This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study Of Bosutinib With Capecitabine In Solid Tumors And Locally Advanced Or Metastatic Breast Cancer (NCT00959946), a non-randomized phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) - Part 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00959946 |
| Phase | Phase 1, Phase 2 |
| Condition | Advanced Breast Cancer (Parts 1 and 2), Advanced Pancreatic Cancer (Part 1), Advanced Colorectal Cancer (Part 1) |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Part 1 included participants with advanced breast, pancreatic, colorectal, or biliary tract cancer, or glioblastoma multiforme. Part 2 was for breast cancer, described in the official title as ErbB2 negative locally advanced or metastatic breast cancer. The primary endpoint used a DLT-evaluable population: participants who received at least 14 doses of bosutinib and at least 10 doses of capecitabine in the first 21 days of treatment, or who experienced a DLT in that period.
Intervention
The study combined oral bosutinib with capecitabine. In Part 1, the doses were varied to assess tolerability and identify dose combinations suitable for further study. Part 2 was planned to use the highest tolerated dose identified in Part 1.
Comparator
There was no randomized control group. The study was non-randomized, open-label, and single-group in its recorded model. Dose groups in Part 1 were not like-for-like controls: they differed by assigned dose combination and were part of dose exploration.
Primary question
Which bosutinib and capecitabine dose combinations met the study’s definition of a maximum tolerated dose in Part 1? The definition was based on the observed dose-limiting toxicity rate during the first 21 days. The registry record does not report the resulting MTD finding.
The study also aimed to assess safety, how the body handled the combination, and preliminary anti-tumor activity. Part 1 included several solid tumor types, while Part 2 focused on breast cancer. Those aims describe what the study set out to assess; they do not, by themselves, establish what the observed results were.
3. Trial Design
This was a phase 1/2, open-label study of bosutinib combined with capecitabine. The registry lists non-randomized allocation and a single-group model, with no masking. The study enrolled 32 participants and was sponsored by Pfizer. It started in 2009-09, had primary completion in 2011-03, and is listed as terminated. The reason for termination is not reported in the registry record.
The trial had two parts with different aims. Part 1 was dose exploration across advanced cancers. Participants received varying doses of both drugs, with the stated purpose of determining the highest tolerated dose of the combination. The dose combinations listed in the adverse-event groups include bosutinib 200 mg, 300 mg, or 400 mg with capecitabine 625 mg/m^2, 750 mg/m^2, or 1000 mg/m^2. These recorded groups should not be read as randomized treatment arms or as a controlled comparison.
Part 2 was intended to evaluate the combination in breast cancer at the highest tolerated dose identified in Part 1. The brief summary describes this plan, but the Part 2 arm description and the actual Part 2 results are not reported in the registry record. The study also lists pharmacokinetic measures, including maximum observed plasma concentration, time to maximum concentration, apparent volume of distribution, and area under the curve.
General: early-phase dose-finding studies commonly prioritize tolerability and dose selection rather than a controlled estimate of comparative efficacy. Because this study did not use randomized allocation or a like-for-like control group, differences between its dose groups cannot be interpreted as causal treatment comparisons.
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: Study was pre-maturely terminated after part 1 (safety lead-in phase) of study and hence, planned treatments of part 2, Bosutinib 300 milligram (mg) + Capecitabine 1000 mg/square meter (mg/m\^2) (Part 2): estrogen receptor positive (ER+) and Bosutinib 300 mg+Capecitabine 1000 mg/m\^2 (Part 2): estrogen receptor negative (ER-), were not administered.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|
| STARTED | 2 | 4 | 4 | 5 | 4 | 9 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 2 | 4 | 4 | 5 | 4 | 9 |
Reasons for not completing this period:
| Reason | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 2 | 1 | 0 | 1 |
| Death | 0 | 0 | 0 | 0 | 0 | 1 |
| Disease Progression | 2 | 4 | 2 | 4 | 4 | 6 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: DLT evaluable population included all participants who received at least 14 doses of bosutinib and at least 10 doses of capecitabine in the first 21 days of treatment or had experienced a DLT within the first 21 days of treatment. N (number of participants analyzed) signifies participants who were evaluable for this measure.
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 9 groups are shown.
| Characteristic | Unit | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 2 | 4 | 4 | 5 | 4 | 9 | |
| Age Continuous | Years | 53.0 (SD 4.24) | 56.8 (SD 16.32) | 67.3 (SD 10.05) | 63.0 (SD 8.43) | 56.0 (SD 8.45) | 63.8 (SD 5.49) |
| Sex: Female, Male: Female | Participants | 2 | 1 | 2 | 4 | 3 | 4 |
| Sex: Female, Male: Male | Participants | 0 | 3 | 2 | 1 | 1 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) - Part 1, measured over Part 1 Baseline up to Day 21.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was Maximum Tolerated Dose (MTD) in Part 1, recorded as a number with mg as the unit. The endpoint concerns dose selection: it is intended to identify dose combinations whose observed dose-limiting toxicity (DLT) rate falls below the study’s threshold. The registry defines the MTD contour as dose combinations achieving a DLT rate of <1/3.
The toxicity assessment covered the first 21 days of treatment. Listed DLTs include grade 3/4 nausea, vomiting, diarrhea, or asthenia lasting more than 3 days; grade 4 hematologic toxicities; and delayed study treatment administration due to dose toxicities by more than 3 weeks. The registry also describes rules under which no MTD would be recommended for a capecitabine dose level, depending on toxicity across bosutinib dose levels.
General: an MTD endpoint is used in dose-finding research to guide which dose combination may be taken forward for further assessment. It is not itself a measure of comparative anti-tumor benefit. The registry record provides the endpoint definition and analysis population but does not report the MTD result or the observed DLT counts by dose combination. Therefore, the dose selected, if any, is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a dose-finding study, but it does not report the primary MTD finding. It supplies the endpoint definition, timeframe, DLT criteria, and a definition of the DLT-evaluable population, but no observed MTD values or dose-specific DLT rates. Consequently, the posted record does not establish which dose combination met the study’s MTD criteria.
The adverse-event summary gives participant counts at risk and counts affected by serious and other adverse events for eight Part 1 dose groups. Serious adverse events were reported for 0 of 2 participants in the bosutinib 200 mg plus capecitabine 625 mg/m^2 group, 2 of 4 in the 200 mg plus 750 mg/m^2 group, 2 of 4 in the 200 mg plus 1000 mg/m^2 group, 2 of 5 in the 300 mg plus 625 mg/m^2 group, 0 of 4 in the 300 mg plus 750 mg/m^2 group, 3 of 9 in the 300 mg plus 1000 mg/m^2 group, 0 of 2 in the 400 mg plus 750 mg/m^2 group, and 1 of 2 in the 400 mg plus 1000 mg/m^2 group. These are descriptive counts within the recorded groups, not controlled estimates of dose effects.
The registry lists other adverse events for all participants at risk in each of the eight groups: 2 of 2, 4 of 4, 3 of 4, 5 of 5, 4 of 4, 9 of 9, 2 of 2, and 2 of 2, respectively. The record does not define the “other” category further in the information. These counts should not be conflated with DLTs: the adverse-event summary and primary endpoint have different stated purposes, and the posted record does not link individual adverse events to the MTD analysis.
Serious adverse event terms listed in the record include atrial fibrillation, chest pain, and dyspnoea, each reported as 50.0%, and bronchitis, neoplasm malignant, and pancreatic carcinoma, each reported as 25.0%. The denominator and calculation basis for these percentages are not reported in the registry record, so they should not be treated as participant-level risks.
General: small groups yield imprecise estimates, and counts can change substantially with a small number of participants. The dose groups also differ in size and dose combination and were not randomized. The record does not report confidence intervals for these adverse-event counts, so the precision of each group’s rate cannot be assessed from the posted results alone. The results are descriptive and do not support a causal comparison among doses.
9. Statistical Methods Explained
The primary analysis was framed around dose-limiting toxicity during the first 21 days and the identification of an MTD contour. The registry defines that contour as dose combinations with an observed DLT rate of <1/3. It also states that DLT rates for reporting groups with at least one allocated cohort were estimated as the proportion of DLTs observed in those first 21 days. The record does not report a statistical model for dose-response estimation or a method for combining information across dose groups.
What does the MTD rule mean?
General: a toxicity threshold provides a decision rule for dose selection. A dose combination below the threshold may be considered tolerable under the protocol’s definition, while combinations at or above the threshold raise a different tolerability concern. The rule is specific to the defined timeframe and toxicity criteria; it does not summarize every possible safety outcome over the full study. Here, the registry’s endpoint description also includes pre-defined circumstances in which no MTD would be recommended for a capecitabine dose level. The record does not state how those rules were applied to the observed participants.
Who counted in the primary endpoint population?
The DLT-evaluable population included participants who received at least 14 doses of bosutinib and at least 10 doses of capecitabine in the first 21 days of treatment, or who experienced a DLT within the first 21 days. This definition matters because it determines which participants contribute to the dose-finding endpoint. The registry record says that N signifies participants analyzed, but the remainder of that description is incomplete. The number analyzed for the MTD endpoint is not reported in the registry record.
How should the adverse-event counts be read?
The adverse-event groups report numbers at risk and numbers affected. These are descriptive participant counts within each listed dose group. General: a proportion is a way to describe how many participants in a group experienced an event, but its interpretation depends on consistent definitions, follow-up, and a clear denominator. The posted record gives group denominators for serious and other adverse events, but it does not report confidence intervals or a comparative analysis of these groups. The listed serious-event terms are percentages without a stated denominator in the record, limiting interpretation of their frequency.
What can be inferred from the design?
General: randomization helps balance known and unknown prognostic factors between treatment groups. Without randomization, a difference between groups may reflect differences in participants, dose choices, follow-up, or chance rather than a dose effect. In a dose-finding study, groups are often used to explore tolerability rather than to estimate comparative treatment effects. The registry identifies this trial as non-randomized and does not describe a concurrent control group. No comparative causal conclusion should be drawn from the adverse-event counts.
The study is open-label, meaning masking was not used. General: knowledge of assigned treatment can influence reporting, assessment, or management of outcomes, particularly outcomes that require judgment. The registry record does not describe blinding procedures for any specific assessment.
The registry lists Best Overall Response in Part 1 and progression-free survival, clinical benefit rate, duration of response, and pharmacokinetic measures in Part 2 among secondary outcomes. It does not report numerical results for these measures in the information recorded. No analysis entries are listed. The analysis methods for secondary outcomes, the statistical plan, and any planned interim analyses are not reported in the registry record.
General: a confidence interval expresses the uncertainty around an estimated quantity under its statistical assumptions. It can show whether the estimate is precise or compatible with a broad range of values. No confidence intervals for the primary endpoint or adverse-event summaries are reported in the registry record. Thus, the posted counts can be described, but their sampling uncertainty cannot be quantified from the recorded results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures. Alongside the primary MTD endpoint, secondary outcomes include Best Overall Response in Part 1 and progression-free survival, clinical benefit rate, duration of response, and pharmacokinetic measures in Part 2. The listed pharmacokinetic outcomes are maximum observed plasma concentration, time to reach maximum observed plasma concentration, apparent volume of distribution, and area under the curve from time zero to the last quantifiable concentration.
Multiplicity arises when several outcomes, dose groups, or analyses are examined. General: without an appropriate plan, multiple statistical tests can increase the chance that at least one result appears notable by chance. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a prespecified strategy for interpreting multiple comparisons. It also lists zero analyses, so no analysis-specific results or multiplicity handling are recorded.
Missing-data methods are not reported in the registry record. The MTD population definition specifies minimum treatment exposure for participants without an early DLT, but the record does not explain how incomplete toxicity assessments, withdrawals, or missing outcome measurements were handled. The reason for termination is also not reported. These gaps prevent assessment of whether missing observations or early study closure affected the analyses.
The record identifies the DLT-evaluable population and gives its eligibility rule, but the analyzed number is not reported in the registry record. Analysis populations for the secondary outcomes are also not reported. General: transparent population definitions and missing-data methods are important because excluding participants or measurements can affect estimates, especially in small dose groups.
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 |
|---|---|---|---|
| Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | 0 | 2 | 0.0% |
| Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | 2 | 4 | 50.0% |
| Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 2 | 4 | 50.0% |
| Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 2 | 5 | 40.0% |
| Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 0 | 4 | 0.0% |
| Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 3 | 9 | 33.3% |
| Bosutinib 400 mg + Capecitabine 750 mg/m^2 (Part 1) | 0 | 2 | 0.0% |
| Bosutinib 400 mg + Capecitabine 1000 mg/m^2 (Part 1) | 1 | 2 | 50.0% |
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 |
|---|---|
| Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | 2 of 2 |
| Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | 4 of 4 |
| Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | 3 of 4 |
| Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | 5 of 5 |
| Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | 4 of 4 |
| Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) | 9 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | 0 of 2 | 0 of 4 | 1 of 4 | 0 of 5 | 0 of 4 | 1 of 9 |
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 2 | 0 of 4 | 1 of 4 | 0 of 5 | 0 of 4 | 1 of 9 |
| Anaemia | Blood and lymphatic system disorders | 0 of 2 | 0 of 4 | 0 of 4 | 1 of 5 | 0 of 4 | 0 of 9 |
| Gastrointestinal obstruction | Gastrointestinal disorders | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 4 | 1 of 9 |
| Asthenia | General disorders | 0 of 2 | 0 of 4 | 0 of 4 | 1 of 5 | 0 of 4 | 0 of 9 |
| Glioblastoma multiforme | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 4 | 1 of 9 |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 2 | 1 of 4 | 0 of 4 | 0 of 5 | 0 of 4 | 0 of 9 |
| Hemiparesis | Nervous system disorders | 0 of 2 | 0 of 4 | 0 of 4 | 1 of 5 | 0 of 4 | 0 of 9 |
| Renal impairment | Renal and urinary disorders | 0 of 2 | 1 of 4 | 0 of 4 | 0 of 5 | 0 of 4 | 0 of 9 |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 4 | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bosutinib 200 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 200 mg + Capecitabine 1000 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 625 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 750 mg/m^2 (Part 1) | Bosutinib 300 mg + Capecitabine 1000 mg/m^2 (Part 1) |
|---|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 2 of 2 | 1 of 4 | 2 of 4 | 3 of 5 | 3 of 4 | 8 of 9 |
| Nausea | Gastrointestinal disorders | 0 of 2 | 4 of 4 | 2 of 4 | 2 of 5 | 1 of 4 | 4 of 9 |
| Fatigue | General disorders | 0 of 2 | 2 of 4 | 1 of 4 | 3 of 5 | 1 of 4 | 5 of 9 |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 1 of 2 | 1 of 4 | 2 of 4 | 0 of 5 | 1 of 4 | 3 of 9 |
| Vomiting | Gastrointestinal disorders | 0 of 2 | 3 of 4 | 1 of 4 | 0 of 5 | 1 of 4 | 2 of 9 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 2 | 2 of 4 | 0 of 4 | 1 of 5 | 0 of 4 | 3 of 9 |
| Abdominal pain | Gastrointestinal disorders | 1 of 2 | 0 of 4 | 1 of 4 | 0 of 5 | 0 of 4 | 3 of 9 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 2 | 0 of 4 | 1 of 4 | 1 of 5 | 0 of 4 | 2 of 9 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 2 of 4 | 0 of 4 | 1 of 5 | 1 of 4 | 1 of 9 |
| Mucosal inflammation | General disorders | 1 of 2 | 0 of 4 | 1 of 4 | 0 of 5 | 0 of 4 | 2 of 9 |
Serious events with the highest arm-level rate: atrial fibrillation (50.0%), chest pain (50.0%), dyspnoea (50.0%), bronchitis (25.0%), neoplasm malignant (25.0%).
The adverse-event summary reports serious and other events separately for each Part 1 dose group. For each group, “at risk” is the number of participants in the recorded denominator and “affected” is the number reported with that event category. For example, the bosutinib 200 mg plus capecitabine 625 mg/m^2 group lists 2 participants at risk for serious events and 0 affected; the bosutinib 300 mg plus capecitabine 1000 mg/m^2 group lists 9 at risk and 3 affected. The counts are descriptive and do not establish a dose-related pattern.
The “other” adverse-event counts range across the groups as recorded: 2 of 2, 4 of 4, 3 of 4, 5 of 5, 4 of 4, 9 of 9, 2 of 2, and 2 of 2. The exact definition of “other” is not reported in the registry record. The record lists no death counts; the death field is null, which should not be interpreted as confirmation that no deaths occurred.
Several serious adverse-event terms are listed with percentages, but the denominator and whether these are participant-level or event-level percentages are not reported in the registry record. These figures therefore cannot be directly interpreted as risks among all enrolled participants. General: adverse-event comparisons are particularly uncertain with small, non-randomized groups, and they should not be read as evidence that one dose is safer than another.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a phase 1/2, open-label, non-randomized study of bosutinib with capecitabine, with dose exploration in Part 1 and a planned breast-cancer-focused Part 2. It also establishes the study’s primary endpoint definition: assess DLT rates during the first 21 days and identify dose combinations meeting the stated MTD criterion. The record reports adverse-event counts for the listed Part 1 dose groups.
It does not report the primary MTD result, dose-specific DLT counts, or the dose selected for Part 2. It also does not report numerical results for the listed tumor response, progression, clinical benefit, duration of response, or pharmacokinetic outcomes. Therefore, the registry record cannot establish the extent of anti-tumor activity or how the body handled the combination based on those outcomes.
The adverse-event counts describe what was recorded in groups of different sizes. They do not provide a randomized comparison, and they do not show that an observed difference was caused by dose. No confidence intervals are reported for these summaries, so their precision is not given. The serious-event term percentages lack a reported denominator, which further limits interpretation.
General: an early-phase dose-finding study and a controlled efficacy trial answer different questions. Dose exploration can inform tolerability and subsequent study planning, but it is not a substitute for a randomized comparison when the aim is to estimate comparative effects. Here, the registry’s design and missing outcome results do not support conclusions about comparative benefit or harm. The study’s termination status is recorded, but the reason is not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why the endpoint definition and the reported result need to be considered separately. The registry specifies a toxicity threshold, a 21-day assessment period, and criteria for who could contribute to the DLT analysis. Those details make the intended dose-selection question clear. However, the primary MTD result and the number analyzed are not reported, so the endpoint’s actual conclusion cannot be evaluated from the registry record.
The record also highlights the distinction between dose-finding and treatment comparison. Participants were not randomized among dose groups, and the study was open-label. The group counts can describe recorded adverse events, but they do not isolate the effect of dose from differences in the groups or other factors. This distinction is essential when interpreting early-phase evidence.
Finally, the listing of multiple secondary outcomes does not substitute for their results or for a stated analysis plan. The registry names response, progression, clinical benefit, duration, and pharmacokinetic measures, but reports no analysis entries. Without analysis results, a multiplicity strategy, and details on missing outcomes, the reader cannot assess how those endpoints were evaluated. The study is therefore informative about the questions the investigators intended to address, while the registry record leaves key statistical findings unreported.
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 primary result is not reported in the registry record. The MTD endpoint description gives the decision threshold and DLT criteria, but no dose-specific DLT counts, estimated toxicity rates, MTD recommendation, or analyzed sample size are included. The population description ends before fully specifying how N was defined.
The record reports 32 enrolled participants, but the number assigned to each Part 1 dose group and the number included in the primary analysis are not fully reconciled in the recorded information. The dose-group adverse-event denominators are small and differ across groups. No confidence intervals are reported for the adverse-event counts or listed percentages, and the denominator for the serious-event term percentages is not stated.
Part 2’s intended approach is described in the brief summary, but the Part 2 arm description and numerical outcomes are not reported in the registry record. The reason the study was terminated is not reported. The record does not state how missing outcomes were handled, whether analyses were interim or final, or which statistical procedures were used for the secondary outcomes.
General: these reporting gaps limit reproducibility and make it difficult to evaluate precision, selection effects, and the potential impact of incomplete follow-up. The non-randomized, open-label design also limits causal interpretation of between-group differences. These limitations concern what can be concluded from the registry record; they do not establish why results or methods were not reported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Of Bosutinib With Capecitabine In Solid Tumors And Locally Advanced Or Metastatic Breast Cancer — NCT00959946.
- Registry record last updated 2013-02-22; status last verified 2013-01.
- Results first posted 2013-02-22.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00959946 is a phase 1/2, open-label, non-randomized study of bosutinib with capecitabine in solid tumors and locally advanced or metastatic breast cancer. Part 1 explored dose combinations in several advanced cancers, with the primary endpoint defined as MTD based on DLTs during the first 21 days. Part 2 was planned to focus on breast cancer at the highest tolerated dose.
The record lists 32 enrolled participants, a start date of 2009-09, primary completion in 2011-03, and a status of terminated. It reports adverse-event counts for eight Part 1 dose groups and lists secondary response, progression, clinical benefit, duration, and pharmacokinetic outcomes. The primary MTD result, numerical secondary outcome results, reason for termination, and detailed statistical analysis plan are not reported in the registry record.