Dose-Finding and Safety Study for Oral Single-Agent to Treat Advanced Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose-Finding and Safety Study for Oral Single-Agent to Treat Advanced Malignancies (NCT02030067), a na phase 1, phase 2 study. The primary outcome is Overall Safety Profile Characterized by # of Subjects With Dose-limiting Toxicities (DLTs) in Phase 1.

2. Clinical Question

The study asks two related but distinct questions. In Phase 1, its stated purpose was to determine the maximum tolerated dose of RX-3117 in subjects with advanced or metastatic solid tumors. The primary endpoint focuses on the number of Phase 1 participants who experienced a dose-limiting toxicity during the first treatment cycle, defined as 28 days. This is a dose-finding and safety question, not a comparison of RX-3117 with another treatment.

The Phase 2 purpose was to estimate anti-tumor activity in subjects with advanced malignancies, specifically relapsed or refractory pancreatic cancer or advanced bladder cancer. The registry lists best overall response rate as a secondary outcome for Phase 2. It also lists area under the plasma concentration time curve for Phase 1, reflecting the study's pharmacokinetic interest. The posted record does not report results for these outcomes.

The study is listed for solid tumor and metastatic bladder cancer conditions. Its single-group structure means participants received RX-3117 rather than being assigned to a concurrent control arm. The dose-escalation groups involved different schedules and amounts, while the Phase 2 group is listed as 700 mg. These groups address dose and activity questions within the study, but they do not create a randomized comparison with an untreated or active-control group.

The central interpretive question is therefore what the registry record can establish about dose-limiting toxicity and safety, and how far the posted information can address anti-tumor activity. The record identifies the endpoint and reports adverse-event counts for dose groups, but it does not report the primary endpoint result, a maximum tolerated dose determination, or Phase 2 response results. Those omissions limit conclusions about the stated research questions.

3. Trial Design

The registry lists this as a Phase 1 and Phase 2 study. Its official title describes an open-label, dose-ranging, safety and pharmacokinetic study of oral RX-3117 as a single agent in subjects with advanced malignancies. The study is marked completed, with enrollment of 127. The recorded start is 2013-12 and primary completion is 2019-07.

The design is classified as single group, with allocation listed as NA and masking listed as none. All subjects are described as receiving RX-3117. There is no randomized control group in the registry design, so the dose groups should not be read as like-for-like treatment arms. They differ in dose and, in several Phase 1 groups, dosing frequency. Differences among their observed counts could reflect group composition, dose schedule, or chance, and the registry does not provide an adjusted comparative analysis.

Phase 1 is described as dose escalation, with groups ranging from 30 mg 3x/Week through 2000 mg 3x/Week, as well as schedules of 500 mg 5x/Week, 700 mg 5x/Week, and 500 mg 7x/Week. The Phase 2 group is listed as 700 mg. These are the group labels in the safety record; they do not, on their own, establish the dose selected as the maximum tolerated dose or explain the dose-selection procedure.

The Phase 1 primary endpoint counts participants experiencing a dose-limiting toxicity during the first cycle, or 28 days. The Phase 2 objective is to estimate anti-tumor activity in the specified malignancies. The registry does not report the detailed protocol, dose-escalation rules, eligibility criteria, allocation procedures beyond the single-group designation, or a statistical analysis plan. It therefore supports a description of the broad study structure, but not a reconstruction of how decisions were made during conduct.

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: 3 patients enrolled in the Phase 2 portion of the study discontinued prior to dosing. Therefore 124 patients started the study rather than 127 patients as listed in the protocol section.

Only the first 6 of 13 groups are shown.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Overall Safety Profile Characterized by # of Subjects With Dose-limiting Toxicities (DLTs) in Phase 1, measured over 28 days.

The primary endpoint is the number of Phase 1 participants who experienced a dose-limiting toxicity during the first cycle of treatment, defined in the registry as 28 days. It is a participant count. The registry does not post the observed count for this endpoint, nor does it give a corresponding denominator or dose-specific DLT result in the primary outcome entry.

In general, dose-limiting toxicity is used in early dose-finding research to identify toxicities considered important for decisions about dose escalation and dose selection. A defined observation window helps specify when events count toward that endpoint. It does not capture every possible safety outcome over the full study, and it should not be conflated with all adverse events or with serious adverse events. The registry's adverse-event summaries are separate safety information and do not substitute for the endpoint result.

The endpoint is relevant to the stated Phase 1 purpose of determining the maximum tolerated dose. However, the registry record does not report whether a maximum tolerated dose was determined, how a DLT was defined in the protocol, how events were reviewed, or how the DLT count was used to select a dose. Without the endpoint result and those details, the endpoint's intended role can be described, but the dose-finding conclusion cannot be independently evaluated from the posted record.

The listed secondary outcomes include a Phase 1 pharmacokinetic measure, area under the plasma concentration time curve, and Phase 2 best overall response rate. Their results are not reported in the registry record. The endpoint description therefore gives a clear measurement window and type of outcome, but not an estimate of toxicity frequency or treatment activity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as binary and describes it as a count of participants with an event. In general, binary outcomes record whether each participant did or did not experience a defined event within a specified period. A participant count is not itself a risk estimate: interpreting a frequency requires a denominator, and comparing frequencies requires a clearly defined comparison and analysis. The primary endpoint has a 28-day observation window, but its observed count and denominator are not reported in the primary outcome entry.

What does the DLT endpoint represent?

As a general statistical concept, an early dose-finding endpoint condenses a clinically defined toxicity criterion into an event indicator for each participant. The resulting count can inform dose selection when it is interpreted under prespecified escalation rules and with adequate detail about event definitions and assessment. A DLT count is distinct from a count of any adverse event: not every adverse event necessarily meets the protocol definition of a dose-limiting toxicity. The registry record does not report the detailed DLT definition or the decision rules used in this study, so those cannot be reconstructed from the endpoint label.

The Phase 1 endpoint covers the first treatment cycle, or 28 days. A fixed window makes the endpoint's intended time horizon explicit. It does not mean that safety beyond that period is represented by the DLT count. Adverse events may be reported over another observation period or according to other registry conventions; those details are not reported in the registry record. The Phase 1 primary outcome should therefore be interpreted only as the defined early-cycle endpoint, not as a complete accounting of all harms during participation.

Why do the dose groups not form a controlled comparison?

In general, random allocation helps balance measured and unmeasured participant characteristics across treatment groups, supporting a causal comparison. This study is listed as single group, with allocation NA and no masking. Its dose-escalation groups are different exposure groups within a dose-ranging study, not randomized control arms. Participants in different groups may also differ for reasons that the record does not describe. As a result, a difference in observed counts across groups would not by itself establish that dose caused the difference.

Group sizes also vary, and some Phase 1 groups contain very few participants. With small denominators, one participant's outcome can materially change the descriptive pattern. In general, estimates from small groups have substantial sampling uncertainty. Without interval estimates or a model accounting for the design, the posted counts should be read as observations in those groups rather than precise estimates for a broader population.

What can the adverse-event counts tell readers?

The registry separates participants at risk from participants affected for serious and other adverse events. In general, the affected count describes how many participants in a group had at least one qualifying event under the registry's reporting convention; it is not necessarily the number of individual event episodes. The record labels the counts by group and reports deaths separately. It does not provide enough detail in the posted summary to determine event duration, recurrence, timing, relationship to study drug, or the attribution of deaths. A count should not be translated into a causal claim.

The listed serious terms include hypoglycemia at 100.0%, and pneumonia, stomatitis, vomiting, cerebrovascular accident, and pleurisy at 33.3% each. The registry record does not explain the denominators or calculation conventions for those term percentages in the information. They should be understood as listed serious-event terms, not as a complete event profile or as evidence of treatment attribution.

How should statistical significance and precision be understood?

In general, a confidence interval describes the uncertainty around an estimate under a specified statistical method. It can show which effect sizes are reasonably compatible with the data, whereas a point estimate alone does not convey that range. A hypothesis test addresses compatibility with a null hypothesis under its assumptions; it does not measure clinical importance or prove causality. Neither intervals nor tests for the study outcomes are reported in the registry record, and there are no posted analyses. Statistical significance therefore cannot be assessed from the available outcome entries.

For counts or proportions, uncertainty depends in part on the number of participants and events, and interpretation also depends on how the outcome and analysis population were defined. The registry lists enrollment of 127, but does not report endpoint-specific denominators or analysis populations. Enrollment is not necessarily the same as the number evaluated for a particular outcome. No missing-data procedures are reported, so it is not possible to determine how participants without complete endpoint information were handled.

What is the role of the planning illustration?

In general, sample-size planning translates assumptions about an effect, significance level, allocation, and statistical model into a target number of participants or events. A planning illustration based on an observed effect is conditional on that effect estimate and on its assumptions. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers effects expressed as a fraction of the observed effect. Those assumptions do not match the registry's single-group dose-escalation design and should not be mistaken for its documented protocol.

A planning calculation is not an observed power calculation. It cannot show that the trial had a particular probability of detecting an effect after the study has been completed, and it does not replace an analysis of the actual outcomes. The registry does not report the numerical planning results, the original sample-size justification, or the statistical assumptions used in the trial's own design. These details are not reported in the registry record.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("RX-3117 30 mg, 3 Times/Week", "RX-3117 60 mg, 3 Times/Week", "RX-3117 100 mg, 3 Times/Week", "RX-3117 150 mg, 3 Times/Week", "RX-3117 200 mg, 3 Times/Week", "RX-3117 500 mg, 3 Times/Week")
n      <- c(1, 1, 3, 3, 3, 3)
events <- c(0, 0, 0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  RX-3117 30 mg, 3 Times/Week  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  RX-3117 60 mg, 3 Times/Week  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  RX-3117 100 mg, 3 Times/Week  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  RX-3117 150 mg, 3 Times/Week  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  RX-3117 200 mg, 3 Times/Week  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  RX-3117 500 mg, 3 Times/Week  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes: the Phase 1 primary endpoint of participants with dose-limiting toxicities during the first cycle, a Phase 1 area-under-the-curve pharmacokinetic outcome, and Phase 2 best overall response rate, along with a total of 8 outcome measures. The record does not report how these outcomes were prioritized beyond identifying the primary endpoint, how multiple statistical tests were handled, or whether any multiplicity adjustment was planned. No outcome analyses are posted, so there are no reported estimates or tests to evaluate in light of multiplicity.

Multiplicity matters in general when several outcomes, time points, subgroups, or comparisons are tested. Repeated testing can increase the chance of observing apparently notable results by chance if no strategy is specified. This general concern does not mean that a particular result is false; it means that interpretation depends on knowing which analyses were planned and how they were treated. The registry record does not report a detailed statistical analysis plan, interim analyses, or subgroup analysis procedures.

The record also does not report analysis populations for the primary or secondary outcomes. Although enrollment is listed as 127, the numbers evaluated for each outcome are not specified in the outcome descriptions. Missing-data methods, censoring rules, handling of participants who discontinued, and the completeness of outcome ascertainment are not reported in the registry record. Without those details, enrollment cannot be assumed to equal the endpoint analysis denominator.

These gaps limit assessment of both bias and precision. They prevent readers from determining whether analyses followed prespecified rules, whether all enrolled participants contributed to each outcome, or whether exclusions could have changed the results. The registry record does not report these methods, and the absence of posted analyses means there is no statistical result to reconcile with them.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypoglycemia (100.0%), pneumonia (33.3%), stomatitis (33.3%), vomiting (33.3%), cerebrovascular accident (33.3%).

The serious adverse-event figures are participant counts within the listed dose groups. In the Phase 2 700 mg group, 29 of 80 participants are recorded as affected by serious adverse events, and 78 of 80 are recorded as affected by other adverse events. The group also lists 8 deaths. These are separate registry summaries; the other-adverse-event count should not be added to the serious-event count because the record does not establish that the categories are mutually exclusive.

In Phase 1, the serious-event counts vary by dose and schedule. The 60 mg 3x/Week group lists 1 of 1 participant with a serious adverse event; the 100 mg 3x/Week, 150 mg 3x/Week, 200 mg 3x/Week, and 500 mg 3x/Week groups each list 0 affected participants among 3 at risk. Other small groups have different counts, including 2 of 6 at 2000 mg 3x/Week and 5 of 11 at 700 mg 5x/Week. These are descriptive counts, not controlled comparisons.

In general, an adverse-event record does not by itself establish that an event was caused by treatment. The registry information does not report event timing, individual clinical detail, or causal attribution for the figures described. Deaths are listed, but their causes and relationship to RX-3117 are not reported in the registry record. The serious-event term percentages are listed separately and should not be treated as evidence of causality.

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

The record documents a completed study of oral RX-3117 with a Phase 1 dose-ranging and safety purpose and a Phase 2 anti-tumor activity objective. It identifies a primary Phase 1 endpoint with a defined 28-day window and reports adverse-event counts by dose group. Those details help readers understand what the study was intended to examine and what types of safety information were recorded.

The posted information does not report the primary DLT count or the study's maximum tolerated dose determination. It also does not report Phase 2 best overall response results or the Phase 1 pharmacokinetic outcome. The absence of those results means the stated dose-finding, activity, and pharmacokinetic questions cannot be answered from the registry record. A safety count from the adverse-event summary is not a substitute for the primary endpoint or for response data.

The listed serious adverse events and deaths describe events recorded among participants in the dose groups. They do not establish a causal link to RX-3117, and they do not allow comparison with what might have occurred without treatment or under another treatment. The single-group design has no randomized control arm. Dose groups should not be treated as equivalent to randomized arms because they differ in dose and schedule and may differ in other ways not reported in the registry.

General statistical interpretation also depends on precision, outcome definitions, and analysis populations. The registry record does not report confidence intervals, hypothesis tests, missing-data procedures, or detailed analysis methods. Thus, the posted counts cannot establish the precision of any population-level estimate. Nor can a planning illustration be treated as a measure of observed study power.

These limits do not erase the descriptive information: participants were enrolled, received the listed study drug schedules, and adverse-event counts were recorded. They define what conclusions those details can support. The registry record alone does not establish efficacy, treatment-related harm, the optimal dose, or comparative benefit.

14. Why This Trial Matters Statistically

This study illustrates why design labels and endpoint definitions matter when reading early-phase clinical research. A Phase 1 study may use toxicity observations to guide dose decisions, but the usefulness of that evidence depends on knowing the DLT definition, observation window, escalation rules, and actual endpoint results. The registry specifies the first-cycle, 28-day window and participant-count endpoint, yet does not report the observed DLT result or the dose-selection conclusion. The gap between a clearly named endpoint and an unavailable result is statistically important.

The study also shows the distinction between safety summaries and controlled treatment comparisons. A single-group dose-ranging design can describe events recorded at different dose schedules. It cannot, by itself, separate a treatment effect from differences in participant characteristics, exposure, or other factors. The dose-group counts are especially difficult to compare when group sizes differ and are small. Descriptive observations remain useful, but their scope should not be overstated.

Phase 1 and Phase 2 address different questions in this record. Dose-limiting toxicity is the primary Phase 1 endpoint, whereas Phase 2 aims to estimate anti-tumor activity and lists best overall response rate as a secondary outcome. Treating those questions as interchangeable would obscure the design's objectives. The absence of posted response results means that the Phase 2 activity question remains unanswered in the registry record.

Finally, the record highlights the importance of transparent statistical reporting. Without analyses, uncertainty estimates, analysis populations, and missing-data methods, readers cannot evaluate precision or determine how outcomes were handled. Planning assumptions based on two-arm allocation do not describe this single-group design. Clear separation of observed outcomes, design assumptions, and general statistical explanations helps prevent descriptive counts from being read as stronger evidence than they are.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation for interpreting this study record is that the primary endpoint is defined but its result is not reported. The number of Phase 1 participants with a dose-limiting toxicity during the first cycle is unavailable, and the registry record does not state whether a maximum tolerated dose was identified. Without those details, the study's main Phase 1 question cannot be assessed from the posted outcome information.

The Phase 2 activity outcome is also unavailable. Best overall response rate is listed, but no response estimate or analysis is reported. The Phase 1 pharmacokinetic outcome is likewise listed without results. Thus, the registry does not provide the key outcome information needed to evaluate either stated study objective.

The available adverse-event counts are not accompanied by details about event timing, duration, recurrence, attribution, or ascertainment. The listed deaths do not have reported causes or treatment-relatedness in the summarized record. The event-term percentages are not accompanied by denominator explanations. As a result, the safety summaries offer limited descriptive context and cannot establish causal relationships.

The study has no randomized control group, and its dose groups vary in dose, schedule, and size. They do not support an unbiased treatment comparison. The registry record also does not report detailed eligibility criteria, protocol-defined DLT rules, dose-escalation procedures, statistical analysis methods, analysis populations, missing-data handling, or interim analysis procedures. These omissions limit reproducibility and appraisal of potential bias and precision.

Finally, enrollment of 127 does not identify the number of participants analyzed for each outcome. No confidence intervals or statistical tests are posted. Without endpoint-specific denominators and methods, the precision and completeness of outcome estimates cannot be assessed. These are limits of the registry record, not evidence that an unreported result had any particular direction.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dose-Finding and Safety Study for Oral Single-Agent to Treat Advanced Malignancies — NCT02030067.
• Registry record last updated 2023-12-06; status last verified 2023-11.
• Results first posted 2023-12-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, open-label, single-group Phase 1 and Phase 2 study of oral RX-3117 in advanced malignancies, with enrollment of 127. Phase 1 aimed to determine the maximum tolerated dose; Phase 2 aimed to estimate anti-tumor activity in specified advanced malignancies. The primary endpoint was the number of Phase 1 participants with a dose-limiting toxicity during the first treatment cycle, defined as 28 days.

The registry lists Phase 1 area under the plasma concentration time curve and Phase 2 best overall response rate as secondary outcomes. It reports adverse-event counts across dose groups, including serious adverse events, other adverse events, and deaths. However, the primary endpoint result, response results, pharmacokinetic results, and statistical analyses are not reported in the registry record. The single-group design does not provide a randomized control comparison, and the adverse-event counts alone do not establish treatment causation.