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 Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer (NCT00082810), a na phase 2 study. The primary outcome is Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00082810 |
| Phase | Phase 2 |
| Condition | Estrogen Receptor-positive Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
The intended population was postmenopausal women with hormone receptor-positive, inoperable locally advanced or metastatic breast cancer that had progressed after previous first-line endocrine therapy. The registry lists estrogen receptor-positive, recurrent, stage IIIB, stage IIIC, and stage IV breast cancer among the conditions. The enrollment was 33. The registry record does not provide a fuller description of participant characteristics or the population included in the primary outcome analysis.
Intervention
Participants received fulvestrant with tipifarnib. The arm description specifies fulvestrant given intramuscularly on day 1 and oral tipifarnib twice daily on days 1-21, with courses repeating every 28 days if disease had not progressed and toxicity remained acceptable. The adverse-event group is titled “Fulvestrant 250 mg + Tipifarnib 300 mg.” The registry record does not give further dosing details in the primary outcome description.
Comparator
There was no separate comparator group: the registry identifies a single-group model and allocation as not applicable. Consequently, the record does not provide a concurrent control arm for estimating how outcomes would have differed under another treatment or under no study treatment. Comparisons with results from other trials would not be like-for-like controls and are not reported as part of this trial’s design.
Primary question
The primary question was how many participants met the definition of clinical benefit, consisting of complete response, partial response, or stable disease, during the timeframe of up to 24 weeks. Tumor response was assessed every three cycles using CT and RECIST 1.0 criteria. The registry record describes the endpoint but does not report the number who met it. Therefore, the endpoint’s result and its precision cannot be evaluated from the registry record.
3. Trial Design
This was a completed phase II trial sponsored by the National Cancer Institute. The registry describes a single-group, unmasked study with allocation marked not applicable. Enrollment was 33. Since every participant was assigned to the combination group in the registry description, the design does not make a randomized comparison between the combination and another treatment. It can describe outcomes among enrolled participants, but by itself cannot separate treatment effects from other influences on those outcomes.
The study concerned tipifarnib combined with fulvestrant as second-line therapy following progression after first-line endocrine therapy. The treatment description states that fulvestrant was administered intramuscularly on day 1 and tipifarnib was taken orally twice daily on days 1-21. Courses repeated every 28 days in the absence of progression or unacceptable toxicity. The registry does not provide further details about dose modifications, adherence, treatment exposure, or reasons for stopping treatment.
The primary outcome was the number of participants meeting the clinical benefit definition, with a timeframe of up to 24 weeks. Response was assessed every three cycles by CT using RECIST 1.0. Secondary outcomes listed in the registry are time to progression, duration of response, toxicity assessed by NCI CTCAE Version 3.0, and median overall survival. The record does not report results for those secondary outcomes in the registry record for this analysis.
The registry gives the study start as 2004-03 and primary completion as 2008-07, and identifies the trial status as completed. Completion is a study-status description; it does not itself establish that outcome data were reported or that a particular result was obtained. The registry record does not report the statistical plan, allocation procedures beyond the single-group designation, or details of the analysis population.
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 | Fulvestrant 250 mg + Tipifarnib 300 mg |
|---|---|
| STARTED | 33 |
| COMPLETED | 2 |
| NOT COMPLETED | 31 |
Reasons for not completing this period:
| Reason | Fulvestrant 250 mg + Tipifarnib 300 mg |
|---|---|
| Adverse Event | 3 |
| Progressive disease | 24 |
| Withdrawal by Subject | 4 |
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 | Fulvestrant 250 mg + Tipifarnib 300 mg |
|---|---|---|
| Participants analysed | 33 | |
| Age, Continuous | years | 61.0 (39 to 77) |
| Sex: Female, Male: Female | Participants | 33 |
| Sex: Female, Male: Male | Participants | 0 |
| Race/Ethnicity, Customized: Whites | participants | 14 |
| Race/Ethnicity, Customized: Black | participants | 3 |
| Race/Ethnicity, Customized: Hispanic | participants | 14 |
| Race/Ethnicity, Customized: Asian | participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD), measured over Up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
Clinical benefit rate (CBR) is defined in this record as the number of participants meeting any of the listed response categories: complete response (CR), partial response (PR), or stable disease (SD). The primary outcome timeframe is up to 24 weeks. Tumor response was assessed every three cycles by CT according to RECIST 1.0.
In the registry’s RECIST descriptions, CR means disappearance of all target lesions. PR requires at least a 30% decrease in the sum of the longest diameters of target lesions, relative to the baseline sum. PD is defined as at least a 20% increase relative to the smallest sum since treatment began, or the appearance of new lesions. SD means that neither the shrinkage threshold for PR nor the increase threshold for PD has been met, using the stated reference.
Combining CR, PR, and SD captures more than tumor shrinkage alone: it includes participants whose disease meets the stated definition of stability. Such a composite can describe the proportion of participants with disease control under the endpoint definition. In a single-group study, however, it does not provide a controlled estimate of what would have happened with a different treatment.
The registry record does not report the number meeting the CBR definition, the denominator used for the primary analysis, or an uncertainty interval. Thus, the endpoint definition is available, but the primary result cannot be quantified or assessed for precision from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives a clearly named primary endpoint and its assessment framework, but does not report the primary outcome count. It states that CBR is the number of participants with CR, PR, or SD through up to 24 weeks, and describes CT assessment every three cycles using RECIST 1.0. Without the number meeting that definition and the denominator analyzed, the rate of clinical benefit cannot be determined from the record. There is also no reported confidence interval with which to assess the precision of an estimate.
The design matters for interpretation. This was a single-group, unmasked phase II trial, not a randomized comparison. Even if an outcome count were available, it would describe outcomes in the treated group rather than quantify a treatment effect against a concurrent control. The registry record does not report a counterfactual comparison, and comparisons with other studies would not remove differences in participants, follow-up, outcome assessment, or other aspects of study conduct.
The enrollment was 33, but enrollment alone does not establish how many participants were included in the primary endpoint analysis. The registry record does not report the analysis population, the number evaluable for the primary outcome, or how missing response assessments were handled. Those details are important because the meaning of a count depends on who was eligible for inclusion and how unavailable outcome data were treated.
Safety information is reported separately. The adverse-event record lists 20 participants at risk for serious adverse events, of whom 20 were affected, and 33 at risk for other adverse events, of whom 15 were affected. Listed serious adverse-event terms include neutropenia, nausea, anemia, vomiting, hypocalcemia, and infection, with percentages recorded for each term. These observations describe events recorded in the treated group; they do not establish comparative safety because no control group is present. The record does not report deaths in the adverse-event group.
The registry lists time to progression, duration of response, toxicity, and median overall survival as secondary outcomes, but their results are not reported in the registry record for this analysis. Nor does the record describe a multiplicity adjustment or a statistical analysis plan. These omissions prevent an assessment of how secondary findings were analyzed or how uncertainty across multiple outcomes was addressed.
Overall, the registry supports a description of the study question, endpoint definition, treatment schedule, design, and some adverse-event counts. It does not support a numerical conclusion about primary clinical benefit, an estimate of treatment effect relative to a comparator, or a precise assessment of primary-outcome uncertainty.
9. Statistical Methods Explained
Statistical methods determine how observations are converted into estimates and how much uncertainty accompanies those estimates. For this trial, the registry record identifies a single-group model and a count-based primary outcome. It does not report the statistical analysis plan, the primary endpoint result, or a separate statistical analysis entry. As a result, the endpoint’s general statistical interpretation can be explained, but the specific methods used by the investigators cannot be reconstructed from the registry record.
What does a count-based endpoint represent?
The primary outcome is described as the number of participants who met the CBR definition: CR, PR, or SD. A count is the number of recorded participants satisfying an endpoint rule. To interpret that count as a rate, a reader also needs the relevant denominator: the number of participants considered for the endpoint under the analysis definition. The registry record does not report the primary outcome count or its analysis denominator, so a rate cannot be stated from these registry entries.
General statistical explanation: a proportion is a count of participants meeting a condition divided by a defined group of participants. The choice of denominator affects the interpretation. For example, an analysis might use all enrolled participants or only participants with an evaluable assessment, but the registry record does not state which population was used. No denominator should be inferred from enrollment alone.
How should uncertainty be understood?
General statistical explanation: an estimate from a study is subject to sampling variation. A confidence interval expresses a range of values compatible with the data under the method’s assumptions; a narrower interval generally indicates greater precision than a wider interval. The registry record does not report a confidence interval for CBR, and the missing outcome count and denominator mean that uncertainty around the primary result cannot be evaluated from the registry entries. A confidence interval would not by itself resolve limitations of the single-group design.
Likewise, a statistical test would address a specified hypothesis under stated assumptions; it would not automatically establish clinical importance or a causal effect. The registry record does not report a primary-outcome p-value, a hypothesis test, or the planned statistical criterion for interpreting results. No significance claim can therefore be made from the record.
What does the single-group design allow?
General statistical explanation: in a single-group study, outcome observations can describe what occurred among participants receiving the study regimen. A randomized control group supports a different kind of inference by providing a concurrent comparison under an assigned alternative. Because this trial is recorded as single-group, it does not offer that comparison. Differences between its participants and those in another study could reflect design, eligibility, follow-up, or other factors rather than treatment.
The study was unmasked according to the registry. Masking can reduce some forms of influence on assessments or reporting, depending on the outcome and how the study is conducted. The registry does not describe any additional safeguards or procedures for response assessment. The stated use of CT and RECIST 1.0 provides an outcome framework, but the record does not provide further information about assessment review or consistency.
What can the planning assumptions tell readers?
The registry contains general assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with target effects expressed as fractions of an observed effect. Those assumptions are not a description of this trial’s design, which is single-group. The registry explicitly characterizes the planning illustration as based on the observed effect rather than the trial’s own design. Any resulting sample-size figures are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect.
General statistical explanation: over-dispersion arises when variability in observed data exceeds what a chosen statistical model expects. Accounting for it can affect standard errors and uncertainty estimates. The registry entries do not indicate that over-dispersion was assessed or relevant to this binary count endpoint, and no particular model for the primary outcome is reported. It would therefore be inappropriate to attribute a model choice or adjustment to the investigators.
Why do analysis populations and missing observations matter?
The primary outcome depends on response assessments made over time. If an assessment is unavailable, the analysis must use a defined rule for whether and how that participant contributes to the endpoint. General statistical explanation: different missing-data rules can lead to different estimates, particularly when missingness is related to a participant’s health or treatment course. The registry does not report the missing-data rules, the number with missing assessments, or the primary analysis population. No assumption about those details is warranted.
The record also lists secondary outcomes with different statistical structures. Time to progression and overall survival are time-to-event outcomes; duration of response applies to participants with a response; toxicity is assessed as an adverse outcome. General statistical methods may differ across such endpoints, but the specific definitions, analysis methods, censoring rules, and results are not reported in the registry entries. The registry record identifies no separate statistical analysis entries. This limits evaluation of model assumptions, endpoint hierarchy, multiplicity, and robustness of findings.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity concerns arise when a study evaluates several outcomes, comparisons, or analyses. The registry lists a primary CBR endpoint and secondary outcomes of time to progression, duration of response, toxicity assessed by NCI CTCAE Version 3.0, and median overall survival. The registry record does not report a multiplicity strategy, such as an adjustment to account for testing several outcomes, nor does it state how primary and secondary results were prioritized in statistical interpretation. No separate statistical analysis entries are reported.
Missing data are also relevant because the primary endpoint requires response assessment through up to 24 weeks. The record does not report the number of participants with missing assessments, reasons for missingness, or the rule used to handle those observations. It does not identify whether the primary analysis included all enrolled participants or a subset defined by treatment exposure or evaluability. The enrollment of 33 should not be treated as the primary-outcome denominator without that information.
These gaps matter because exclusions or missing-response rules can change the group represented by an analysis and the interpretation of an endpoint count. General statistical explanation: when missingness is related to outcomes, treating unavailable observations as though they were interchangeable with observed ones can distort an estimate. Different assumptions or sensitivity analyses can show whether conclusions depend on those choices. The registry record does not report such analyses, so their use cannot be assessed.
The record also does not report how the secondary outcomes were analyzed, which analysis populations were used, or whether any prespecified hierarchy governed interpretation. These omissions do not establish that the trial lacked such procedures; they mean that they are not reported in 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 |
|---|---|---|---|
| Fulvestrant 250 mg + Tipifarnib 300 mg | 20 | 33 | 60.6% |
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 |
|---|---|
| Fulvestrant 250 mg + Tipifarnib 300 mg | 15 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | Fulvestrant 250 mg + Tipifarnib 300 mg |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 4 of 33 |
| Nausea | Gastrointestinal disorders | 3 of 33 |
| Anemia | Blood and lymphatic system disorders | 2 of 33 |
| Vomiting | Gastrointestinal disorders | 2 of 33 |
| Hypocalcemia | Metabolism and nutrition disorders | 2 of 33 |
| Infection | Infections and infestations | 1 of 33 |
| Diarrhea | Gastrointestinal disorders | 1 of 33 |
| Anorexia | Metabolism and nutrition disorders | 1 of 33 |
| Fatigue | General disorders | 1 of 33 |
| Cardiac Ischemia | Cardiac disorders | 1 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Fulvestrant 250 mg + Tipifarnib 300 mg |
|---|---|---|
| Nausea | Gastrointestinal disorders | 12 of 33 |
| Fatigue | General disorders | 12 of 33 |
| Diarrhea | Gastrointestinal disorders | 11 of 33 |
| Anemia | Blood and lymphatic system disorders | 8 of 33 |
| Neuropathy | Nervous system disorders | 7 of 33 |
| Anorexia | Metabolism and nutrition disorders | 6 of 33 |
| Hyperglycemia | Metabolism and nutrition disorders | 5 of 33 |
| Vomiting | Gastrointestinal disorders | 4 of 33 |
| Insomnia | Psychiatric disorders | 4 of 33 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 4 of 33 |
Serious events with the highest arm-level rate: neutropenia (12.1%), nausea (9.1%), anemia (6.1%), vomiting (6.1%), hypocalcemia (6.1%).
The adverse-event record lists 33 participants at risk for other adverse events, with 15 affected. For serious adverse events, it lists 33 at risk, with 20 affected. These are counts of participants recorded as affected in the respective categories; they are not measures of comparative risk because the study has no control group. The record lists no death count for this adverse-event group.
The listed serious adverse-event terms and percentages are neutropenia, 12.1%; nausea, 9.1%; anemia, 6.1%; vomiting, 6.1%; hypocalcemia, 6.1%; and infection, 3.0%. These percentages should be read as registry-reported values for the terms, not as mutually exclusive groups of participants. The registry record does not state whether a participant could contribute to more than one listed term, nor does it provide event-level detail or severity grades for these terms in the registry record.
General statistical explanation: adverse-event counts are descriptive safety observations. Their interpretation depends on the definitions used, how events were collected, exposure time, and whether the categories overlap. The registry identifies the safety group as “Fulvestrant 250 mg + Tipifarnib 300 mg,” but does not provide comparative safety estimates or a control group. These figures therefore describe recorded events in the trial group and do not establish how event frequency would compare with another treatment.
12. What the Result Does, and Does Not, Mean
This trial addresses a defined clinical question: the number of participants meeting a composite clinical-benefit definition after receiving tipifarnib with fulvestrant. The record describes the eligible clinical setting, the treatment schedule, the response criteria, and the timeframe of up to 24 weeks. It also records adverse-event counts and selected serious adverse-event terms.
The primary result itself is not reported in the registry entries available for this analysis. Without the CBR count and the denominator analyzed, there is no reported estimate of the proportion meeting the endpoint. Without an uncertainty interval, the precision of such an estimate cannot be described. The absence of these results from the registry record is not evidence that no outcomes occurred; it means the numerical primary result is not reported in the registry record.
Even a reported CBR estimate would need to be interpreted in light of the design. This was a single-group, unmasked phase II study, not a randomized comparison. Its data could describe outcomes among participants receiving the combination, but would not on their own establish the difference that would have occurred under another treatment. A comparison with an external study would not be equivalent to a concurrent randomized control.
The safety counts have a similarly bounded meaning. They record affected participants in the study group, with no control arm for comparison. They do not show whether the combination caused each event, nor do the listed figures establish a comparative safety profile. The registry entries do not provide the full event detail, exposure-adjusted summaries, or safety analysis methods needed for broader comparisons.
The completed status and stated enrollment describe the study record, not the strength or direction of the evidence. The trial’s clinical contribution cannot be judged from the primary outcome without its result, and its causal contribution is limited by the absence of a comparator. Accordingly, the registry supports an account of the question and methods, but not a claim that the combination did or did not produce clinical benefit.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how endpoint definition and design shape what a result can mean. Its primary outcome is not simply tumor shrinkage: the registry defines clinical benefit using CR, PR, or SD. The response framework uses RECIST 1.0 and specifies how target-lesion changes distinguish these categories. This makes clear that the endpoint combines response and disease stability, rather than counting only complete or partial responses.
The single-group structure is equally important. A count of participants meeting the endpoint could describe what occurred in the treatment group, but would not provide a randomized estimate of the combination’s effect relative to another option. This distinction remains essential even when an endpoint is clinically interpretable: an outcome measure and a causal comparison answer different questions.
The record also demonstrates why results and analysis details are both necessary. Enrollment and endpoint definitions do not supply the primary count, denominator, uncertainty interval, or missing-data rules. Without those details, readers cannot evaluate the magnitude or precision of the endpoint estimate. A completed trial record can still leave key statistical results unreported.
Finally, the adverse-event information illustrates the difference between descriptive safety reporting and comparative safety inference. Counts and term percentages summarize events recorded in the study group, while the absence of a control group limits comparison. Taken together, the trial’s statistical importance lies in the clear distinction between the question it set out to answer, the outcomes its registry describes, and the inferences the available record can support.
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 limitation for interpreting this trial’s efficacy question is that the registry record does not report the primary outcome count or analysis denominator. It gives the CBR definition and timeframe, but those alone do not allow calculation or interpretation of the endpoint result. The record also does not report a confidence interval or primary-outcome test.
The single-group, unmasked design limits causal and comparative interpretation. There is no concurrent control group, so the registry cannot show how the outcomes would compare with another treatment under the same study conditions. Unmasked status may also matter for outcome assessment, although the record does not describe whether additional procedures were used to reduce assessment-related influence.
The registry does not report participant characteristics beyond the broad eligibility description and listed conditions. It also does not provide the number included in the primary analysis, missing assessment counts, handling of missing data, or analysis-population definitions. Thus, readers cannot determine from these registry entries whether the enrolled group and analyzed group were the same or how unavailable response assessments were treated.
The record lists secondary outcomes but does not provide their results or the methods used to analyze them. It does not report a multiplicity approach, an analysis plan, or details of response review and follow-up. For safety, the record gives affected counts and selected serious-event terms but does not provide event-level detail, exposure-adjusted estimates, or comparative data. These limitations restrict the conclusions to the documented design, endpoint definitions, and reported safety summaries; they do not establish what was or was not included in analyses that are not reported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer — NCT00082810.
- Registry record last updated 2018-11-01; status last verified 2018-10.
- Results first posted 2015-08-10.
- 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
NCT00082810 is a completed phase II, single-group, unmasked trial sponsored by the National Cancer Institute. Enrollment was 33. It studied tipifarnib with fulvestrant in postmenopausal women with hormone receptor-positive, inoperable locally advanced or metastatic breast cancer that had progressed after first-line endocrine therapy.
The primary endpoint was the number meeting the clinical benefit definition of CR, PR, or SD, assessed by CT using RECIST 1.0 through up to 24 weeks. The registry record does not report the primary outcome count, denominator, or precision estimate. It lists time to progression, duration of response, toxicity, and median overall survival as secondary outcomes, without results in the registry record.
The adverse-event record reports 20 affected participants among 33 at risk for serious adverse events and 15 affected among 33 at risk for other adverse events. The single-group design supports descriptive interpretation, not a controlled treatment comparison.