those term percentages to a particular group in the information.
General statistical context: event percentages and counts describe what was recorded in a particular study population and observation period. Their precision depends in part on the amount of information available; estimates based on small groups can be uncertain. Event definitions, follow-up, and which participants contribute to each analysis also matter. Those details should be considered alongside the numbers, and the registry record does not provide enough endpoint-level information to assess them fully for the primary outcome.
The study was non-randomized and open-label. Accordingly, differences among the listed groups would not be interpretable as unbiased treatment effects: the groups were not established as exchangeable through random assignment, and the registry does not give a like-for-like control comparison. The posted information supports a description of the study’s aims and recorded safety counts, but does not establish comparative benefit or harm.
9. Statistical Methods Explained
What does a percentage endpoint describe?
The primary outcome is expressed as a percentage of participants with qualifying treatment-emergent adverse events, classified by preferred term. General statistical context: a percentage communicates the proportion of an analysis population with a recorded event, while the underlying count and denominator show how much information contributes to that estimate. A percentage is not a measure of how severe an event was, and it does not show whether treatment caused it.
The endpoint is threshold-based: the description identifies terms reported by more than 10% of participants in Parts 1 and 2. Such a threshold can focus reporting on more frequently reported events, but events that do not meet it are not thereby shown to be absent. The record does not report the primary endpoint’s terms, counts, or percentages, so its observed pattern cannot be reconstructed from the endpoint definition alone.
Why does the study structure matter?
The design is non-randomized, open-label, and described overall as a single-group study. General statistical context: randomization can make treatment groups more comparable, on average, with respect to measured and unmeasured characteristics. Without random assignment, differences between groups may reflect who entered each group, their disease characteristics, dose, follow-up, or other factors, rather than the treatment itself. Open-label conduct also means the study was not masked, although the record does not specify how that affected any particular assessment.
The study combined dose escalation and extension cohorts across different parts and disease settings. Dose groups and the Part 3 listings should therefore be read in their stated context. They are not interchangeable observations from a randomized head-to-head comparison. The registry record does not report the detailed dose-escalation rules, the rationale for cohort sizes, or any adjustment procedure for comparisons across cohorts.
What can the serious-event counts tell us?
The adverse-event record gives the number at risk and the number affected for serious events in each listed group. These counts can describe the recorded burden within the listed group. They do not, by themselves, estimate a causal treatment effect or establish that an event was caused by treatment. General statistical context: the denominator is essential when interpreting a count, and small denominators can make an observed percentage change substantially with even a small change in the count.
The listed serious-event terms have percentages but are not tied to a specific group in the record described. The count of deaths is also reported by group, without a cause or treatment relationship in the record. It would therefore be inappropriate to infer that a listed death was caused by a particular drug, or to equate the serious-event term percentages with the primary endpoint’s preferred-term results.
What do planning calculations mean?
The registry record does not report the trial’s sample-size justification or power plan. The planning illustration associated with the posted results is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is the total number of events; for other outcomes, it is participants per arm.
General statistical context: a planning calculation asks how much information might be needed under specified assumptions. It is not evidence that the trial had a particular probability of detecting an effect, and it does not change what was observed. Planning based on an observed effect is illustrative rather than a substitute for a prespecified design rationale. The registry record does not report the sample-size justification used to plan this study, and no planning output values are reported in the record described.
How should uncertainty be considered?
General statistical context: a confidence interval describes a range of values compatible with the data under a statistical model and procedure. It conveys uncertainty in an estimate; it does not make an observational contrast causal. The registry record does not report confidence intervals for the primary endpoint in the information described. Without endpoint counts, denominators, and a stated analysis, the precision of the primary safety measure cannot be assessed.
Over-dispersion is a general issue for count data when variability exceeds what a simple model assumes. Accounting for it can affect uncertainty estimates in suitable analyses. The primary outcome is described as a percentage of participants, not as a count rate with a specified over-dispersion model. The registry record does not report a model or variance adjustment for this endpoint, so no such method should be assumed.
The record lists 13 outcome measures and 0 analyses. This does not provide the missing endpoint-level results or a complete account of the statistical analysis plan. The specific inferential methods, if any, used for the reported outcomes are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 13 outcome measures, including the primary treatment-emergent adverse-event endpoint and secondary outcomes for duration of response, progression-free survival, pharmacokinetics, and treatment-related adverse events. It lists 0 analyses. The record does not report a multiplicity adjustment, a testing hierarchy, or a plan for interpreting several outcomes together.
General statistical context: when many outcomes or event terms are examined, the chance of observing an unusual result by chance can increase if each is tested separately. A prespecified strategy can help define which results are confirmatory and how multiple tests are handled. The registry record does not report such a strategy, so no adjustment or hierarchy should be presumed.
Missing-data methods and outcome-specific analysis populations are not reported in the registry record. The primary endpoint identifies the Safety Population, while several secondary outcomes specify an Efficacy Evaluable Population. The record does not define the eligibility rules for these populations, how missing observations were handled, or whether participants with incomplete follow-up were included in each outcome analysis.
These omissions limit interpretation of the reported safety counts and make it impossible to assess whether the populations contributing to different outcomes were comparable. The event observation period is described for the primary endpoint, but the record does not provide details of participant-level follow-up, censoring, or missing event information for that endpoint. Such methods should not be inferred from the study’s aims or design description.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Part 1: Cohort 1; 600 mg/Day | 1 | 9 | 11.1% |
| Part 1: Cohort 2; 800 mg/Day | 1 | 3 | 33.3% |
| Part 1: Cohort 3; 1000 mg/Day | 3 | 3 | 100.0% |
| Part 1: Cohort 4; 1200 mg/Day | 2 | 6 | 33.3% |
| Part 1 and 2: Cohort 5; 1600 mg/Day | 10 | 33 | 30.3% |
| Part 3: PLX3397 600 mg BID | 5 | 7 | 71.4% |
| Part 3: Paclitaxel 80 mg/m^2 | 2 | 5 | 40.0% |
| Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2 | 3 | 6 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part 1: Cohort 1; 600 mg/Day | 1 of 9 |
| Part 1: Cohort 2; 800 mg/Day | 0 of 3 |
| Part 1: Cohort 3; 1000 mg/Day | 1 of 3 |
| Part 1: Cohort 4; 1200 mg/Day | 1 of 6 |
| Part 1 and 2: Cohort 5; 1600 mg/Day | 5 of 33 |
| Part 3: PLX3397 600 mg BID | 1 of 7 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part 1: Cohort 1; 600 mg/Day | 9 of 9 |
| Part 1: Cohort 2; 800 mg/Day | 3 of 3 |
| Part 1: Cohort 3; 1000 mg/Day | 3 of 3 |
| Part 1: Cohort 4; 1200 mg/Day | 6 of 6 |
| Part 1 and 2: Cohort 5; 1600 mg/Day | 33 of 33 |
| Part 3: PLX3397 600 mg BID | 7 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Part 1: Cohort 1; 600 mg/Day | Part 1: Cohort 2; 800 mg/Day | Part 1: Cohort 3; 1000 mg/Day | Part 1: Cohort 4; 1200 mg/Day | Part 1 and 2: Cohort 5; 1600 mg/Day | Part 3: PLX3397 600 mg BID |
|---|---|---|---|---|---|---|---|
| Tooth infection | Infections and infestations | 0 of 9 | 0 of 3 | 1 of 3 | 1 of 6 | 0 of 33 | 0 of 7 |
| Pneumonia | Infections and infestations | 0 of 9 | 0 of 3 | 0 of 3 | 0 of 6 | 1 of 33 | 1 of 7 |
| Pyrexia | General disorders | 1 of 9 | 0 of 3 | 0 of 3 | 0 of 6 | 1 of 33 | 0 of 7 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 9 | 0 of 3 | 1 of 3 | 0 of 6 | 1 of 33 | 0 of 7 |
| Blood bilirubin increased | Investigations | 0 of 9 | 0 of 3 | 0 of 3 | 0 of 6 | 1 of 33 | 1 of 7 |
| Fatigue | General disorders | 0 of 9 | 0 of 3 | 0 of 3 | 0 of 6 | 0 of 33 | 2 of 7 |
| Abscess | Infections and infestations | 0 of 9 | 0 of 3 | 1 of 3 | 0 of 6 | 0 of 33 | 0 of 7 |
| Cellulitis | Infections and infestations | 0 of 9 | 0 of 3 | 1 of 3 | 0 of 6 | 0 of 33 | 0 of 7 |
| Clostridium difficile colitis | Infections and infestations | 0 of 9 | 0 of 3 | 0 of 3 | 0 of 6 | 1 of 33 | 0 of 7 |
| Device-related sepsis | Infections and infestations | 0 of 9 | 1 of 3 | 0 of 3 | 0 of 6 | 0 of 33 | 0 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part 1: Cohort 1; 600 mg/Day | Part 1: Cohort 2; 800 mg/Day | Part 1: Cohort 3; 1000 mg/Day | Part 1: Cohort 4; 1200 mg/Day | Part 1 and 2: Cohort 5; 1600 mg/Day | Part 3: PLX3397 600 mg BID |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 7 of 9 | 3 of 3 | 1 of 3 | 5 of 6 | 23 of 33 | 3 of 7 |
| Anaemia | Blood and lymphatic system disorders | 7 of 9 | 2 of 3 | 1 of 3 | 2 of 6 | 22 of 33 | 2 of 7 |
| Nausea | Gastrointestinal disorders | 4 of 9 | 1 of 3 | 2 of 3 | 4 of 6 | 14 of 33 | 5 of 7 |
| Decreased appetite | Metabolism and nutrition disorders | 7 of 9 | 1 of 3 | 0 of 3 | 4 of 6 | 12 of 33 | 3 of 7 |
| Diarrhoea | Gastrointestinal disorders | 3 of 9 | 1 of 3 | 2 of 3 | 3 of 6 | 13 of 33 | 4 of 7 |
| Aspartate aminotransferase increased | Investigations | 0 of 9 | 2 of 3 | 1 of 3 | 2 of 6 | 14 of 33 | 1 of 7 |
| Dysgeusia | Nervous system disorders | 1 of 9 | 0 of 3 | 1 of 3 | 3 of 6 | 12 of 33 | 3 of 7 |
| Vomiting | Gastrointestinal disorders | 3 of 9 | 0 of 3 | 1 of 3 | 2 of 6 | 12 of 33 | 1 of 7 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 9 | 1 of 3 | 0 of 3 | 3 of 6 | 11 of 33 | 2 of 7 |
| Lymphocyte count decreased | Investigations | 1 of 9 | 2 of 3 | 1 of 3 | 2 of 6 | 12 of 33 | 1 of 7 |
Serious events with the highest arm-level rate: tooth infection (33.3%), abscess (33.3%), cellulitis (33.3%), device-related sepsis (33.3%), sudden cardiac death (33.3%).
The serious adverse-event data are presented as counts of participants affected and participants at risk in each listed group. For instance, the Part 1 Cohort 2, 800 mg/Day group records 1 affected among 3 at risk, while Part 1 Cohort 4, 1200 mg/Day records 2 among 6. These figures are descriptive of the recorded groups and should not be converted into a comparative treatment conclusion.
The registry separately lists other adverse-event counts, with every participant at risk in each group recorded as affected. These entries are not the same as the primary endpoint’s preferred-term results. The record lists deaths separately; it does not state in this information whether they were treatment-related or provide causes. Serious adverse-event terms reported as 33.3% include Tooth infection, Abscess, Cellulitis, Device-related sepsis, Sudden cardiac death, and Febrile neutropenia. The record does not identify the group or denominator associated with each term percentage.
General statistical context: serious events, any adverse events, and deaths are distinct outcomes and should not be conflated. A recorded event during a study is not automatically attributable to treatment. Group sizes and follow-up context also matter, especially when groups are small. The non-randomized design does not support reading the listed groups as a balanced comparative safety experiment.
12. What the Result Does, and Does Not, Mean
The record describes a study intended to examine safety and tolerability while escalating PLX3397 doses with weekly paclitaxel, confirm a recommended Phase 2 dose, and explore efficacy in a specified Part 3 population. It provides a primary safety endpoint definition and group-level adverse-event counts. It does not report the preferred-term results for the primary endpoint, so those results cannot establish which qualifying events were observed or how frequently they occurred.
The serious-event counts and listed event-term percentages provide descriptive safety information. They do not, alone, show that PLX3397 or paclitaxel caused an event. The death counts are not accompanied by cause or treatment attribution in the registry record described. The record also does not report the primary endpoint’s confidence intervals or an analysis that would support a comparative estimate.
The design matters: the study was non-randomized, open-label, and described as single-group. Although adverse-event listings include groups with different treatments and doses, they are not a randomized control comparison. Differences across such groups could reflect participant or cohort differences, dose, cancer setting, or other influences. The record does not report enough detail to adjust for these factors or to support a causal contrast.
General statistical context: a descriptive safety record can identify events that warrant attention in the setting studied, but it is not equivalent to proof of either benefit or lack of benefit. Likewise, an absent result in the registry record should not be read as evidence that no event occurred. The registry reports efficacy outcomes among its secondary measures, but their results are not reported in the record.
The appropriate interpretation is therefore limited: the study’s design and outcome definitions can be described, and the posted adverse-event counts can be read as recorded counts in their named groups. The registry record does not establish comparative effectiveness, treatment causality for the listed events, or the outcomes of the primary endpoint.
13. Why This Trial Matters Statistically
This study illustrates the statistical distinction between an early-phase safety objective and a comparative treatment-effect question. Its stated aims include exploring tolerability across escalating doses and identifying a recommended Phase 2 dose. Those aims call for careful description of exposure and adverse events, but the non-randomized design does not provide the same basis for causal comparison as a randomized trial.
The study also spans different cohorts and clinical settings. Parts 1 and 2 involve advanced solid tumors, while Part 3 focuses on specified platinum-resistant or -refractory cancers. The primary endpoint applies to Parts 1 and 2, whereas some secondary outcomes are specific to Part 3. Keeping the population and outcome aligned is essential: a result in one cohort or endpoint should not be generalized automatically to another.
The difference between an endpoint definition and an endpoint result is particularly important. The registry specifies the primary safety measure and its reporting threshold, but does not report the preferred-term results. A clear endpoint definition alone cannot tell readers which adverse events were observed or how precise those estimates were. The separately listed serious-event counts answer a different descriptive question.
General statistical context: early-phase studies often generate information useful for planning later research, but their findings should be interpreted in light of cohort size, design, and uncertainty. Here, the record does not report the trial’s sample-size justification or the primary endpoint’s inferential results. Recognizing these limits helps distinguish the study’s stated goals from conclusions that the posted data can support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary endpoint is defined, but its preferred-term results are not reported in the registry record. No endpoint-level percentages, counts, or precision estimates are available for that outcome in the record described. The serious adverse-event listings do not fill this gap because they are a separate safety summary and do not reproduce the primary endpoint’s results.
The non-randomized, open-label design limits causal interpretation. The registry describes the study overall as single-group, and its adverse-event groups include different doses, study parts, and treatment listings. They should not be treated as randomized, like-for-like controls. The record does not report a method for adjusting comparisons across those groups.
The cohorts also differ in their stated clinical context: Parts 1 and 2 concern advanced solid tumors, while Part 3 concerns specified platinum-resistant or -refractory cancers. Findings from one part would not automatically apply to another. The registry record does not report the detailed cohort characteristics needed to assess how participants differed across these settings.
The meaning of the death counts is limited by the absence of cause and treatment attribution in the record described. The listed serious adverse-event term percentages are not linked to a group or denominator in that information. The record also does not report detailed missing-data methods, analysis-population definitions beyond the named populations, multiplicity procedures, or the trial’s sample-size justification.
Finally, the record lists secondary efficacy and pharmacokinetic outcomes but does not report their results in the information described. These limitations prevent a full assessment of efficacy, the precision of the primary safety endpoint, or comparative safety. They do not imply that an unreported result was null or that an unlisted event did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors — NCT01525602.
- Registry record last updated 2020-07-16; status last verified 2020-07.
- Results first posted 2020-07-16.
- 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.
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18. Record Summary
The registry record describes a completed phase 1b, non-randomized, open-label study of PLX3397 with weekly paclitaxel in advanced solid tumors. It lists 74 enrolled participants and three parts: dose escalation, an extension cohort at the recommended Phase 2 dose, and a cohort focused on specified platinum-resistant or -refractory cancers.
The primary endpoint measures the percentage of the Parts 1 and 2 Safety Population with treatment-emergent adverse events by preferred term, for terms reported by more than 10% of participants. The registry record does not report those primary endpoint results. It separately lists serious adverse-event counts, other adverse-event counts, and deaths by group, without treatment attribution for deaths in the record described.
The study also lists secondary efficacy, pharmacokinetic, and safety outcomes. Their results, the statistical analysis plan, multiplicity methods, missing-data methods, and sample-size justification are not reported in the registry record. Because the study is non-randomized, its group listings do not establish a randomized treatment comparison.