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 Bevacizumab and Erlotinib for Patients With Hormone Refractory Prostate Cancer (NCT00996502), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose of Docetaxel in Combination With Erlotinib, Bevacizumab, and Prednisone (Phase I).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00996502 |
| Phase | Phase 1, Phase 2 |
| Condition | Prostate Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Columbia University |
| Results posted | Yes |
2. Clinical Question
The study asked whether bevacizumab, erlotinib, docetaxel, and prednisone could be administered together at a tolerable dose to patients with hormone refractory prostate cancer, and whether the regimen showed signs of activity. Its primary objective was to identify the maximum tolerated dose of docetaxel in combination with the other drugs. The registry names this as a Phase I endpoint assessed after three 21-day cycles. It also describes evaluation of the regimen’s effectiveness through prostate-specific antigen and objective tumor response.
Population
Patients with hormone refractory prostate cancer. The registry lists prostate cancer as the condition and records enrollment of 4 participants. Further eligibility criteria and characteristics of those enrolled are not reported in the registry record.
Intervention
A combination regimen of bevacizumab, erlotinib, docetaxel, and prednisone. The registry describes dose escalation of docetaxel in Phase I alongside standard doses of bevacizumab and erlotinib, with the safest dose intended for evaluation in Phase II.
Comparator
There was no separate comparator group: the registry describes a single-group study with no allocation. Results therefore cannot be framed as a randomized comparison against another treatment or a control condition.
Primary question
What maximum tolerated dose of docetaxel, in combination with erlotinib, bevacizumab, and prednisone, was identified after three 21-day cycles? The registry record does not report an answer; it says the data will not be analyzed.
The registry’s brief summary describes two planned parts: an initial dose-escalation part and a subsequent part in which participants would receive the safest dose. It states that 18 patients would enter the first part and an additional 37 the second. These are planned numbers in the summary, not the enrollment reported for the study. The record gives enrollment as 4 and status as terminated. Thus, the clinical question is documented, but the posted record does not supply an analyzed estimate of dose tolerance or tumor response.
3. Trial Design
The registry classifies this as a Phase I/II, single-group study of a four-drug combination. Allocation is listed as not applicable and masking as none. The record does not describe a randomized assignment or a blinded comparison. The sponsor is Columbia University. The study began in 2006-07, has a primary completion date of 2010-03, and is listed as terminated.
The brief summary describes a dose-escalation stage followed by a stage intended to evaluate the regimen at the safest dose identified earlier. In the first stage, docetaxel doses would increase while bevacizumab and erlotinib were given at standard doses; prednisone is also part of the combination regimen. The summary states that 18 patients would be enrolled in the first part and an additional 37 in the second. These statements describe the planned study, whereas the registry reports enrollment of 4. The record does not explain why enrollment was lower than the planned numbers or give a reason for termination.
The primary outcome is titled maximum tolerated dose of docetaxel with the other three drugs, with assessment after three 21-day cycles. The listed secondary outcomes include objective response rate at the recommended Phase II dose, overall survival rate, and the proportion alive at one year in Phase II. The registry lists four outcome measures in total, but supplies no analyzed outcome estimates and no statistical analyses.
Although the registry records the design and intended outcomes, important protocol details are not reported in the registry record. These include the formal dose-escalation rules, toxicity criteria, eligibility criteria, analysis populations, and statistical analysis plan. The registry also does not report whether the planned second stage opened or how many participants received each dose. The record states that the principal investigator left the institution, attempts to contact the investigator were unsuccessful, and Columbia would not have access to the data; as a result, the data would not be analyzed. Enrollment should therefore not be interpreted as the number who completed treatment or contributed to any particular outcome.
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 | Combination Regimen |
|---|---|
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The principal investigator has left the institution. Attempts to contact the PI have been unsuccessful. Columbia will never have access to the data. Thus, data will not be analyzed. The only information available is the number of participants who started and completed the study, which was last reported to and approved by the IRB in March 2010.
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 | Combination Regimen |
|---|---|---|
| Participants analysed | 4 | |
| Age, Customized: 18 years and older | participants | 4 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 4 |
| Region of Enrollment: United States | participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose of Docetaxel in Combination With Erlotinib, Bevacizumab, and Prednisone (Phase I), measured over After three 21-day cycles.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of docetaxel when given with erlotinib, bevacizumab, and prednisone. The registry specifies assessment after three 21-day cycles. In a dose-finding study, the general purpose of this endpoint is to identify a dose that can be carried forward for further evaluation while taking treatment-related toxicity into account. This makes dose tolerance the central Phase I question, distinct from an estimate of whether the regimen improves a clinical outcome.
The registry does not provide the toxicity threshold used to define the maximum tolerated dose, the dose-escalation decision rules, or the observed dose-level findings. It also does not state which adverse events counted toward the endpoint or how events were attributed to treatment. Consequently, the endpoint’s intended meaning can be described, but the value observed in this study cannot be recovered from the posted record.
The planned Phase II assessment was intended to examine activity, including prostate-specific antigen and objective tumor response. The listed secondary outcomes also include objective response rate at the recommended Phase II dose, overall survival rate, and the proportion alive at one year. These endpoints address different questions from the primary dose-finding endpoint. No estimates for them are reported, and the record says the study data would not be analyzed. The primary endpoint therefore remains an intended measure rather than a reported result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record documents a planned dose-finding and activity study, not an analyzed estimate of efficacy or safety. Its primary endpoint was the maximum tolerated dose of docetaxel in the four-drug regimen after three 21-day cycles. No dose was reported as the maximum tolerated dose, and no participant-level or group-level endpoint result is posted. The registry specifically says that data would not be analyzed because the principal investigator had left the institution, contact attempts were unsuccessful, and Columbia would not have access to the data.
Enrollment is listed as 4, while the brief summary describes plans for 18 participants in Phase I and an additional 37 in Phase II. The planned enrollment and the recorded enrollment answer different questions: the former describes the design described in the summary; the latter is the registry’s recorded enrollment. The record does not explain the difference, give a reason for termination, or establish how many enrolled participants completed treatment or had endpoint assessments.
The registry lists secondary outcomes, but no response rate, survival estimate, or other analyzed outcome is reported. It also lists no statistical analyses. Without estimates and measures of uncertainty, there is no basis in the posted record for judging the magnitude or precision of a treatment effect. Because the study is single-group, it would in any case not provide a randomized estimate of the regimen’s effect relative to a control group.
The adverse-event entries list zero participants at risk, zero affected, and zero deaths in the combination-regimen group. Those entries should not be read as proof that no adverse events occurred. The same record says that data were unavailable for analysis, and the posted adverse-event entries do not establish the completeness of safety ascertainment or explain how the values were generated. The study’s intended safety question therefore remains unanswered by the available record.
General statistical interpretation: an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the data under the method’s assumptions; it is not a guarantee that the true value lies within that range. Here, neither an endpoint estimate nor a confidence interval is reported. Precision cannot be assessed, and statistical significance cannot be evaluated from the registry record.
Accordingly, the posted information supports conclusions about the study’s intended design, recorded enrollment, status, and missing analysis, but not about the regimen’s observed tolerability or activity. The absence of analyzed results is not evidence of either benefit or lack of benefit. It is a limit on what can be concluded from this record.
9. Statistical Methods Explained
The registry describes a Phase I/II, single-group study with dose escalation, but does not report a statistical analysis plan. Statistical methods specific to the trial, including the dose-escalation algorithm, stopping rules, toxicity definitions, and approach to summarizing outcomes, are not reported in the registry record. The explanations below are general statistical context and should not be taken as a description of methods actually used in this study.
What does a maximum tolerated dose represent?
General: dose-finding studies assess whether different dose levels can be administered within predefined safety limits. A maximum tolerated dose is ordinarily determined by combining observed toxicity with a prespecified rule for deciding which dose is acceptable. The result depends on the dose levels tested, the time window used to observe toxicity, the definition of a dose-limiting event, and the escalation or de-escalation rule. Those details are necessary to interpret a reported dose. The registry identifies the endpoint and says it was assessed after three 21-day cycles, but it does not give the decision rules or the dose-specific safety findings. No maximum tolerated dose can therefore be inferred from the record.
Why does the single-group structure matter?
General: an uncontrolled, single-group study can describe outcomes among participants receiving the study regimen. It cannot by itself separate the effects of the regimen from changes that might have occurred without it, differences in participant characteristics, or other influences on outcomes. Randomized comparison is one way to address such differences, but this registry lists no allocation and describes a single group. The design is consistent with the stated dose-finding purpose, but it does not yield a randomized treatment contrast.
For a Phase I endpoint, the principal statistical information would ordinarily include the number assessed at each dose, the observed toxicities during the specified window, and the rule used to select a dose. None of these results is reported. For the planned Phase II activity outcomes, interpretable summaries would ordinarily require clear outcome definitions, assessment timing, counts or estimates, and an account of missing observations. Those details and results are also absent. These are general considerations, not claims that a particular analysis was performed.
What would an uncertainty interval add?
General: a point estimate alone gives a central summary, while an uncertainty interval communicates how much the estimate may vary because of limited data and sampling. For a proportion, uncertainty depends in part on the number of participants with usable outcome information and the number meeting the outcome definition. For survival outcomes, methods also need to account for follow-up time and censoring. The registry provides no estimates or intervals for the listed outcomes, and it does not report participant-level follow-up or outcome status. Neither precision nor the reliability of a potential estimate can be assessed.
Small studies can produce highly unstable estimates, but no further numerical precision assessment is possible from the information posted. The recorded enrollment is 4; it does not establish the number included in each endpoint analysis. In particular, enrollment cannot be substituted for the denominator of an analyzed response or safety outcome. The record says the only information available was the number who started and completed the study, but the corresponding counts are not given in the registry text.
How should dose escalation and over-dispersion be understood?
General: dose-escalation designs use accumulating safety information to guide which dose is given next. Different designs make different assumptions and use different rules; the label “dose escalation” alone does not identify the method. It would be inappropriate to infer a particular cohort structure or algorithm from the brief summary. The registry’s arm description contains partial dose information, but the escalation protocol and complete dose-level results are not available in the record.
General: over-dispersion occurs when observed variability exceeds what a simple statistical model assumes. If present, it can make standard errors too small and intervals too narrow unless the analysis accounts for the extra variability. Whether over-dispersion is relevant depends on the outcome and model. Since no analysis model or outcome data are reported for this study, there is no basis to assess over-dispersion in its results.
What is the role of sample-size planning?
General: a sample-size calculation is a planning exercise based on assumptions about the outcome, target effect, variability, significance level, and desired power. Such a calculation does not establish that a study actually achieved a specified power, and it does not replace observed outcome data. The registry summary gives planned enrollment for the two study parts, but the formal sample-size justification and its assumptions are not reported in the registry record. The record also does not report an analysis that would support a claim of observed power.
Statistical interpretation is therefore constrained at an earlier stage than choosing among models or testing hypotheses: the outcome data and analysis are missing. No model-based estimate, hypothesis test, interval, or dose-selection result can be reconstructed from the registry record. General statistical concepts can clarify what such results would mean, but they cannot fill in the absent trial findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary dose-finding outcome and secondary outcomes covering objective response, overall survival, and the proportion alive at one year. Its brief summary also describes monitoring prostate-specific antigen and objective tumor response. Evaluating several outcomes creates a general multiplicity issue: the more questions examined, the greater the chance that at least one apparent finding may arise by chance when formal significance tests are used. Whether that issue was addressed depends on a prespecified analysis plan, including which outcomes were confirmatory and whether any adjustment or hierarchy was planned. Such a plan is not reported in the registry record.
The registry lists no statistical analyses. It provides no p-values, estimates, confidence intervals, or multiplicity adjustment. It is therefore not possible to determine how the outcomes would have been analyzed or how the study intended to control error across multiple questions. The outcome list alone does not establish that each outcome was formally tested.
Missing-data procedures and analysis populations are also not reported in the registry record. There is no account of participants included in each endpoint analysis, missing assessments, withdrawals, censoring, or the handling of incomplete follow-up. The registry says the principal investigator had left, contact attempts were unsuccessful, Columbia would not have access to the data, and the data would not be analyzed. This prevents assessment of whether missing observations could have affected any result.
General statistical context: an analysis population should be defined in advance because choices about who is included can affect estimates and their interpretation. Survival analyses additionally rely on information about follow-up and censoring. Without population definitions and participant-level outcome status, these features cannot be evaluated. The zero entries in the adverse-event record do not resolve these gaps or establish complete safety follow-up.
11. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase I/II study of bevacizumab, erlotinib, docetaxel, and prednisone was planned for patients with hormone refractory prostate cancer, that it was designed as a single-group study, and that it was terminated. It records enrollment of 4 participants. It also states that the study data would not be analyzed because the principal investigator had left the institution and the data would not be available to Columbia.
These registry entries do not establish what happened to the participants’ health or what outcomes they experienced. The record does not report the maximum tolerated dose, tumor response, prostate-specific antigen findings, survival outcomes, or analyzed safety results. The intended endpoint and outcome list describe questions the study set out to address; they are not evidence that those questions were answered.
The zero values in the adverse-event entries do not show that the regimen caused no adverse events. In the absence of a documented analysis and information about ascertainment, those entries cannot support that interpretation. Likewise, no reported result should not be treated as a null result: a null finding would require analyzed data that did not show evidence of an effect under a defined method. That is different from having no analyzed result available.
The study’s single-group design also limits what its results could establish even if outcomes had been reported. General: observed changes in one group do not alone identify what would have happened under a different treatment or no study treatment. A randomized comparator can support a more direct treatment contrast, but none is described in this record.
The sound interpretation is narrow: the registry documents the study’s objectives and design, a recorded enrollment of 4, and the absence of an analysis. It does not permit conclusions about treatment benefit, lack of benefit, dose tolerance, or the frequency of harm. The intended questions remain unanswered in the posted record.
12. Why This Trial Matters Statistically
This trial is statistically notable because it illustrates the difference between a registered research question and an interpretable result. The record describes a dose-finding objective, planned Phase II outcomes, and a single-group design, but reports no analyzed endpoint findings. For readers, the distinction matters: a clearly stated endpoint does not itself provide evidence about that endpoint.
The record also contrasts planned enrollment with recorded enrollment. The brief summary describes 18 participants in the first part and an additional 37 in the second, while the registry lists enrollment of 4. These figures describe different aspects of the record and should not be conflated. The record does not explain the difference, so it cannot support an account of why enrollment was limited or whether one or both planned parts were conducted.
The primary outcome was a dose-tolerance measure, whereas the secondary outcomes concerned tumor response and survival. These questions require different summaries and different follow-up information. A dose selected from safety observations is not interchangeable with evidence of clinical activity, and the planned activity outcomes cannot be inferred from a dose-finding objective. No findings for either kind of question are posted.
General statistical lesson: transparency about design, outcome definitions, participant flow, missing data, and analysis is essential for interpreting clinical research. When those elements are unavailable, a reader must distinguish documented plans from observed findings and avoid treating empty or zero-coded entries as affirmative evidence. This record makes that distinction especially important because it explicitly states that the data would not be analyzed.
The record therefore matters as an example of the limits of registry information when outcome data and analysis are unavailable. Its design can be described, but its treatment effects cannot be estimated from the information reported.
13. 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 central limitation is that the registry does not report analyzed study outcomes. It states that the principal investigator left the institution, attempts to contact the investigator were unsuccessful, Columbia would not have access to the data, and the data would not be analyzed. There is no reported maximum tolerated dose, dose-specific toxicity summary, response estimate, survival result, or measure of uncertainty. This prevents statistical evaluation of the study’s stated objectives.
The recorded enrollment is 4, while the brief summary describes a planned Phase I enrollment of 18 and an additional 37 in Phase II. The registry does not explain the difference or state how many participants started, completed, or were assessed at each dose. The summary notes that counts of participants who started and completed were the only information available, but those counts are not reported in the registry text. Enrollment alone cannot establish the number contributing to any particular endpoint.
The record gives no reason for termination and does not report whether the Phase II part began. It also lacks the eligibility criteria, participant characteristics, complete dose-escalation rules, toxicity definitions, analysis populations, missing-data procedures, follow-up details, and statistical analysis plan. These omissions limit assessment of both the intended design and the representativeness or completeness of any potential observations.
The adverse-event entries list zero participants at risk, zero affected, and zero deaths, but the record does not explain the completeness or derivation of those entries. Given the explicit statement that data would not be analyzed, these values cannot establish the absence of adverse events. Finally, the single-group design would not support a randomized comparison even if outcomes were available. Taken together, these limitations leave the safety, dose-tolerance, and activity questions unresolved.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Study of Bevacizumab and Erlotinib for Patients With Hormone Refractory Prostate Cancer — NCT00996502.
- Registry record last updated 2019-03-27; status last verified 2019-03.
- Results first posted 2016-03-25.
- 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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17. Record Summary
The registry describes a Phase I/II, single-group study of bevacizumab, erlotinib, docetaxel, and prednisone for hormone refractory prostate cancer. The study aimed to identify the maximum tolerated dose of docetaxel after three 21-day cycles and to evaluate activity outcomes. The brief summary describes planned enrollment of 18 participants in Phase I and an additional 37 in Phase II; the registry records enrollment of 4.
The study began in 2006-07, has a primary completion date of 2010-03, and is listed as terminated. Allocation is not applicable and masking is none. The registry lists objective response, overall survival, and the proportion alive at one year among secondary outcomes, but reports no statistical analyses or outcome estimates.
The record states that the principal investigator had left the institution, contact attempts were unsuccessful, Columbia would not have access to the data, and the data would not be analyzed. Consequently, the primary endpoint and the planned safety and activity questions have no reported result in the registry record.