Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer (NCT00425386), a na phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib..

2. Clinical Question

The stated purpose was to study the best erlotinib dose when given with sunitinib and to assess treatment in patients with unresectable or metastatic kidney cancer. The primary endpoint is a dose-finding question, rather than a comparison of the combination against another treatment. The registry lists secondary outcomes concerning safety, median time to progression, best overall response categories, and maximum percent change in tumor measurement.

The record does not report the observed maximum tolerated dose, dose-limiting toxicity counts by dose, or results for the secondary outcomes. Consequently, the registry record does not establish which dose was selected or describe the size or precision of any treatment effect.

3. Trial Design

This was a phase II, single-group, dose-escalation study of erlotinib with sunitinib in advanced renal carcinoma. The registry lists an enrollment of 60 and records the study as completed. The start is listed as 2006-08 and primary completion as 2010-08. The sponsor was OHSU Knight Cancer Institute.

The combination arm description gives five erlotinib dose levels: 50 mg/day, 75 mg/day, 100 mg/day, 125 mg/day, and 150 mg/day, each described as continuous daily dosing. Sunitinib was described as 50 mg daily, given 4 weeks on and 2 weeks off. These dose levels are features of escalation, not separate randomized groups. Allocation is recorded as NA, masking as none, and the model as single group; the registry therefore does not describe a blinded or randomized comparison.

The primary endpoint was the maximum tolerated dose of erlotinib hydrochloride with sunitinib. The registry defines MTD by dose-limiting toxicity in 33% of patients. It states that participants were assessed for DLTs weekly during the first treatment cycle and every 3 weeks in subsequent cycles, until at least one DLT occurred in 33% or more of participants at that dose. Assessment was listed for the duration of the study, up to 7 years.

The intervention list includes erlotinib hydrochloride, sunitinib malate, and biopsy. The registry also identifies safety, time to progression, best overall response, and tumor-measurement change as secondary outcomes. Detailed eligibility criteria, dose-escalation rules beyond the endpoint description, treatment-discontinuation rules, and the statistical analysis 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.

Before assignment: The discrepancy between the number of participants enrolled (60) and the number of participants Started in the Participant Flow module (46) is due to screen failures and consent withdrawals.

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.

Population: The discrepancy between the number of participants enrolled (60) and the number of participants Started in the Participant Flow module (46) is due to screen failures and consent withdrawals.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib., measured over Participants assessed for DLTs weekly during the first cycle of treatment and every 3 weeks in subsequent cycles until at least one DLT occurs in 33% or more of participants at that dose; participants assessed for the duration of the study, up to 7 years.

The primary endpoint is the maximum tolerated dose of erlotinib hydrochloride when used with sunitinib. The registry defines the MTD as the dose producing dose-limiting toxicity in 33% of patients. It describes assessments weekly during the first cycle and every 3 weeks in later cycles, continuing until the threshold is reached at a dose. The listed assessment period extends for the duration of the study, up to 7 years.

In general, a dose-finding endpoint such as MTD is used to identify a dose level in a combination regimen with a specified level of treatment-limiting toxicity. It answers a different question from whether a regimen improves an outcome compared with another treatment. Here, the endpoint concerns erlotinib dose in the setting of concurrent sunitinib, so tolerability at a dose cannot be interpreted independently of the combination described in the record.

The registry record does not report the observed MTD, the DLT counts at each dose, or uncertainty around a selected dose. It therefore gives the endpoint definition and assessment schedule, but not the primary endpoint result. The registry’s threshold definition should not be mistaken for evidence that any particular dose did or did not meet it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group phase II dose-escalation design. In general, dose escalation studies evaluate successive dose levels to characterize tolerability and identify a dose that meets a prespecified toxicity criterion. This is different from a randomized trial designed to estimate a contrast between treatment groups. In this study, the stated primary question concerns erlotinib dose with sunitinib, and the registry does not list a separate comparator group.

What does the MTD definition mean?

The registry defines maximum tolerated dose as the dose that produces dose-limiting toxicity in 33% of patients. This percentage is the stated decision target, not a reported observed toxicity rate. The record says participants were assessed for DLTs weekly during the first treatment cycle and every 3 weeks in subsequent cycles until at least one DLT occurred in 33% or more of participants at that dose. It also lists assessment for the duration of the study, up to 7 years. The registry does not provide dose-specific DLT counts, the number assessed at each dose, or the estimated MTD.

In general, a toxicity threshold is useful because it makes the dose-selection objective explicit. However, an estimated dose based on a finite group of participants is subject to uncertainty. A dose whose observed toxicity proportion is near a decision boundary may be difficult to distinguish from a neighboring dose. Confidence intervals can express uncertainty around an estimate; no confidence interval for the primary endpoint is reported in the registry record. The dose-escalation algorithm and its operating characteristics are also not reported, so the exact rule for moving among levels cannot be reconstructed from the endpoint definition alone.

How should the regimen be understood?

The registry lists continuous daily erlotinib levels of 50 mg/day, 75 mg/day, 100 mg/day, 125 mg/day, and 150 mg/day. Sunitinib is described as 50 mg daily, with 4 weeks on and 2 weeks off. The question is therefore about the tolerated erlotinib dose in the context of this sunitinib schedule. The record does not provide exposure measurements, adherence data, dose reductions, or treatment duration by participant. These details matter in general because delivered dose and time exposed can affect observed toxicity, but they cannot be characterized for this study from the registry record.

The primary endpoint is a dose-finding endpoint, while the listed secondary endpoints cover distinct outcomes. Safety concerns adverse events; time to progression concerns time until a defined event; response categories describe best overall response; and maximum percent change concerns tumor measurement. These endpoints need not use the same analysis method or participant set. The registry record does not specify endpoint analysis methods, event definitions beyond the listed labels, censoring rules, or the analysis population for each outcome.

What can sample-size planning illustrations establish?

In general, sample-size calculations estimate how much information a future study would need under stated assumptions. They are planning illustrations, not observed power for a completed study. The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of an observed effect. For time-to-event planning, the stated quantity is total events; other planning quantities are participants per arm. Those assumptions do not change the actual study design, which is recorded as single group, nor do they supply a randomized comparison for this trial.

Because the registry record does not report the observed treatment effect or a primary endpoint result, those assumptions cannot be used to infer a clinically meaningful effect or a study-specific power estimate from the record. Sample-size planning should not be read as evidence that an effect was detected or excluded. No number of participants needed for a particular power target is stated in the registry record described for this analysis.

What do the safety entries convey?

The registry records serious adverse events and other adverse events separately. In general, event counts and the number of participants affected summarize reported safety experience, but they do not by themselves describe exposure-adjusted rates or establish causation. A percentage attached to a serious-event term is not necessarily the percentage of all events, and repeated terms may reflect the registry’s reporting format. The serious-event terms and their percentages are listed without additional event-level detail. The record does not state whether the terms are mutually exclusive or describe the method used to code them.

More broadly, a confidence interval would communicate the range of values compatible with an estimate under a specified statistical procedure, while a p-value would summarize evidence against a null hypothesis under its assumptions. Neither can be interpreted without a defined estimand, analysis method, and result. The registry record does not report p-values or confidence intervals for the primary endpoint, and it does not report the analysis plan needed to infer what model or testing procedure would have been used. No statistical model, adjustment strategy, or interim analysis is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes alongside the primary MTD endpoint: safety, median time to progression, best overall response categories, and maximum percent change in tumor measurement. When a study evaluates multiple outcomes or categories, the chance of at least one apparently notable finding can increase if many statistical tests are conducted. In general, multiplicity procedures can control the overall error rate, or investigators can designate analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which outcome comparisons, if any, were intended to support formal claims.

Missing-data handling is also not reported in the registry record. The record does not describe how participants who discontinued treatment, missed assessments, or lacked evaluable tumor measurements were handled. It does not state how censoring was defined for time to progression, how best overall response was assigned when assessments were incomplete, or how missing DLT assessments were treated. These choices can affect estimates and the population represented by an analysis.

The record lists an enrollment of 60, while the adverse-event group has 46 at risk. It does not explain the relationship between those figures. The numbers should not be assumed to identify the same analysis population, and the registry does not state the number evaluated for the primary endpoint or for each secondary outcome. Analysis-population definitions—such as who was included in a safety or efficacy analysis—are not reported in the registry record.

Because the study is recorded as single group, there is no randomized control comparison from which to estimate a between-group contrast. The record also does not report the statistical analysis plan, interim analyses, or methods for handling multiple dose levels. These omissions limit interpretation of the precision and decision process behind any potential result; the primary endpoint result itself is not reported in the registry record.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hematuria (2.2%), disease progression (2.2%), spontaneous pneumothorax (2.2%), carcinoma of prostatic urethra (2.2%), angioedema (2.2%).

The registry records a Sunitinib and Erlotinib group with 46 at risk for serious adverse events and 7 affected. For other adverse events, it records 46 at risk and 46 affected. These are separate registry entries and should be read within their respective categories. The record does not state whether the same participants appear in both categories, and the figures should not be added to create a total.

The serious-event terms listed are hematuria, disease progression, spontaneous pneumothorax, carcinoma of prostatic urethra, angioedema, and hypomagnesemia. Each term is paired with 2.2%. The registry does not provide further detail about event timing, severity grade, duration, recurrence, or whether an event was judged related to treatment. The percentages alone do not describe the full distribution of serious events or the risk over time.

In general, adverse-event entries describe reported events in the recorded study population; they do not establish that a treatment caused an event. Since this study is recorded as single group, the safety figures do not provide a like-for-like comparison with another treatment. The registry does not report deaths in the adverse-event entry.

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

The registry record establishes that a phase II single-group dose-escalation study examined erlotinib with sunitinib in patients described as having unresectable or metastatic kidney cancer. It records five erlotinib daily dose levels and a sunitinib schedule of 50 mg daily, 4 weeks on and 2 weeks off. It defines the primary endpoint as MTD, using dose-limiting toxicity in 33% of patients as the criterion.

What the record does not establish is the observed MTD, the dose-specific DLT experience, or the outcome of the study’s secondary endpoints. The primary endpoint result is not reported in the registry record. The record therefore cannot show which erlotinib dose was selected or how precisely that dose was determined. The stated objective and endpoint definition should not be mistaken for a reported finding.

The safety entries describe 7 affected by serious adverse events among 46 at risk and 46 affected by other adverse events among 46 at risk. The listed serious-event terms each carry a percentage of 2.2%. Those entries provide limited descriptive safety information; they do not establish causation, comparative safety, or the frequency of events over a specified exposure period. No separate randomized comparator is recorded.

In general, a single-group dose-finding study can address tolerability and dose selection within its regimen, but it cannot by itself determine how outcomes compare with an alternative treatment. The registry’s secondary outcomes include time to progression, best overall response, and tumor-measurement change, but results for those outcomes are not reported in the registry record. Nor are analysis populations, missing-data procedures, or the statistical analysis plan reported. The available record supports a description of the research question and design, not a conclusion about clinical benefit or lack of benefit.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary question is about dose selection, not a treatment-versus-control effect. The distinction matters: a maximum tolerated dose is defined through toxicity experience at dose levels, whereas an efficacy comparison requires an explicit contrast between groups. The registry records a single-group design and no separate comparator, so the study structure should not be interpreted as a randomized comparison.

The endpoint definition also makes the decision target clear: the MTD is the dose producing DLT in 33% of patients. In general, setting a toxicity threshold gives a dose-finding study a practical statistical objective. Yet the observed dose-specific data and uncertainty are essential for evaluating the result. The registry record does not report the MTD or DLT counts by dose, so the dose-selection outcome cannot be assessed from the record.

The entry illustrates why registry design information and reported results are different kinds of evidence. A completed status, a stated aim, and a prespecified endpoint do not supply an estimate. The registry also names secondary outcomes that address different aspects of safety and tumor response, but results for them are not reported in the registry record.

Finally, the safety entries must be interpreted in context. They give affected-participant counts and percentages for listed serious-event terms, but there is no randomized comparison and no event-level detail in the record. This distinction between descriptive counts, a dose-finding decision, and a comparative treatment effect is central to reading the study statistically without claiming more than the record supports.

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 registry record does not report the primary endpoint result, including the selected MTD or dose-specific DLT counts. This is the main limitation for interpreting the central dose-finding question. The record gives the MTD definition and assessment schedule, but not the information needed to evaluate the dose-selection decision or its uncertainty.

The study is recorded as single group, with allocation listed as NA and masking as none. No separate comparator is described, limiting what can be inferred about comparative outcomes. The record also does not report an analysis plan, escalation algorithm details, dose-specific participant counts, confidence intervals, or p-values. Interim analyses are not reported in the registry record.

The listed enrollment is 60, while safety reporting uses 46 at risk. The registry does not explain the relationship between these figures or give analysis-population definitions for the primary and secondary outcomes. Missing-data handling, treatment exposure, adherence, dose modifications, and censoring rules are not reported. These gaps prevent assessment of how the analyzed observations relate to enrollment or how incomplete follow-up may have affected outcome estimates.

Although the record lists secondary outcomes, it does not report their results or describe procedures for multiple outcomes. The safety entries also lack event-level detail and a comparison group. These limitations apply to what can be concluded from the registry record and do not establish that the underlying study lacked additional analyses or information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer — NCT00425386.
• Registry record last updated 2017-05-03; status last verified 2017-05.
• Results first posted 2012-02-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed phase II, single-group dose-escalation study of erlotinib with sunitinib for advanced kidney cancer. Enrollment is listed as 60. Erlotinib was studied at daily dose levels from 50 mg/day to 150 mg/day; sunitinib was described as 50 mg daily, 4 weeks on and 2 weeks off.

The primary endpoint was maximum tolerated dose, defined by dose-limiting toxicity in 33% of patients. The record lists safety and tumor-related secondary outcomes. It does not report the observed MTD or results for those secondary outcomes. Safety entries record 7 affected by serious adverse events and 46 affected by other adverse events, each among 46 at risk; six serious-event terms are listed at 2.2% each. No randomized comparator is recorded, and the statistical analysis plan and analysis populations are not reported in the registry record.