Study of Pazopanib and Ixabepilone in Patients With Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Pazopanib and Ixabepilone in Patients With Solid Tumors (NCT01012362), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Experienced a Dose Limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

This was a Phase I, non-randomized, unmasked, sequential study of pazopanib and ixabepilone in people with solid tumors. The registry record gives an enrollment of 31 and lists a start of 2009-12 and primary completion of 2013-02. Its current status is terminated. The reason for termination is not reported in the registry record.

The treatment description states that pazopanib was taken daily and ixabepilone was administered on day 1 of a 3 week treatment course. The arm descriptions identify an optimum tolerated dose determination component and an optimum tolerated dose confirmation component. Dose Level 1 is described as 400 milligrams of pazopanib with ixabepilone 32 mg/m2; Dose Level 2 as 400 milligrams with 40 mg/m2; and Dose Level 3 as 600 milligrams with 32 mg/m2. The Dose Level 4 description is truncated in the registry record, so its full regimen is not available. The confirmation description specifies Dose Level 3 as 600 milligrams of pazopanib and 32 mg/m2 of ixabepilone.

The record states that 6 participants were included at Dose Level 1 to confirm safety after escalation to Dose Level 2, and that they are grouped with the original 3 participants enrolled at Dose Level 1. This grouping matters when reading dose-level summaries: the recorded groups reflect the registry’s presentation, not randomized treatment assignment. A formal sample-size justification, stopping rules, dose-escalation algorithm, and detailed statistical plan are 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.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced a Dose Limiting Toxicity (DLT), measured over Week 3 of each dose.

The primary endpoint is the number of participants who experienced a dose-limiting toxicity, with assessment during week 3 of each dose. A dose-limiting toxicity, or DLT, is a protocol-defined safety event used in early-phase dose-escalation research. In general, such an endpoint helps investigators judge whether treatment-related toxicities at a dose are sufficiently severe to limit further escalation or require additional evaluation. It is not, by itself, a measure of antitumor benefit.

For this study, a DLT was defined by events during cycle 1: treatment-related hematologic toxicity of grade 4 or greater lasting more than 7 days; treatment-related clinical non-hematologic toxicity of grade 3 or greater, with stated exceptions for nausea, vomiting, or diarrhea without maximal medical intervention and/or prophylaxis; or a delay of more than 2 weeks in starting cycle 2 because of incomplete hematologic recovery or unresolved treatment-related non-hematologic toxicity of grade 3 or greater. The record specifies recovery thresholds for absolute neutrophil count and platelets. Adverse events were classified using Common Terminology Criteria for Adverse Events V 3.0.

The registry record gives the endpoint definition and timeframe but does not report the number of participants with DLTs at each dose. It therefore does not establish, in the reported results, how often the primary endpoint occurred or which dose level met a specified tolerability criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods need to be interpreted in light of the study’s Phase I purpose and sequential, non-randomized design. The registry record describes a dose-escalation study and a primary safety endpoint, but does not report a detailed statistical analysis plan. The explanations below distinguish general statistical concepts from methods actually documented in the record.

What does a DLT count represent?

The primary endpoint is a count of participants who experienced at least one protocol-defined DLT within the stated assessment period. General explanation: a count retains an intuitive link to the number of affected participants, while a rate or proportion also requires a clearly defined denominator and assessment window. In this record, the timeframe is week 3 of each dose, and the DLT definition refers to events during cycle 1. The endpoint results themselves are not reported in the registry record, so no observed DLT count or rate can be interpreted.

DLT definitions are study-specific operational rules. Here, the definition uses toxicity grade, duration, treatment attribution, recovery, and treatment delay. Such criteria make the endpoint more structured than an unrestricted report of any adverse event, but the DLT count remains dependent on the definition and assessment process. The registry record says adverse events were classified according to Common Terminology Criteria for Adverse Events V 3.0. It does not report details of independent review, adjudication, or how borderline cases were handled.

Why does sequential escalation matter?

In a sequential dose-escalation design, dose levels are evaluated in an ordered process rather than assigned at random. General explanation: the sequence can be useful for early safety exploration, but it does not create the balance that randomization is designed to achieve. Participant characteristics, time in the study, and the decisions that govern escalation may differ across levels. Therefore, dose-level counts are mainly descriptive unless a suitable design and analysis support stronger comparisons.

The registry record identifies four dose levels in the adverse-event summary and describes the first three regimens. It states that participants brought back at Dose Level 1 for safety confirmation are grouped with the original Dose Level 1 participants. This grouping should be kept in mind when reading summaries by dose. The record does not report the allocation algorithm, rules for escalation or de-escalation, or the rationale for the confirmation group.

What can adverse-event counts show?

Counts of affected participants describe how many people in a recorded group had an event in the stated adverse-event category. They do not, alone, explain event severity, duration, recurrence, relatedness, or timing. The adverse-event record distinguishes serious adverse events from other adverse events and gives participants at risk and affected for each dose level. The record does not provide enough detail in the registry record to interpret those fields as rates over a common exposure period. Nor should serious adverse events be used as a proxy for the primary DLT endpoint: the outcome definitions differ.

General explanation: when event counts are small, estimates can be imprecise, and a small change in the count can materially affect an estimated frequency. Confidence intervals are one way to communicate that uncertainty. No confidence intervals or inferential analysis for these adverse-event summaries are reported in the registry record. A formal comparison across the non-randomized dose levels would also need to address the design and potential differences between groups, not simply compare raw counts.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the target effect is a specified fraction of the observed effect. For time-to-event outcomes, the stated convention is to give the total number of events; for other outcomes, it is to give participants per arm. General explanation: such calculations estimate the amount of information a hypothetical future comparison might need under the chosen assumptions. They are planning illustrations, not observed power, and they do not show that the current study was designed or powered for a randomized comparison.

That illustration is particularly distinct from this trial’s design: this study is described as non-randomized and sequential, whereas the stated planning assumptions use equal allocation between two arms. The record does not report the numerical illustration results in the registry record, and none should be inferred from the assumptions alone. A protocol-based sample-size justification for the Phase I dose-escalation study is not reported in the registry record.

What analyses are documented?

The registry record lists three outcome measures and zero analyses. The primary endpoint is named and defined, but no primary result count, estimate, hypothesis test, or confidence interval is reported in the registry record. The registry record also does not describe covariate adjustment, interim analyses, handling of repeated assessments, or a prespecified statistical model. General explanation: an analysis plan ordinarily clarifies which participants contribute to each endpoint, how missing observations are handled, and what comparisons or estimates are intended. Without such details, the descriptive safety counts should be read narrowly and the missing primary result should not be reconstructed from other outcomes.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Arm 1: Dose Level 1", "Arm 1: Dose Level 2", "Arm 1: Dose Level 3", "Arm 1: Dose Level 4", "Arm 2: Dose Level 3")
n      <- c(9, 6, 3, 4, 9)
events <- c(0, 3, 0, 1, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Arm 1: Dose Level 1  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Arm 1: Dose Level 2  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Arm 1: Dose Level 3  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Arm 1: Dose Level 4  4  1  25.0  0.6  80.6  4.6  69.9  5.3  71.6
ARM  Arm 2: Dose Level 3  9  2  22.2  2.8  60.0  6.3  54.7  6.7  55.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, including a secondary outcome for the number of participants with treatment-related adverse events. It does not report a multiplicity adjustment, a hierarchy of outcomes, or a strategy for controlling the chance of false-positive findings across multiple statistical tests. Because the record reports zero analyses in the registry entries, no testing approach or adjusted result is documented. General explanation: when several outcomes or comparisons are tested, multiplicity methods can help control the overall risk of misleading positive findings. Whether such methods are needed depends on the analysis goals and design; no approach is reported.

Missing-data methods are not reported in the registry record. The record does not state how participants who stopped treatment, missed an assessment, or lacked an evaluable toxicity assessment were handled for the primary endpoint. It also does not report an analysis population definition, such as which enrolled participants were considered evaluable for DLTs. These omissions matter because the endpoint is based on toxicity observed within a defined treatment period; incomplete follow-up could affect what can be established about a participant’s DLT status.

The registry record notes that participants included for Dose Level 1 safety confirmation are grouped with the original Dose Level 1 participants. It does not specify separate analysis populations for escalation and confirmation or describe how the groups contributed to the primary analysis. No interim analysis plan, missing-data sensitivity analysis, or multiplicity procedure is reported in the registry record. The available information therefore supports a description of the recorded groups and endpoint definition, but not reconstruction of an unreported analysis strategy.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection (25.0%), fatigue (25.0%), decreased platelets (25.0%), atrial fibrillation (25.0%), obstruction of airway (25.0%).

The serious adverse-event summary reports participants at risk and affected within each recorded dose level. At Dose Level 1, 9 participants were at risk and 4 were affected; at Dose Level 2, the figures are 6 and 3; at Dose Level 3, 12 and 7; and at Dose Level 4, 4 and 3. These are descriptive counts. Because allocation was non-randomized and sequential, they are not results from a like-for-like randomized safety comparison.

The record also gives the terms Infection, Fatigue, Decreased Platelets, Atrial fibrillation, Obstruction of Airway, and Respiratory Failure, each with a listed value of 25.0%. The registry record does not report the denominator or further event-level detail for these term percentages. They should not be interpreted as percentages for each dose level or as a complete account of event frequency or severity.

Serious adverse events are not equivalent to the primary endpoint, which is a protocol-defined DLT assessed during week 3 of each dose. The record does not report deaths in the adverse-event summary. Counts alone do not establish causality, comparative risk, or the reason the trial was terminated.

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

The registry record documents an early-phase investigation of pazopanib with ixabepilone across sequential dose levels in people with solid tumors. It gives the study’s primary safety endpoint, its DLT definition, and descriptive serious adverse-event counts. Those details make the intended safety question understandable, but they do not supply the primary endpoint results needed to evaluate how many participants experienced a DLT at each dose.

The record does not report a dose level as an optimum tolerated dose or provide the results of the confirmation component. Although the arm descriptions name an optimum tolerated dose determination and an optimum tolerated dose confirmation, those labels are not themselves evidence that a particular dose was selected or confirmed. The full Dose Level 4 regimen is not available in the registry record because its description is truncated.

The serious adverse-event counts show that affected participants were recorded in each listed dose group. They cannot, without more information, establish a causal effect of either drug, rank doses by safety, or support a randomized comparison. Serious adverse-event terms with a value of 25.0% are also difficult to interpret without their denominators and event-level context. The secondary outcome is named, but its result is not reported in the registry record.

General interpretation: a Phase I dose-escalation study primarily addresses early safety and dose selection questions, rather than providing a definitive estimate of treatment benefit. The registry record does not report efficacy results, and no conclusion about tumor response or clinical benefit follows from the endpoint information. The terminated status likewise does not explain why the study ended. The reason is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between defining an endpoint and reporting its result. The registry record gives a detailed, operational DLT definition, including toxicity grade, duration, treatment attribution, and treatment delay. That definition indicates what the investigators intended to count as a dose-limiting event. However, the primary endpoint counts themselves are not reported in the registry record. A precise definition cannot substitute for outcome data.

It also highlights why study design shapes interpretation. Sequential dose escalation is suited to structured early-phase exploration, but non-randomized groups do not provide the balance of a randomized comparison. The dose-level adverse-event counts can describe what was recorded in the registry, yet they do not isolate a causal dose effect. The stated grouping of Dose Level 1 confirmation participants with the original group is another practical detail that affects how a dose-level summary should be read.

Finally, the record shows how incomplete reporting constrains statistical conclusions. No primary endpoint analysis, confidence interval, missing-data method, or multiplicity strategy is reported in the registry entries. The sample-size assumptions described in the record concern a planning illustration for a hypothetical two-arm comparison, not evidence about the precision or power of this Phase I study. Keeping these distinctions clear prevents descriptive safety counts from being mistaken for a comparative treatment result.

15. Limitations

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

Several trial-specific limitations follow from the registry information. The study was non-randomized and sequential, so comparisons across dose levels are not randomized contrasts. The record does not report participant characteristics by dose level, the escalation rules, or a statistical adjustment intended to address differences between groups. The Dose Level 1 confirmation participants are grouped with the original Dose Level 1 participants, and separate results for those groups are not reported.

The primary DLT outcome is defined but its counts are not reported in the registry record. This prevents assessment of the primary safety endpoint and prevents examination of uncertainty around any dose-level estimate. The record names a confirmation component but does not report its results or identify an optimum tolerated dose. The Dose Level 4 regimen is truncated, which limits interpretation of that group’s treatment exposure.

Further limitations include the absence of reported analysis populations, missing-data handling, inferential methods, and a detailed statistical plan. Serious adverse-event term percentages are listed without denominators in the registry record, and event-level timing and details are not reported. The reason for termination is not reported. These gaps restrict conclusions to the study design and descriptive safety information that the registry record explicitly provides.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Pazopanib and Ixabepilone in Patients With Solid Tumors — NCT01012362.
• Registry record last updated 2017-12-28; status last verified 2017-12.
• Results first posted 2017-06-26.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This is a Phase I, non-randomized, unmasked, sequential study of daily pazopanib with ixabepilone administered on day 1 of a 3 week treatment course in people with solid tumors. The registry record reports enrollment of 31, a start of 2009-12, primary completion in 2013-02, and terminated status.

The primary endpoint is the number of participants who experienced a DLT during the specified assessment period. The registry record defines DLT but does not report its outcome counts or a statistical analysis. Descriptive serious adverse-event counts are reported by dose level, but they are not randomized comparisons and are distinct from the primary endpoint. The record does not report the reason for termination, a selected optimum tolerated dose, or the confirmation results.