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 Study of the Pan-DAC Inhibitor AR-42 and Pazopanib in Advanced Sarcoma and Kidney Cancer (NCT02795819), a non-randomized phase 1 study. The primary outcome is The Recommended Phase 2 Doses (RP2Ds) of AR-42 and Pazopanib When Given in Combination..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02795819 |
| Phase | Phase 1 |
| Condition | Renal Cell Carcinoma, Soft Tissue Sarcoma, Metastatic Disease |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Virginia Commonwealth University |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced soft tissue sarcoma or renal cell carcinoma were the intended population. The registry also lists metastatic disease among the conditions. The record reports enrollment of 6 participants but does not provide further participant characteristics in the posted results.
Intervention
The study combined AR-42, an oral drug, with oral pazopanib. The sequential dose-escalation plan included several dose combinations, with AR-42 doses ranging from 10 mg to 40 mg and pazopanib doses of 600mg or 800mg daily. The AR-42 schedule was 3 non-consecutive days during the first 3 weeks of each 4-week cycle.
Comparator
There was no randomized control group or like-for-like comparison. Allocation was non-randomized, and the study model was sequential. Dose groups were part of an escalation plan rather than independently assigned treatment arms for a comparative efficacy question.
Primary question
The primary objective was to identify recommended phase 2 doses for AR-42 and pazopanib in combination, based on dose-limiting toxicities during the first treatment cycle and protocol criteria for maximum tolerated doses. The registry reports 2 dose-limiting toxicities among 6 participants treated at the first dose level. The study ended before additional dose levels were explored, so no maximum tolerated dose or recommended phase 2 dose was identified.
The clinical question is therefore about early dose evaluation and tolerability, not a controlled test of whether the combination improves outcomes relative to another treatment. Antitumor effects and treatment-related adverse events were listed as secondary outcomes, but numerical results for those outcomes are not reported in the registry record.
3. Trial Design
This was a phase 1, nonrandomized, unmasked study with a sequential model. Virginia Commonwealth University was the sponsor. The registry reports a start date of 2016-07-08, a primary completion date of 2016-11-24, and a terminated status. Enrollment was 6. These features describe a small early-phase dose-finding study, rather than a randomized comparison designed to estimate comparative efficacy.
The intervention was a combination of AR-42 and pazopanib. The planned cohorts used AR-42 doses of 10 mg, 20 mg, 30 mg, or 40 mg on 3 non-consecutive days during the first 3 weeks of each 4-week cycle. Pazopanib was taken continuously at 600mg or 800mg daily. The registry lists Cohort minus 1 (-1), Cohort 1, Cohort 2, Cohort 3A, Cohort 3B, Cohort 4A, and Cohort 4B. The posted primary outcome states that only the first dose level was treated and that the study stopped before exploration of additional dose levels; the record does not report participants treated in each planned cohort.
The primary outcome concerned recommended phase 2 doses, with dose-limiting toxicity evaluated during the first treatment cycle. A participant without an observed dose-limiting toxicity at the delivered dose needed at least 6 AR-42 doses and at least 21 pazopanib doses during cycle 1 to be considered evaluable. The registry describes summarizing dose levels, dose modifications, evaluability, and dose-limiting toxicities using basic descriptive statistics, such as frequencies and proportions. The protocol criteria used to select the maximum tolerated dose and recommended phase 2 dose are not reported in the registry record.
The record lists renal cell carcinoma and soft tissue sarcoma as conditions, along with metastatic disease. It does not report the distribution of participants across these diagnoses, or other clinical characteristics needed to describe the enrolled population in greater detail.
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 7 groups are shown.
Overall Study
| Stage | Cohort Minus 1 (-1) | Cohort 1 | Cohort 2 | Cohort 3A | Cohort 3B | Cohort 4A |
|---|---|---|---|---|---|---|
| STARTED | 0 | 6 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 6 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Incomplete objective. No maximum tolerated dose (MTD) nor recommended phase two dose (RP2D) identified. Two dose limiting toxicities observed in 6 patients treated at the first dose level. Study terminated prior to exploration of additional dose levels.
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 baseline characteristics subjects were in Cohort 1
| Characteristic | Unit | Cohort 1 |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | Years | 54.8 (38 to 63) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as The Recommended Phase 2 Doses (RP2Ds) of AR-42 and Pazopanib When Given in Combination., measured over 1 month.
| Element | Registry entry |
|---|---|
| Result type | Count Of Units |
| Measure of spread | not applicable |
| Unit | Dose Limiting Toxicities |
| Endpoint classification | not reduced to a single comparison |
The primary outcome was the recommended phase 2 doses of AR-42 and pazopanib when given together. Its unit was dose-limiting toxicities, and the evaluation period was the first treatment cycle, described as 1 month. The endpoint was intended to guide dose selection for later clinical trials by identifying doses considered tolerable under the study protocol. In dose-finding research, dose-limiting toxicities help distinguish dose levels according to short-term tolerability; the protocol’s criteria are essential because the meaning of a toxicity and the threshold for advancing or selecting a dose depend on prespecified rules.
The record describes participants as evaluable for dose-limiting toxicity only if they received minimum amounts of both drugs during cycle 1 when a toxicity had not already been observed at the delivered dose. It also says dose levels, dose modifications, evaluability, and toxicities would be summarized using frequencies and proportions. The protocol criteria for determining the maximum tolerated dose and recommended phase 2 dose are not reported in the registry record.
The posted result is incomplete for the intended dose-selection objective. It reports 2 dose-limiting toxicities among 6 participants treated at the first dose level, and states that the study was terminated before additional dose levels were explored. No maximum tolerated dose or recommended phase 2 dose was identified. The outcome therefore records an unresolved dose-finding question, rather than a selected dose for subsequent study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central result is limited but clear: 2 dose-limiting toxicities were observed among 6 participants treated at the first dose level, and the study ended before additional dose levels were explored. The registry explicitly labels the primary outcome incomplete and reports that neither a maximum tolerated dose nor a recommended phase 2 dose was identified. Thus, the posted findings do not establish a dose for later-phase testing.
Because the study was nonrandomized and sequential, its dose groups do not form a randomized treatment comparison. There is no control group against which to estimate a comparative effect, and the record does not report an efficacy estimate or inferential analysis. Antitumor effects were listed as a secondary outcome, but numerical results for that outcome are not reported in the registry record. The same applies to the listed secondary outcome concerning treatment-related adverse events: the registry includes safety counts and serious-event terms, but does not report a comparative analysis.
The small enrollment and early termination constrain how much can be learned from the observed toxicity count. In a small group, each participant’s outcome has substantial influence on a frequency or proportion. Such a count can describe what was observed among the treated participants, but it does not by itself establish the underlying frequency of toxicity in a broader population. A confidence interval, which expresses uncertainty around an estimated quantity, is not reported for this primary outcome.
The registry’s safety data list 6 participants at risk in Cohort 1, 2 participants with serious adverse events, 6 with other adverse events, and 1 death. These are descriptive safety figures. The record does not establish from these counts alone whether the death was related to treatment or whether the serious adverse events were dose-limiting toxicities. The serious adverse-event terms are each listed with 16.7%; those terms should not be added together or treated as independent participants without information about event overlap.
The trial’s termination and incomplete dose exploration are important context for all interpretations. The observed dose-limiting toxicities belong to the first dose level only. They do not show what would have occurred at the other planned dose levels, and the record does not support conclusions about comparative benefit or the best dose. Any conclusions should remain within the descriptive scope of the posted results.
Planning illustrations based on an observed effect are not observed power. Their stated assumptions include 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 the observed effect. These are planning assumptions, not a report of the trial’s design rationale. The record does not report that the trial used a two-arm randomized design or that these assumptions informed its conduct.
9. Statistical Methods Explained
The primary outcome is a dose-finding objective, not a conventional comparison of average outcomes between treatment groups. It asks which combination dose should be recommended for later study, with dose-limiting toxicities in the first treatment cycle serving as key evidence. The registry describes a sequential study in which participants received successive dose levels according to the study plan. In general, sequential escalation designs use accumulated safety information to guide whether dose levels are explored or selected. The specific decision rules for this study are not reported in the registry record, so the escalation decisions cannot be reconstructed from the posted information.
The posted primary result is a count: 2 dose-limiting toxicities among 6 participants at the first dose level. A count is a direct description of observed events or participants, depending on the unit defined by the outcome. The registry’s outcome unit is dose-limiting toxicities, while its result description phrases the finding as toxicities observed in participants. It does not provide a participant-level listing, timing by participant, or further details of the toxicities. The report therefore supports describing the observed count, but not a more detailed analysis of who experienced which event or how events were distributed over time.
Frequencies and proportions are descriptive methods mentioned for summarizing dose level, dose modification, evaluability, and dose-limiting toxicities. A frequency reports a count; a proportion relates a count to a relevant group size. Descriptive summaries are useful for showing what happened in a small dose-finding study. They do not, by themselves, quantify uncertainty or establish a causal treatment effect. The registry does not report confidence intervals or a statistical test for the primary result.
A confidence interval is a general statistical method for expressing uncertainty around an estimate. It gives a range of values compatible with the data under a specified method and assumptions. With a small number of participants, interval estimates can be wide, reflecting limited precision. No confidence interval for the dose-limiting toxicity result is reported in the registry record, so the precision of an estimated toxicity frequency cannot be assessed from an interval in the posted results.
Some outcomes in clinical studies can be over-dispersed: their variability is greater than a simple model assumes. In general, over-dispersion can make standard errors too small if it is ignored, leading to confidence intervals that are too narrow and tests that appear more decisive than warranted. This concept is relevant when choosing models for count outcomes, but the registry does not report a model-based analysis of the primary outcome or any assessment of over-dispersion. No claim about over-dispersion in these data is supported.
The registry’s evaluability rule is part of interpreting the primary endpoint. When no dose-limiting toxicity had been observed at the delivered dose, a participant needed at least 6 AR-42 doses and at least 21 pazopanib doses during cycle 1 to be considered evaluable. Such rules matter because participants who receive too little treatment may not have had the intended opportunity for toxicity evaluation. The record does not report how many participants met this rule, how any nonevaluable participants were handled, or whether all 6 participants contributed to every primary outcome summary.
The outcome description says dose-level information, modifications, evaluability, and toxicities would be summarized with basic descriptive statistics. It also states that maximum tolerated doses and recommended phase 2 doses would be determined using protocol criteria. Those criteria and the actual dose-selection procedure are not reported in the registry record. As a result, the reader cannot independently apply the protocol’s decision rules to the observed events or determine what additional evidence would have been needed to select a dose.
Planning calculations are distinct from the trial’s observed analysis. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and target effects expressed as fractions of an observed effect. For time-to-event calculations, the stated convention is to give the total number of events using the Schoenfeld method; other planning calculations use participants per arm. These are generic planning conventions for the illustrations, not evidence that the study was randomized, had two comparable arms, or used those calculations to set its enrollment. The registry does not report a sample-size justification for the trial. A planning sample size is not observed power, and it cannot resolve the uncertainty caused by the study ending before dose escalation was completed.
The registry reports 0 analyses. This means no inferential analysis is posted in the record; it does not establish that no analyses were conducted outside the registry. The statistical analysis plan, interim analysis procedures, and detailed model specifications are not reported in the registry record. No additional analysis method should be attributed to the investigators without that information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary dose-selection outcome and secondary outcomes concerning treatment-related adverse events and antitumor effects in participants with advanced renal cell carcinoma or soft tissue sarcoma. It does not report a multiplicity plan for interpreting several outcomes or testing multiple hypotheses. In general, multiplicity arises when multiple statistical questions are addressed; without a prespecified approach, the chance of at least one apparently notable result can increase. No claim about adjusted or unadjusted testing is supported because the registry reports 0 analyses and no testing procedure.
Missing-data handling is not reported in the registry record. The primary outcome description gives a minimum treatment-exposure rule for evaluability when a dose-limiting toxicity has not been observed, but does not say how participants who fail to meet that rule were treated in the summary. The number evaluable, the extent of missing outcome information, and any method for handling missing observations are not reported. In a dose-finding study, this distinction matters because an absence of a recorded toxicity is not necessarily equivalent to an adequately observed cycle without toxicity.
The analysis populations are not fully described. The record reports enrollment of 6 and says 2 dose-limiting toxicities were observed in 6 participants treated at the first dose level, but it does not provide separate population definitions for safety, efficacy, or primary outcome analyses. It also does not provide participant-level disposition or explain whether all enrolled participants were included in each outcome summary. The evaluability criterion is the only explicit analysis-related population rule in the primary outcome 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 |
|---|---|---|---|
| Cohort 1 | 2 | 6 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 | 1 of 6 |
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 | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 1 of 6 |
| Disseminated Intravascular Coagulation | Blood and lymphatic system disorders | 1 of 6 |
| Cardiac Arrest | Cardiac disorders | 1 of 6 |
| Sinus Tachycardia | Cardiac disorders | 1 of 6 |
| Ventricular Tachycardia | Cardiac disorders | 1 of 6 |
| Abdominal Pain | Gastrointestinal disorders | 1 of 6 |
| Mucositis Oral | Gastrointestinal disorders | 1 of 6 |
| Nausea | Gastrointestinal disorders | 1 of 6 |
| Fatigue | General disorders | 1 of 6 |
| General Disorders administration site conditions - Other, specify | General disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 |
|---|---|---|
| Lymphocyte count decreased | Investigations | 6 of 6 |
| Neutrophil count decreased | Investigations | 5 of 6 |
| White blood cell decreased | Investigations | 5 of 6 |
| Anorexia | Metabolism and nutrition disorders | 5 of 6 |
| Nausea | Metabolism and nutrition disorders | 5 of 6 |
| Abdominal pain | Gastrointestinal disorders | 4 of 6 |
| Bloating | Gastrointestinal disorders | 4 of 6 |
| Malaise | General disorders | 4 of 6 |
| Pain | General disorders | 4 of 6 |
| Alanine aminotransferase increased | Investigations | 4 of 6 |
Serious events with the highest arm-level rate: anemia (16.7%), disseminated intravascular coagulation (16.7%), cardiac arrest (16.7%), sinus tachycardia (16.7%), ventricular tachycardia (16.7%).
The registry reports a safety group labeled Cohort 1, with 6 participants at risk. It lists 2 participants with serious adverse events, 6 with other adverse events, and 1 death. These are counts in the posted safety record; they should not be interpreted as a randomized comparison or as estimates of comparative risk. The record does not identify a control group.
The listed serious adverse-event terms are Anemia, Disseminated Intravascular Coagulation, Cardiac Arrest, Sinus Tachycardia, Ventricular Tachycardia, and Abdominal Pain. Each term is reported as 16.7%. The record does not establish from this list whether the terms occurred in different participants, whether one participant experienced more than one term, or whether each event was considered related to treatment. The percentages therefore should not be summed to create a total.
The safety counts do not establish that the death was treatment-related, and they should not be equated with the primary outcome’s dose-limiting toxicities. The primary result separately reports 2 dose-limiting toxicities among 6 participants at the first dose level. Further details on event timing, severity grading, attribution, and overlap are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted primary result documents dose-limiting toxicities at the first dose level and an unresolved dose-selection objective. The registry reports 2 dose-limiting toxicities in 6 treated participants, and explicitly states that the study was terminated before additional dose levels were explored. It reports no maximum tolerated dose and no recommended phase 2 dose. The result is therefore an incomplete dose-finding outcome, not a selected regimen.
The findings describe what was recorded in this small, early-phase study. They do not establish the frequency of toxicity in a broader population, because the enrolled group was small and the record does not provide an uncertainty interval. They also do not show how toxicity would have differed at the other planned dose levels, since those levels were not explored according to the primary outcome description. The listed planned cohorts cannot be treated as observed dose groups.
The record does not support a conclusion about whether the combination improves tumor outcomes. Antitumor effects were a secondary outcome, but numerical results are not reported in the registry record. There is no randomized comparator, and the record reports 0 analyses. Consequently, no comparative treatment effect or inferential conclusion can be drawn from the posted results.
The safety information is descriptive and distinct from the dose-finding outcome. Counts of serious and other adverse events, the listed serious-event terms, and the reported death provide context for events recorded in the safety group. They do not by themselves establish causality, event overlap, or a relation between the death and treatment. These distinctions are important when reading adverse-event listings in any early-phase trial.
Overall, the registry documents a study that began dose evaluation but stopped before its planned dose-selection question was answered. It does not establish a dose recommendation, comparative efficacy, or a complete characterization of safety. Those limits define the scope of what the posted results can mean.
13. Why This Trial Matters Statistically
This trial illustrates a central statistical challenge in early-phase research: a dose-finding study depends on observations across dose levels, yet enrollment and study duration may not allow the planned escalation to be completed. Here, the registry reports 6 participants treated at the first dose level and 2 dose-limiting toxicities, followed by termination before exploration of additional dose levels. The maximum tolerated dose and recommended phase 2 dose were not identified. The result makes the distinction between collecting safety observations and answering a dose-selection question especially clear.
It also shows why a small count should be interpreted descriptively. Counts can be important for detecting and documenting safety events, but a limited number of observations gives little basis for precise estimates of event frequency or for generalization beyond the treated participants. A confidence interval and participant-level details are not reported, so uncertainty and overlap cannot be evaluated from the registry record.
The study also demonstrates why design context matters. A sequential, nonrandomized escalation study is not a randomized comparison, and its dose cohorts should not be read as if they were comparable treatment arms. The primary objective was dose selection, while antitumor effects were secondary. Since numerical results for that secondary outcome are not reported, the record does not answer a comparative efficacy question.
Finally, the distinction between a planned analysis and a posted analysis matters for transparent interpretation. The record describes basic descriptive summaries and protocol-based dose-selection criteria, but the criteria are not reported and no analyses are posted. The result is informative about what was observed at the first dose level and about the fact that dose selection remained incomplete; it cannot support conclusions that require the unreported escalation experience or analysis plan.
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 main trial-specific limitation is that dose escalation stopped before additional dose levels were explored. Although the record lists several planned cohorts with different AR-42 and pazopanib doses, the primary result reports treatment only at the first dose level. The results therefore cannot establish the toxicity profile across the planned dose range or identify a maximum tolerated dose or recommended phase 2 dose.
Enrollment was 6, and the posted result reports 2 dose-limiting toxicities in that group. With this limited enrollment, the observed count offers little precision for estimating toxicity beyond the participants treated. The registry does not report a confidence interval, participant-level event details, or the number meeting the stated evaluability rule.
The record describes the study as terminated but does not report the reason for termination. It also does not report the protocol’s dose-selection criteria, a sample-size justification, interim analysis procedures, or a detailed statistical analysis plan. The precise handling of nonevaluable participants and missing outcomes is not reported in the registry record.
The study was nonrandomized, unmasked, and sequential, so it does not provide a like-for-like control comparison. Numerical results for the listed antitumor-effects outcome are not reported, and the registry reports 0 analyses. Safety listings do not give enough detail to establish event attribution, overlap, or the relation of the death to treatment. These limitations restrict interpretation to the descriptive observations and incomplete dose-finding result recorded in the registry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of the Pan-DAC Inhibitor AR-42 and Pazopanib in Advanced Sarcoma and Kidney Cancer — NCT02795819.
- Registry record last updated 2019-10-24; status last verified 2019-10.
- Results first posted 2019-10-24.
- 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
NCT02795819 was a phase 1, nonrandomized, unmasked, sequential study sponsored by Virginia Commonwealth University. It evaluated oral AR-42 with continuously administered oral pazopanib in advanced soft tissue sarcoma and renal cell carcinoma. The registry reports enrollment of 6, a start date of 2016-07-08, a primary completion date of 2016-11-24, and terminated status.
The primary objective was to identify recommended phase 2 doses using dose-limiting toxicities during the first treatment cycle. The posted result reports 2 dose-limiting toxicities among 6 participants treated at the first dose level. The study ended before additional dose levels were explored; no maximum tolerated dose or recommended phase 2 dose was identified. Antitumor effects and treatment-related adverse events were listed as secondary outcomes, but numerical results for these outcomes are not reported in the registry record. The safety listing includes serious adverse events, other adverse events, and a death, without enough information to establish causality or event overlap.