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 Phase I/II Trial of Letrozole and Sorafenib in Post-Menopausal Hormone-Receptor + Breast Cancer (NCT00634634), a na phase 1, phase 2 study. The primary outcome is Sorafenib in Combination With Fixed Dose of of 2.5mg of Letrozole Maximum Tolerated Dose (MTD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00634634 |
| Phase | Phase 1, Phase 2 |
| Condition | Metastatic Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 52 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Rutgers, The State University of New Jersey |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned postmenopausal women with hormone-receptor-positive locally advanced or metastatic breast cancer. The registry also lists metastatic breast cancer as a condition. The record describes a total enrollment of 52, but the registry entries do not give a fuller account of eligibility criteria or participant characteristics.
Intervention
Participants received sorafenib in combination with letrozole. The primary outcome description specifies a fixed letrozole dose of 2.5mg. The Phase I portion is described as sorafenib dose escalation, while the Phase II arm is described as sorafenib at the maximum tolerated dose with letrozole. The registry lists sorafenib and letrozole as drug interventions.
Comparator
There is no separate control group in the registry design. Allocation is listed as NA, masking as none, and the model as single group. Dose-level cohorts appear in the adverse-event record, but these are not a randomized, like-for-like comparison and should not be treated as a control arm.
Primary question
The primary question was what sorafenib dose, when combined with letrozole, met the registry’s definition of maximum tolerated dose: the highest dose that does not cause unacceptable side effects. The primary outcome is described over twenty eight days. Although the record names this endpoint, it does not report the resulting maximum tolerated dose. The study also lists clinical benefit rate, median progression-free survival, and overall survival among its secondary outcomes, but numerical results for those outcomes are not included in the registry record for this analysis.
3. Trial Design
The registry describes a Phase I/II, single-group trial of sorafenib and letrozole. Its stated enrollment is 52, and its status is completed. The listed start date is 2008-08-11 and the primary completion date is 2019-04-20. The sponsor is Rutgers, The State University of New Jersey. These administrative details describe the record; they do not establish how long an individual participant was followed.
The study has a dose-escalation component and a Phase II arm. The Phase I adverse-event group descriptions identify sorafenib dose levels -1, 0, and 1 alongside letrozole 2.5mg. The Phase II arm is described as sorafenib at the MTD, with the dose written as 400mg 2x a Day, plus letrozole 2.5 mg daily. The primary outcome title also refers to a fixed letrozole dose of 2.5mg and a sorafenib maximum tolerated dose.
This is not a randomized comparison. The registry lists allocation as NA, masking as none, and the model as single group. Consequently, the dose-level groups should be understood as parts of the trial’s treatment and dose-finding structure, not as comparable randomized treatment and control groups. Differences between their posted safety counts could reflect differences in dose, cohort size, stage of the study, or other features not detailed in the record.
The registry says Phase II added 39 participants. It does not report further details of the recruitment process, the dose-escalation decision rules, or the criteria used to move from Phase I to Phase II. Those details, along with a fuller protocol description, are not reported in the registry record. The absence of those details limits how far the study design can be reconstructed from the posted information alone.
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
| Stage | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily |
|---|---|---|---|---|
| STARTED | 1 | 3 | 9 | 39 |
| COMPLETED | 1 | 3 | 9 | 39 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The primary outcome is the maximum tolerated dose, which is the highest dose of the drug that does not cause unacceptable side effects. The maximum tolerated dose was only analyzed. Then phase 2 added 39 participates.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 1 | 3 | 9 | 39 | 52 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 4 | 36 | 40 |
| Age, Categorical: >=65 years | Participants | 1 | 3 | 5 | 3 | 12 |
| Sex: Female, Male: Female | Participants | 1 | 3 | 9 | 39 | 52 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 4 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 10 | 10 |
| Race (NIH/OMB): White | Participants | 1 | 3 | 9 | 25 | 38 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 1 | 3 | 9 | 39 | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Sorafenib in Combination With Fixed Dose of of 2.5mg of Letrozole Maximum Tolerated Dose (MTD), measured over twenty eight days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | milligrams twice daily |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is maximum tolerated dose (MTD) for sorafenib combined with a fixed dose of letrozole. The registry defines MTD as the highest dose that does not cause unacceptable side effects. The stated timeframe is twenty eight days. This is a dose-finding endpoint: it is intended to identify a dose boundary based on tolerability, rather than directly quantify tumor response or compare survival between treatment groups.
As a general statistical concept, dose-finding endpoints are useful when the safety profile of a treatment combination is still being characterized. They help describe the dose selected for further study under the decision rules used in a trial. The result depends on how unacceptable side effects are defined, when they are assessed, and how the dose-escalation decisions are made. Those operational details are not reported in the registry record, so the endpoint definition cannot be expanded beyond the description posted there.
The record names the MTD as its primary outcome but does not state the dose found to meet that definition. It also does not give a numerical estimate or uncertainty interval for the primary endpoint. The Phase II arm description refers to sorafenib at MTD, but that description is not itself a reported primary outcome result. No numerical efficacy outcome should be inferred from the MTD endpoint or from the choice of dose in the Phase II arm.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record identifies a dose-finding objective but does not provide its numerical result. The primary outcome is MTD for sorafenib combined with a fixed dose of letrozole, assessed over twenty eight days. Although the Phase II arm description refers to sorafenib at MTD, the actual MTD result is not reported in the registry record. A stated arm dose should not be substituted for a reported endpoint result.
The record lists secondary outcomes for clinical benefit rate using RECIST Version 1.1, median progression-free survival, and overall survival assessed as mean months. Their names indicate the outcomes the study was intended to evaluate, but no numerical findings for them appear in the registry record. There are no reported response counts, time-to-event estimates, confidence intervals, or statistical test results to interpret. The record also lists four outcome measures and zero analyses; the outcome-measure count does not provide the missing results.
The design affects what can be concluded from any observed values. This is a single-group study with no masking and no randomized control group. The dose cohorts are not like-for-like controls. Therefore, posted outcomes from the treated participants could describe experience within the study, but they cannot by themselves establish what would have occurred under a different treatment or no treatment. This is especially important for outcomes affected by disease course and participant characteristics.
The safety record lists serious adverse events by dose cohort, along with other adverse events and deaths. These are counts within the registry’s group summaries. The serious adverse event counts are not measures of the probability that an event was caused by either drug. The record does not provide attribution, event timing, exposure-adjusted rates, or a complete account of how events were collected. The listed safety figures should therefore be read as reported summaries, not as causal estimates.
For statistical precision, the record does not supply confidence intervals or other uncertainty measures for the primary endpoint or the secondary outcomes. Without them, it is not possible to judge the precision of an efficacy estimate from this information. Nor is there a reported test of a prespecified treatment contrast. Because the registry design is single group, a comparative treatment effect is not established by the study structure.
The appropriate reading is consequently narrow: this was a completed Phase I/II study designed to examine dose and tolerability, with additional listed clinical outcomes, but the numerical primary and efficacy results are not reported in the registry record. The safety summaries provide descriptive counts with important interpretive limits. Neither the trial’s completion status nor its planned outcomes supplies evidence of a particular clinical benefit or lack of benefit.
9. Statistical Methods Explained
Several statistical ideas help clarify what this record can and cannot establish. The explanations below are general; they do not imply that the trial used a particular analysis method unless that method is explicitly described in the registry record.
What does a single-group design tell us?
A single-group design describes outcomes among participants receiving the study treatment, without a concurrent randomized control group. It can support descriptive reporting and, in dose-finding work, guide selection of a dose according to the study’s safety rules. It does not directly estimate the difference between treatment and control. If an outcome changes over time, the single-group result alone cannot separate treatment effects from other explanations, such as the natural course of disease or differences among participants.
In this record, allocation is listed as NA, masking as none, and the model as single group. Those details mean the listed dose cohorts should not be treated as randomized comparison groups. Comparing their crude event counts would not make them equivalent to a trial contrast. The registry does not report an adjusted comparison between cohorts or a causal analysis.
How should a maximum tolerated dose be understood?
MTD is a dose-selection endpoint, defined in the record as the highest dose that does not cause unacceptable side effects. In general, the result of a dose-escalation study depends on its toxicity definitions, observation period, cohort rules, and decision process. These specify what counts as an unacceptable side effect and how observed events affect subsequent dosing. The primary outcome timeframe is listed as twenty eight days, but further operational details and the escalation rules are not reported in the registry record.
A reported MTD would summarize the outcome of those rules; it would not mean that every participant had the same experience or that the selected dose was free of adverse events. Here, the registry names the MTD endpoint but does not report its result. The Phase II description’s reference to sorafenib at MTD does not provide the missing endpoint analysis or its precision.
What does a confidence interval add?
As a general concept, a confidence interval communicates uncertainty around an estimate. A narrow interval indicates greater statistical precision than a wide interval, subject to the assumptions of the analysis. An interval also helps readers assess which values remain compatible with the data and method. It is not a guarantee that the true value falls inside the particular interval, and it does not correct bias arising from a weak design or incomplete data.
The registry information does not report confidence intervals for the primary outcome or the listed efficacy outcomes. As a result, their precision cannot be assessed from these registry entries. The absence of an interval is not evidence that an estimate is precise or imprecise; it means the uncertainty is not quantified in the record.
Why do denominators and event definitions matter?
Adverse event counts require context. A count among participants at risk is different from an event rate that accounts for how long participants were observed, and neither alone shows whether an event was attributed to treatment. General interpretation also depends on how an event was defined, whether repeated events were counted, and whether all participants had comparable observation. The registry provides at-risk and affected counts for adverse-event categories and dose cohorts, but does not provide enough detail to reconstruct those elements.
Over-dispersion is a general issue for count data: observed counts can vary more than a simple statistical model assumes. If a model ignores that variation, its uncertainty estimates may be too optimistic. This is a general consideration, not a claim about an analysis conducted in this trial. No statistical model for the adverse-event counts is reported in the registry record.
What do the planning illustrations represent?
The stated planning assumptions describe illustrative calculations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated target effect is a fraction of the observed effect. Such calculations are planning illustrations, not observed trial outcomes and not observed power. For time-to-event outcomes, the described calculations use total events; for other outcomes, they express participants per arm. Those assumptions do not create a control group in this single-group trial, and they should not be read as the trial’s own design justification.
The record does not report a sample-size justification or a statistical analysis plan. It also does not give a numerical observed effect in the registry record for this analysis. Therefore, the planning assumptions alone do not permit a reader to verify the underlying calculations or connect them to an efficacy estimate. The registry’s outcome and design details remain the basis for interpreting the study, rather than any unreported analysis method.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and several secondary outcomes, including clinical benefit rate using RECIST Version 1.1, median progression-free survival, and overall survival assessed as mean months. It does not report how statistical testing across these outcomes was handled. In particular, adjustment for multiple comparisons, a hierarchy of confirmatory tests, or a prespecified strategy for interpreting several outcome tests is not reported in the registry record.
As a general statistical issue, examining multiple outcomes can increase the chance of finding an apparently noteworthy result by chance if each is tested independently without an appropriate interpretation plan. This does not mean that a particular finding in this trial is false; it means readers need to know the analysis strategy to judge how much weight to place on multiple results. No numerical efficacy tests are included in the registry record, so there is no reported multiplicity-adjusted or unadjusted finding to assess.
Missing-data handling is also not described. The registry record does not specify how participants with incomplete follow-up, unevaluable outcomes, or missing measurements were handled. The analysis populations are not reported, including whether outcomes were analyzed among all enrolled participants or a defined subset. These details matter because exclusions and incomplete observation can affect both estimates and their uncertainty.
The record gives enrollment and states that Phase II added 39 participants, but those details do not establish the denominator for each outcome analysis. The registry lists four outcome measures and zero analyses; neither count supplies participant-level completeness or analysis-population definitions. Without those details, the extent and potential consequences of missing data cannot be assessed from the registry record.
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 |
|---|---|---|---|
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | 0 | 1 | 0.0% |
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | 1 | 3 | 33.3% |
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | 0 | 9 | 0.0% |
| Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily | 3 | 39 | 7.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | 1 of 1 |
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | 2 of 3 |
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | 7 of 9 |
| Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily | 24 of 39 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | 1 of 1 |
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | 3 of 3 |
| Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | 9 of 9 |
| Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily | 39 of 39 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily |
|---|---|---|---|---|---|
| Hypertension | Cardiac disorders | 0 of 1 | 1 of 3 | 0 of 9 | 1 of 39 |
| Dizziness | Nervous system disorders | 0 of 1 | 1 of 3 | 0 of 9 | 1 of 39 |
| Vomiting | Gastrointestinal disorders | 0 of 1 | 1 of 3 | 0 of 9 | 0 of 39 |
| Infection | Infections and infestations | 0 of 1 | 1 of 3 | 0 of 9 | 0 of 39 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 0 of 1 | 0 of 3 | 0 of 9 | 1 of 39 |
| Hepatobiliary | Hepatobiliary disorders | 0 of 1 | 0 of 3 | 0 of 9 | 1 of 39 |
| Pain - Headaches | General disorders | 0 of 1 | 1 of 3 | 0 of 9 | 0 of 39 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level -1 | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg Daily Dose Level 0:Sorafenib 400mg 1X Daily | Phase l Sorafenib Dose Escalation and Letrozole 2.5mg po Daily Dose Level 1: Sorafenib 400mg 2X Day | Phase II Arm - Sorafenib at MTD (400mg) 2x a Day + Letrozole 2.5 mg po Daily |
|---|---|---|---|---|---|
| Dermatology/Skin | Skin and subcutaneous tissue disorders | 1 of 1 | 0 of 3 | 7 of 9 | 28 of 39 |
| Pain | General disorders | 0 of 1 | 0 of 3 | 4 of 9 | 23 of 39 |
| Gastrointestinal | Gastrointestinal disorders | 0 of 1 | 1 of 3 | 3 of 9 | 19 of 39 |
| Hypertension | Cardiac disorders | 0 of 1 | 0 of 3 | 4 of 9 | 19 of 39 |
| General | General disorders | 0 of 1 | 0 of 3 | 3 of 9 | 19 of 39 |
| constitutional Symptoms | General disorders | 0 of 1 | 0 of 3 | 4 of 9 | 15 of 39 |
| Cardiac | Cardiac disorders | 0 of 1 | 1 of 3 | 2 of 9 | 15 of 39 |
| Infection | Infections and infestations | 0 of 1 | 1 of 3 | 4 of 9 | 11 of 39 |
| Metabolic | General disorders | 0 of 1 | 0 of 3 | 3 of 9 | 12 of 39 |
| Blood | Blood and lymphatic system disorders | 0 of 1 | 1 of 3 | 1 of 9 | 4 of 39 |
Serious events with the highest arm-level rate: hypertension (33.3%), vomiting (33.3%), infection (33.3%), dizziness (33.3%), pain - headaches (33.3%).
The registry lists serious adverse events by dose cohort. The group summaries report participants at risk and participants affected: the Phase I dose level -1 group has 1 at risk and 0 affected; dose level 0 has 3 at risk and 1 affected; dose level 1 has 9 at risk and 0 affected; and the Phase II arm has 39 at risk and 3 affected. These are descriptive group counts, not comparative risk estimates.
The record separately reports other adverse events, with all participants at risk listed as affected in each group. It also lists deaths by group: 1, 2, 7, and 24, respectively. The registry information does not establish that these deaths were caused by treatment. No causal attribution should be inferred from the counts alone.
The listed serious-event terms include Hypertension, Vomiting, Infection, Dizziness, and Pain - Headaches, each reported as 33.3%, and Dyspnea, reported as 2.6%. The record does not give enough context in the registry record to interpret these percentages as treatment-attributable rates or to determine their denominators and event-level counting rules. Safety comparisons across these cohorts are also limited because the groups were not randomized like-for-like controls.
12. What the Result Does, and Does Not, Mean
This record describes a completed Phase I/II study of sorafenib with letrozole in postmenopausal women with hormone-receptor-positive locally advanced or metastatic breast cancer. Its primary purpose, as recorded, was to identify the sorafenib maximum tolerated dose with a fixed letrozole dose. The record also names clinical benefit rate, progression-free survival, and overall survival as secondary outcomes.
What the record does not establish is the numerical result of the primary endpoint or the magnitude and precision of any clinical outcome. The MTD result is not reported in the registry record. Numerical results for the listed secondary outcomes are also not present in the registry record for this analysis. A reference to the MTD in the Phase II arm description is not a substitute for a reported dose-finding result, and an outcome’s inclusion in the registry is not evidence of what the outcome showed.
The single-group design further limits interpretation. Without a randomized comparison, outcomes among participants cannot establish how those same outcomes would compare under another treatment. The dose cohorts are not a control group, and their safety counts should not be read as a controlled comparison. The registry also does not report sufficient detail to assess adjustment, missing data, analysis populations, or statistical uncertainty for efficacy outcomes.
Safety figures can still be read as registry-listed descriptive summaries, with caution about event definitions, attribution, and denominators. Counts of participants affected and deaths do not by themselves show whether treatment caused an event. The posted percentages for serious-event terms likewise should not be treated as comparative treatment effects.
In short, the record supports an account of the study’s purpose, design, and selected safety summaries. It does not support a conclusion about the clinical benefit of the combination, the size of an efficacy effect, or the certainty of such an effect. Those questions require reported outcome results and sufficient analysis details, which are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates the distinction between a dose-finding question and an efficacy comparison. MTD is intended to identify a dose according to tolerability, while clinical benefit, progression-free survival, and overall survival address different aspects of patient outcomes. Naming both types of endpoints in a registry does not make them interchangeable. Each requires its own result and appropriate interpretation.
It also illustrates why design information matters when reading group summaries. The registry identifies a single-group model, no masking, and allocation listed as NA. Dose-level cohorts may be useful in the study’s dose-escalation context, but they do not offer a randomized control comparison. Treating them as if they did would overstate what the design can show.
Another statistical lesson is that endpoint labels and completed status are not results. The registry describes the MTD question and lists secondary outcomes, yet the numerical primary and efficacy findings are not reported in the registry record. Without estimates and uncertainty measures, readers cannot assess the size or precision of an outcome. Without analysis details, readers also cannot determine how missing observations, analysis populations, or multiple outcomes were handled.
The adverse-event summaries show why safety counts need careful context. Affected counts and listed event percentages can describe what the record reports, but they do not establish causation or provide a fair comparison among nonrandomized cohorts. Interpretation depends on definitions, attribution, observation, and denominators, details that are not reported.
These distinctions are useful beyond this study: they help keep descriptions of design, planned questions, observed summaries, and causal conclusions separate. For this record, the strongest statistical account is a transparent one about what was planned and what is available, without filling gaps in the results.
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 information does not provide the numerical MTD result, despite identifying it as the primary outcome. It also does not provide numerical results for the listed clinical benefit rate, progression-free survival, or overall survival outcomes. No effect estimates, confidence intervals, or outcome-specific statistical tests are included in the registry record for this analysis.
The study is described as a single-group trial with no masking and no randomized allocation. As a result, the dose-level cohorts cannot serve as randomized controls. Comparisons of their event counts could be affected by differences in dose and other cohort characteristics. The registry does not provide an adjusted comparative analysis that would address such differences.
Important operational and analytic information is not reported in the registry record. This includes detailed eligibility criteria, dose-escalation decision rules, event definitions and attribution, participant-level follow-up, analysis populations, missing-data handling, and the statistical analysis plan. The registry also does not report a sample-size justification or how multiplicity across outcomes was addressed.
The safety summaries include at-risk and affected counts, deaths, and percentages for selected serious-event terms, but the available information is insufficient to establish causation or fully interpret denominators and event counting. Completion status and enrollment do not resolve these limitations. As a result, the record supports cautious description of the study and its reported safety summaries, but not a full assessment of efficacy, precision, or treatment-related risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I/II Trial of Letrozole and Sorafenib in Post-Menopausal Hormone-Receptor + Breast Cancer — NCT00634634.
- Registry record last updated 2023-11-09; status last verified 2023-10.
- Results first posted 2023-05-06.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT00634634 is a completed Phase I/II, single-group study sponsored by Rutgers, The State University of New Jersey. It examined sorafenib with letrozole in postmenopausal women with hormone-receptor-positive locally advanced or metastatic breast cancer. The registry lists enrollment of 52, no masking, and allocation as NA.
The primary outcome was maximum tolerated dose for sorafenib with fixed-dose letrozole, with a stated timeframe of twenty eight days. The registry describes a Phase I dose-escalation component and a Phase II arm at MTD, and lists clinical benefit rate, progression-free survival, and overall survival as secondary outcomes.
The numerical MTD result and numerical efficacy findings are not reported in the registry record. Safety summaries list adverse events and deaths by dose cohort, but they do not establish treatment causation or create a randomized comparison. Further analysis details, including missing-data methods and analysis populations, are also not reported.