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 ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer (NCT03449901), a non-randomized phase 2 study. The primary outcome is Progression-free Survival (PFS) (Cohort 1 Only).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03449901 |
| Phase | Phase 2 |
| Condition | Soft Tissue Sarcoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 98 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled people in a study of treatment for soft tissue sarcoma and included an exploratory Cohort 2 for people with osteosarcoma, Ewing's sarcoma, or small cell lung cancer. The registry lists soft tissue sarcoma as the condition. The brief summary describes the additional Cohort 2 diagnoses and its intended composition: ten people with osteosarcoma or Ewing's sarcoma, ideally five with each diagnosis, and five with small cell lung cancer. Those figures describe the exploratory cohort's intended composition, not necessarily the final number enrolled in each diagnosis group. Total enrollment was 98.
Intervention
Both cohorts received the combination of ADI-PEG 20, gemcitabine, and docetaxel. The brief summary frames the study around whether adding ADI-PEG 20 to gemcitabine and docetaxel could improve clinical benefit in soft tissue sarcoma, and describes the additional diagnoses as exploratory. The record also lists tumor biopsy and research blood draw as procedures. Detailed dosing information for gemcitabine and docetaxel is not reported in the registry record.
Comparator
There was no randomized control group. The registry identifies the allocation as non-randomized and describes parallel cohorts. Both cohorts received the three-drug combination, so the record does not describe a like-for-like comparison of the combination against a different treatment or against no treatment. Differences between the cohorts, including their diagnoses and the listed gemcitabine dose levels, should not be interpreted as randomized treatment effects.
Primary question
The primary outcome was progression-free survival in Cohort 1 only. It measures time from study entry to progression or death, with latest follow-up used when progression or death had not been observed. The statistical question is how long participants in that cohort remained alive without recorded progression, and how precisely that duration was estimated. The registry identifies the measure as a median with a 95% confidence interval, but the median and interval are not reported in the registry record. Cohort 2 was not analyzed for this outcome.
3. Trial Design
This was a phase II, non-randomized, unmasked trial with a parallel-cohort structure. The registry lists Washington University School of Medicine as sponsor, gives a total enrollment of 98, and marks the study as completed. The recorded start date is 2018-05-09 and the primary completion date is 2022-07-08. These dates describe the registry record; they do not by themselves establish how long any individual participant was followed.
The study evaluated ADI-PEG 20 in combination with gemcitabine and docetaxel. Cohort 1 was the soft tissue sarcoma cohort and was the only cohort included in the primary progression-free survival outcome. Cohort 2 was described as exploratory and included osteosarcoma, Ewing's sarcoma, and small cell lung cancer. The summary says enrollment to Cohort 2 would occur concurrently with Cohort 1. It also gives an intended composition for Cohort 2, but the final number enrolled in each diagnosis group is not reported in the registry record.
Non-randomized allocation means participants were not assigned by chance to a treatment and control arm for a comparative efficacy question. The adverse-event record separates participants by cohort and gemcitabine dose level, but those groupings do not constitute randomized comparisons. The record lists no masking. It does not describe a separate control intervention, and the intervention listed for each cohort is the same three-drug combination.
The brief summary explains the rationale as a combination strategy involving arginine depletion and two anticancer drugs. That rationale is background, not an outcome result. The registry record does not report a protocol-based sample-size justification, detailed allocation procedures, or a statistical analysis plan. The listed primary outcome is a median time-to-event measure with a 95% confidence interval; the result itself is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 1 patient was enrolled, but never initiated treatment.
Overall Study
| Stage | Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel |
|---|---|---|
| STARTED | 82 | 15 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 81 | 15 |
Reasons for not completing this period:
| Reason | Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel |
|---|---|---|
| Progression | 57 | 12 |
| Adverse Event | 3 | 0 |
| Death | 6 | 2 |
| Withdrawal by Subject | 12 | 1 |
| Physician Decision | 1 | 0 |
| Patient elected for surgical intervention | 1 | 0 |
| Patient off for other complicating disease | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: PFS was evaluated only for Cohort 1; therefore, no participants in Cohort 2 were analyzed for this outcome measure. 2 participants in Cohort 1 were not evaluable for this outcome measure.
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.
| Characteristic | Unit | Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel | Total |
|---|---|---|---|---|
| Participants analysed | 82 | 15 | 97 | |
| Age, Continuous | years | 57 (16 to 86) | 30 (12 to 71) | 55 (12 to 86) |
| Sex: Female, Male: Female | Participants | 45 | 7 | 52 |
| Sex: Female, Male: Male | Participants | 37 | 8 | 45 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 | 0 | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 78 | 13 | 91 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 2 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 5 | 0 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 1 | 7 |
| Race (NIH/OMB): White | Participants | 71 | 11 | 82 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 3 | 3 |
| Region of Enrollment: United States | participants | 82 | 15 | 97 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS) (Cohort 1 Only), measured over Through completion of follow-up (median follow-up 494 days, full range of 5-1500 days)..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival, or PFS, is the primary outcome for Cohort 1. The registry defines it as time on study until progression on the drug combination or death. If neither event had been observed by the latest follow-up, that latest follow-up time was used. Progression was defined using changes in the sum of target-lesion diameters: at least a 20% increase relative to the smallest sum on study, together with an absolute increase of at least 5 mm. The appearance of one or more new lesions also counted as progression.
PFS is used in clinical trials to describe the time until a participant experiences either disease progression or death. Combining these events gives a time-to-event outcome that accounts for when events occur, rather than recording only whether an event happened by a particular visit. The median is the point in the estimated time distribution at which half the population's survival experience lies on either side. A 95% confidence interval communicates uncertainty around that estimate; it does not describe the range of individual participants' survival times.
The registry states that PFS was evaluated only in Cohort 1. No Cohort 2 participants were analyzed for this outcome, and two Cohort 1 participants were not evaluable. The stated timeframe is through completion of follow-up, with median follow-up of 494 days and a full range of 5-1500 days. The PFS median and its confidence interval are not reported in the registry record, so the size and precision of the estimated PFS cannot be assessed from the recorded results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically relevant time-to-event outcome, but it does not report the primary PFS estimate. In particular, it gives no median PFS value or 95% confidence interval. Without those results, the duration of PFS observed in Cohort 1 and the precision of its estimate cannot be described. The endpoint definition and follow-up information explain what the analysis was intended to measure, but they do not substitute for the outcome estimate.
The analysis population was restricted to Cohort 1. Cohort 2 was not analyzed for PFS, so the primary outcome cannot be interpreted as evidence across all diagnoses enrolled in the trial. Two people in Cohort 1 were not evaluable for PFS. The registry does not report why they were not evaluable, how they were handled in the analysis, or the number included in the PFS calculation. These details matter because time-to-event estimates depend on the population analyzed and on how observed events and incomplete follow-up are treated.
The overall enrollment was 98, but that total does not tell readers how many people contributed to the primary PFS analysis. It should not be treated as the PFS analysis denominator. The listed adverse-event groups distinguish Cohort 1 dose levels and a Cohort 2 dose level, but they are not control arms. The non-randomized design does not support attributing differences between these groups to dose or cohort characteristics without additional design and analysis information.
Follow-up is described as having a median of 494 days, with a full range of 5-1500 days. In general, follow-up duration affects how much information is available about later events: participants with shorter observation may have an event time that remains unknown at the end of follow-up. A time-to-event analysis can account for this kind of incomplete event observation, but the exact methods used in this trial are not reported in the registry record.
The record lists secondary outcomes including overall survival, clinical benefit rate, safety and tolerability, and cancer-related mortality, with several explicitly restricted to Cohort 1. It does not report numerical results for those outcomes in the registry record for this account. The adverse-event record does list serious-event counts and selected serious-event terms. Those data describe reported safety experience, not comparative efficacy. Because there is no randomized comparator, neither the safety listings nor the primary endpoint description establish what would have happened under another treatment.
Consequently, the statistical interpretation is constrained by missing outcome estimates and analysis details. The registry record supports describing the trial design, endpoint definition, follow-up, and listed adverse events. It does not support a numerical conclusion about PFS, a comparison with standard care, or a causal claim about the effect of adding ADI-PEG 20.
9. Statistical Methods Explained
Time-to-event outcomes record both whether an event occurred and the time at which it occurred. For PFS, the event is progression or death, according to the registry definition. When a participant has not had either event by the last known follow-up, the observation is incomplete rather than an event-free time known indefinitely. General time-to-event methods can retain such observations up to their last follow-up, using censoring to represent that the event time is not known beyond that point. The precise method used for the trial's PFS estimate is not reported in the registry record.
What does a median time-to-event estimate mean?
A median summarizes the time distribution rather than an average of all observed times. It is commonly used when follow-up is incomplete or when the distribution of event times is not well represented by a simple average. In general, the median time is the point where the estimated proportion remaining event-free reaches one half. The registry names the median as the PFS summary measure, but does not give its value. Therefore, no numerical median or interpretation of its magnitude can be made from the registry record.
What does the confidence interval contribute?
A confidence interval communicates statistical uncertainty in an estimate. For a median PFS estimate, the 95% confidence interval would indicate a range of values compatible with the estimation procedure and observed data, under its assumptions. It is not a range containing 95% of individual participants' PFS times, and it is not a guarantee about a future study. The registry says the PFS estimate was to be reported with a 95% confidence interval, but neither endpoint of that interval nor the median is reported in the registry record. Consequently, the precision of the estimate cannot be judged.
Why does follow-up matter?
The stated follow-up has a median of 494 days and a full range of 5-1500 days. This describes the follow-up duration across participants, not the time to progression or death. In general, longer observation can make later events observable, whereas shorter observation can leave event times censored. A median follow-up summary does not disclose how many events occurred, how many participants remained at risk at different times, or the shape of the PFS curve. Those details are not reported in the registry record.
Why are the cohorts not a treatment comparison?
The allocation is non-randomized, and both cohorts received ADI-PEG 20, gemcitabine, and docetaxel. Randomization is a design method for balancing, on average, known and unknown participant characteristics across treatment groups. Without randomized assignment to a control intervention, the two cohorts cannot be treated as an experimental and control arm comparison. Their differing diagnoses and dose-level groupings further mean that a simple contrast could reflect differences in who was enrolled or in other aspects of care, rather than a treatment effect. The registry record does not describe a comparative analysis capable of resolving these issues.
The sponsor's rationale discusses biological mechanisms and prior observations, but those statements are not results of the PFS analysis. The current statistical description must distinguish a proposed mechanism from evidence generated by the trial. No hazard ratio or other comparative effect estimate is reported in the registry record.
How should planning illustrations be read?
General sample-size illustrations are planning calculations, not descriptions of what the trial observed and not estimates of observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect targeted is a stated fraction of an observed effect. For time-to-event outcomes, the illustration concerns the total number of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. Those assumptions describe a calculation framework, not the trial's own design justification. The protocol's sample-size justification is not reported in the registry record. No numerical planning values or observed effect estimates are reported in the registry record, so no planning result can be interpreted.
More generally, sample size calculations depend on the assumed effect, variability or event rate, significance threshold, allocation, and analysis method. A planning illustration based on an effect observed in a trial can be useful for exploring hypothetical future designs, but it should not be read as the power achieved in the completed trial. The actual number of participants contributing to an endpoint and the amount of event information are separate considerations.
What can the reported safety counts establish?
Adverse-event counts are descriptive. The record presents numbers at risk and numbers affected within several cohort and gemcitabine dose-level groups, as well as deaths and selected serious-event terms. A count does not alone convey event timing, duration, severity beyond the relevant classification, or whether participants had more than one event. The method used to attribute events to treatment, summarize repeated events, or handle missing safety observations is not reported in the registry record. Since the trial is non-randomized and does not include a listed control group, these safety data cannot by themselves establish comparative risk.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists PFS in Cohort 1 as the primary outcome and identifies secondary outcomes including overall survival, clinical benefit rate, safety and tolerability, and cancer-related mortality. Several secondary outcomes are explicitly labeled for Cohort 1 only. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if each is tested separately. General approaches to multiplicity include prespecifying a primary outcome, adjusting significance thresholds, or treating secondary analyses as exploratory. Which approach was used for this trial is not reported in the registry record.
The record does not report a statistical analysis plan, an interim-analysis plan, or any adjustment for multiple comparisons. It also does not provide numerical PFS results, secondary-outcome estimates, or associated uncertainty measures in the registry record for this account. Therefore, no claims about statistical significance or the handling of multiple testing can be made.
For PFS, the registry states that Cohort 2 was not analyzed and two Cohort 1 participants were not evaluable. The reasons for non-evaluability, the analysis denominator, and the rules for censoring or excluding observations are not reported in the registry record. General missing-data methods depend on why data are absent and on the estimand being targeted; the registry does not give enough information to assess those assumptions for this outcome.
The registry specifies the PFS population as Cohort 1, but does not describe a broader analysis-population definition, such as whether participants were analyzed according to enrollment, treatment receipt, or evaluability rules. It also does not report the analysis population for each secondary outcome. These omissions limit reproducibility and make it difficult to determine exactly which participants contributed to each result. The enrollment total should not be mistaken for an endpoint-specific analysis count.
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 |
|---|---|---|---|
| Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 14 | 33 | 42.4% |
| Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 8 | 25 | 32.0% |
| Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 13 | 24 | 54.2% |
| Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 5 | 15 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 19 of 33 |
| Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 15 of 25 |
| Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 19 of 24 |
| Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 12 of 15 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 33 of 33 |
| Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 25 of 25 |
| Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 24 of 24 |
| Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 15 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel |
|---|---|---|---|---|---|
| Febrile Neutropenia | Blood and lymphatic system disorders | 3 of 33 | 3 of 25 | 1 of 24 | 1 of 15 |
| Sepsis | Infections and infestations | 0 of 33 | 3 of 25 | 4 of 24 | 1 of 15 |
| Lung Infection | Infections and infestations | 1 of 33 | 1 of 25 | 2 of 24 | 1 of 15 |
| Skin Infection | Infections and infestations | 1 of 33 | 0 of 25 | 2 of 24 | 1 of 15 |
| Pleural Effusions | Respiratory, thoracic and mediastinal disorders | 3 of 33 | 0 of 25 | 0 of 24 | 1 of 15 |
| Anemia | Blood and lymphatic system disorders | 1 of 33 | 1 of 25 | 1 of 24 | 0 of 15 |
| Disease Progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 33 | 0 of 25 | 2 of 24 | 0 of 15 |
| Atrial Fibrillation | Cardiac disorders | 0 of 33 | 1 of 25 | 1 of 24 | 0 of 15 |
| Small Intestinal Obstruction | Gastrointestinal disorders | 2 of 33 | 0 of 25 | 0 of 24 | 0 of 15 |
| Enterocolitis Infectious | Infections and infestations | 1 of 33 | 0 of 25 | 0 of 24 | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 29 of 33 | 19 of 25 | 23 of 24 | 13 of 15 |
| Platelet Count Decreased | Investigations | 28 of 33 | 23 of 25 | 21 of 24 | 11 of 15 |
| White Blood Cell Decreased | Investigations | 25 of 33 | 22 of 25 | 20 of 24 | 11 of 15 |
| Lymphocyte Count Decreased | Investigations | 24 of 33 | 18 of 25 | 24 of 24 | 10 of 15 |
| Neutrophil Count Decreased | Investigations | 25 of 33 | 19 of 25 | 17 of 24 | 10 of 15 |
| Fatigue | General disorders | 23 of 33 | 22 of 25 | 18 of 24 | 5 of 15 |
| Alkaline Phosphatase Increased | Investigations | 13 of 33 | 12 of 25 | 13 of 24 | 6 of 15 |
| Alanine Aminotransferase Increased | Investigations | 14 of 33 | 14 of 25 | 11 of 24 | 4 of 15 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 15 of 33 | 8 of 25 | 15 of 24 | 3 of 15 |
| Hypocalcemia | Metabolism and nutrition disorders | 15 of 33 | 7 of 25 | 12 of 24 | 4 of 15 |
Serious events with the highest arm-level rate: sepsis (16.7%), febrile neutropenia (12.0%), pleural effusions (9.1%), lung infection (8.3%), skin infection (8.3%).
The safety record separates adverse-event information by cohort and gemcitabine dose level. For the Cohort 1 600mg/m2 dose level, 33 participants were at risk for serious adverse events and 14 were affected; for the 750 mg/m2 dose level, the corresponding counts were 25 and 8; for the 900 mg/m2 dose level, they were 24 and 13. For Cohort 2 at the 600mg/m2 dose level, 15 were at risk and 5 were affected. These are descriptive counts within the listed groups, not comparisons against a control treatment.
The record also lists deaths of 19, 15, 19, and 12 in those respective groups. It does not specify in the registry record for this account how these deaths relate to treatment, whether they were cancer-related, or how follow-up differed across groups. They should not be interpreted as treatment-attributable deaths.
Selected serious adverse-event terms are listed with percentages: Sepsis, 16.7%; Febrile Neutropenia, 12.0%; Pleural Effusions, 9.1%; Lung Infection, 8.3%; Skin Infection, 8.3%; and Disease Progression, 8.3%. The record does not provide the denominator or detailed event-counting rules for each listed percentage in the registry record. Participants may also experience more than one event, so event terms should not be treated as mutually exclusive categories. The non-randomized design and absence of a listed control arm preclude a like-for-like safety comparison.
12. What the Result Does, and Does Not, Mean
The trial addresses a combination regimen in a phase II setting and defines PFS as its primary outcome for Cohort 1. Its registry record offers information about the study structure, target populations, endpoint definition, follow-up description, and selected adverse-event listings. These details help readers understand what the investigators intended to measure and the limits of the design.
The central efficacy result cannot be interpreted because the PFS median and its 95% confidence interval are not reported in the registry record. No hazard ratio, PFS event count, or other numerical efficacy estimate is available in the registry record used for this account. As a result, the data do not establish the observed duration of PFS or the precision of an estimate. They also do not support a numerical comparison with another regimen.
The study was non-randomized and does not list a control intervention. A result from a single treated cohort can describe outcomes among those participants, but without a suitable comparison it cannot isolate the effect of ADI-PEG 20 from the effects of gemcitabine and docetaxel, participant characteristics, disease course, or other influences. Cohort 2 is exploratory and was not included in the primary PFS analysis. Its diagnoses and intended composition should not be conflated with the Cohort 1 population.
The serious adverse-event data are descriptive group counts and selected terms. They can communicate that serious events were recorded, but they do not on their own establish comparative safety or treatment causation. The record does not provide all details needed to interpret event attribution, timing, or denominators for the selected terms.
Overall, the registry record supports a careful description of a completed, non-randomized phase II study and its outcome definitions. It does not support a conclusion that the combination improves clinical benefit, changes PFS relative to another treatment, or produces a particular comparative safety profile. Such conclusions require results and design information that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why the design of a trial determines the kinds of statistical conclusions that can be drawn. A phase II, non-randomized study can describe outcomes under a regimen and contribute information about feasibility and safety. It is not equivalent to a randomized comparison, because there is no chance-based assignment to balance participant characteristics across treatment groups. In this trial, both cohorts received the same combination, and the cohorts differ in their described diagnoses.
It also highlights the importance of outcome reporting. PFS is carefully defined, including the progression criteria and the use of death or latest follow-up in the time-to-event measure. Yet the median and confidence interval are not reported in the registry record. Endpoint definitions are essential for interpreting a result, but they cannot replace the result itself. Without the estimate and its uncertainty, readers cannot judge either the observed magnitude or precision.
The separation between an overall enrollment count and an endpoint-specific analysis population is another important statistical issue. The record reports enrollment of 98, but says two Cohort 1 participants were not evaluable for PFS and excludes Cohort 2 from that outcome. Endpoint-specific denominators and analysis rules are necessary for understanding who contributed information and how missing observations were handled.
Finally, safety counts require context. Group-specific counts and selected serious-event terms are informative descriptions, but non-randomized groups do not provide an unbiased control comparison. The record also lacks details about event attribution and the denominator behind listed percentages. These limitations show why transparent reporting of methods, analysis populations, event definitions, and uncertainty is central to sound interpretation of clinical research.
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 limitation for interpreting efficacy is that the registry record does not report the Cohort 1 PFS median or its 95% confidence interval. It also does not report the number of PFS events, a survival curve, or a comparative effect estimate. Accordingly, neither the size nor the precision of the primary result can be assessed.
The design is non-randomized and has no listed control group. Although the study has parallel cohorts and adverse-event groupings at different gemcitabine dose levels, these are not randomized comparator arms. Differences across groups may reflect cohort composition or other factors, and the registry information does not establish a causal treatment contrast.
The registry states that Cohort 2 was not analyzed for PFS and that two Cohort 1 participants were not evaluable. It does not report the reasons for non-evaluability, the endpoint-specific denominator, the censoring rules, or a detailed analysis-population definition. The intended Cohort 2 composition is described, but the final enrollment by diagnosis is not reported in the registry record.
Follow-up is described by a median and full range, but the record does not give the number of events or detail the distribution of follow-up by cohort. The listed serious adverse-event terms have percentages, but their denominators and event-counting rules are not stated in the registry record. Detailed dosing descriptions for gemcitabine and docetaxel are also not reported in the registry record.
Finally, the registry information does not include a protocol-based sample-size justification, a statistical analysis plan, multiplicity procedures, interim-analysis details, or numerical secondary-outcome results. These omissions constrain reproducibility and interpretation, and should not be filled by assumptions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer — NCT03449901.
- Registry record last updated 2025-12-11; status last verified 2025-11.
- Results first posted 2023-09-08.
- 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
NCT03449901 is a completed, non-randomized phase II trial sponsored by Washington University School of Medicine. Total enrollment was 98. The study evaluated ADI-PEG 20 with gemcitabine and docetaxel in Cohort 1 and an exploratory Cohort 2. The registry lists soft tissue sarcoma as the condition and describes osteosarcoma, Ewing's sarcoma, and small cell lung cancer as additional Cohort 2 diagnoses.
The primary outcome was median PFS with a 95% confidence interval, evaluated only in Cohort 1. The registry defines progression and includes death in the PFS event definition. Two Cohort 1 participants were not evaluable, and no Cohort 2 participants were analyzed for this outcome. The median and confidence interval are not reported in the registry record.
Serious adverse-event counts are listed by cohort and gemcitabine dose level, alongside selected serious-event terms. The non-randomized design does not provide a like-for-like control comparison. The record does not report the analysis plan or the protocol's sample-size justification.