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 Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder (NCT00085410), a na phase 2 study. The primary outcome is Objective Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00085410 |
| Phase | Phase 2 |
| Condition | Adenocarcinoma of the Extrahepatic Bile Duct, Adenocarcinoma of the Gallbladder, Advanced Adult Primary Liver Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with unresectable locally advanced or metastatic adenocarcinoma of the bile duct or gallbladder. The registry record also lists conditions involving extrahepatic bile duct and gallbladder cancer. It does not report detailed eligibility criteria, such as the requirements used to determine whether a patient could enroll, or how the study defined locally advanced disease.
Intervention
The intervention was bortezomib as first-line systemic therapy. In Arm I, patients received bortezomib intravenously over 3-5 seconds on days 1, 4, 8, and 11. The registry record does not state a dose or specify the length of a treatment cycle.
Comparator
There was no comparator group. The study is recorded as a single-group trial with allocation listed as not applicable and no masking. Its design therefore does not support a direct randomized comparison between bortezomib and another treatment or a control condition.
Primary question
The primary endpoint was objective response rate, assessed by best radiologic response according to RECIST 1.0 using computed tomography or magnetic resonance imaging. The endpoint was defined for the per-protocol population over up to 1 year. The registry record does not report the response count or response rate, so it cannot establish from the posted results how many patients met the response criteria.
3. Trial Design
This was a phase II, single-group study of bortezomib in patients with unresectable or metastatic adenocarcinoma of the bile duct or gallbladder. The registry record lists enrollment as 20. A single-group design assigns no separate control arm for comparison; allocation is recorded as not applicable. Masking is listed as none, so the record does not describe a blinded treatment assignment.
Arm I received bortezomib intravenously over 3-5 seconds on days 1, 4, 8, and 11. The study summary describes the treatment as first-line systemic therapy. A dose, cycle length, treatment duration rules, and criteria for stopping treatment are not reported in the registry record.
The recorded start was 2004-01, and primary completion was 2008-08. The trial status is terminated. The reason for termination and whether the study ended as initially planned are not reported in the registry record; termination alone does not explain why the trial stopped.
The primary outcome was objective response rate, based on best response by radiologic assessment under RECIST 1.0, using computed tomography or magnetic resonance imaging. The outcome population is identified as per protocol, and the timeframe is up to 1 year. Secondary outcomes included time to disease progression and overall survival, along with analyses relating proteasome inhibition and molecular markers to clinical outcomes or treatment-related changes. The registry record lists 11 outcome measures, but does not report results for the primary endpoint in the registry record for interpretation.
The sponsor is the National Cancer Institute. The registry record does not report a control group, randomization, or a detailed statistical analysis plan. These design features limit what can be concluded about comparative treatment effects.
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: Twenty individuals were enrolled in this study over a four year period.
Overall Study
| Stage | Arm I |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Per protocol
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 | Arm I |
|---|---|---|
| Participants analysed | 20 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 13 |
| Age, Categorical: >=65 years | Participants | 7 |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 11 |
| Region of Enrollment: United States | participants | 20 |
| Site of Primary Tumor: Gallbladder | participants | 6 |
| Site of Primary Tumor: Intrahepatic or extrahepatic cholangiocarcinoma | participants | 14 |
| Site of Metastases: Liver | participants | 14 |
| Site of Metastases: Lymph nodes | participants | 7 |
| Site of Metastases: Lung | participants | 5 |
| Site of Metastases: Other | participants | 2 |
| Eastern Cooperative Oncology Group Performance Status: Grade 0 | participants | 7 |
| Eastern Cooperative Oncology Group Performance Status: Grade 1 | participants | 13 |
| Previous Treatment: None | participants | 10 |
| Previous Treatment: Chemotherapy only | participants | 4 |
| Previous Treatment: Chemotherapy/radiation therapy | participants | 5 |
| Previous Treatment: Other | participants | 1 |
| Previous Surgery: Yes: Cholecystectomy | participants | 4 |
| Previous Surgery: Yes: Liver section | participants | 1 |
| Previous Surgery: No | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response Rate, measured over Up to 1 year.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
Objective response rate (ORR) is the proportion or count of patients whose tumors meet prespecified criteria for an objective reduction or disappearance on assessment. In this trial, the registry defines the endpoint by best response on radiologic assessment using computed tomography or magnetic resonance imaging, according to RECIST 1.0. It identifies participants as the unit and the per-protocol population as the analysis population, with assessment over up to 1 year.
As a general statistical concept, an objective response endpoint turns imaging assessments into a categorical outcome: each assessed participant is classified according to whether the criteria for response were met. This can provide a direct description of tumor response during a study. The endpoint does not by itself describe how long a response lasts, whether disease later progresses, or how survival compares with another treatment. Those questions require other outcomes and appropriate follow-up.
The response count and response rate are not reported in the registry record details available for this analysis. Nor are the per-protocol denominator, response categories, or uncertainty interval reported. Consequently, the endpoint definition can be described, but the magnitude and precision of the trial’s primary result cannot be assessed from the registry record. A stated endpoint should not be mistaken for a reported endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies objective response rate as the primary outcome, but the registry entries do not include the number of participants who responded or the response rate. There is therefore no primary efficacy estimate to interpret. The absence of a reported response result is not evidence that no responses occurred; it means the primary result is not reported in the registry record.
Enrollment is listed as 20, while the primary endpoint population is described as per protocol. These are not necessarily interchangeable analysis populations. The number assessed for response and the reasons for any exclusions or missing assessments are not reported in the registry record. Without those details, the denominator behind an ORR estimate cannot be established from the registry entries.
The single-group design can describe outcomes among participants treated in the study, if those outcomes are reported. It cannot provide a randomized comparison against another treatment or control. Any changes over time in an uncontrolled group may reflect factors beyond the intervention, so the design does not isolate a comparative treatment effect. No masking is recorded, which is relevant context for a study whose primary outcome depends on radiologic assessment; the registry record does not describe any independent or blinded review process.
The trial is listed as terminated, but the reason for termination is not reported in the registry record. The status should not be interpreted as evidence for or against efficacy, safety, or feasibility. Likewise, the record’s phase designation does not replace the need to examine the actual outcome estimates and their uncertainty.
The registry lists serious adverse-event figures for Arm I: 4 participants affected among 20 at risk. It also lists 20 participants affected among 20 at risk for other adverse events. Four serious-event terms are each listed at 5.0%. These safety counts describe the recorded group; they do not establish that events were caused by bortezomib or enable comparison with another treatment. The deaths field is not reported in the registry record.
Overall, the registry entries establish the trial’s design, endpoint definition, status, and selected safety counts, but do not provide the primary response result or its precision. Conclusions about the size of an efficacy effect are therefore not supported by these posted results.
9. Statistical Methods Explained
The registry describes a single-group phase II study, with no masking and allocation listed as not applicable. In a single-group study, participants receive the study intervention without a separate randomized control arm. This design can document outcomes in the treated group, but does not estimate a randomized difference between treatment strategies. General statistical interpretation of a treatment effect must account for that limitation.
What does the primary endpoint count?
The primary endpoint is objective response rate, reported in terms of participants. Its definition uses best radiologic response under RECIST 1.0, based on computed tomography or magnetic resonance imaging, and the analysis population is per protocol. In general, this is a binary-outcome framework: a participant is classified as meeting or not meeting the response definition. The registry record does not report the response count, response rate, or per-protocol denominator in the registry record.
A count and a rate answer different descriptive questions. A count gives the number classified as responders, while a rate relates that count to the participants evaluated under the endpoint definition. Neither alone communicates precision. A confidence interval is a range of values compatible with the observed data under a specified statistical method; it helps convey how uncertain an estimate is. No confidence interval for the primary endpoint is reported in the registry record.
What can a single-group result establish?
In general, a response rate in a single treated group describes observed response under that study’s eligibility rules, treatment procedures, assessment schedule, and analysis population. It does not by itself show how the same participants would have fared under a different treatment. Without a concurrent randomized comparison, differences from outcomes in another population or another study may reflect differences in participants, measurement, follow-up, or care as well as treatment.
The study is recorded as unmasked. For an imaging-based endpoint, knowledge of treatment assignment can be relevant to assessment processes. The registry record does not report whether images underwent independent review, whether assessors were blinded, or how disagreements were resolved. These details should not be assumed.
How should the endpoint population be read?
The registry identifies the primary outcome population as per protocol, rather than describing it simply as everyone enrolled. In general, a per-protocol analysis focuses on participants who meet specified criteria for following the study regimen or protocol. The particular criteria used in this trial, the number included in the analysis, and the handling of participants without assessable imaging are not reported in the registry record. That omission matters because endpoint estimates depend on who is included and how missing assessments are handled.
Enrollment is recorded as 20, but this does not establish the endpoint denominator. Participants can be excluded from a per-protocol analysis or lack an evaluable assessment; whether either occurred is not reported in the registry record. No analysis should silently substitute enrollment for the response denominator.
What does the sample-size illustration mean?
General sample-size planning estimates the amount of information that may be needed to detect a specified effect under stated assumptions. The planning description associated with the study material says the illustration uses 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. It also states that time-to-event illustrations count total events and other illustrations count participants per arm.
Those assumptions describe a planning illustration, not the trial’s own design or an observed-power calculation. This registry study is single-group, and no two-arm allocation is recorded for it. The registry record does not report a protocol sample-size justification or the assumptions used by investigators in designing the trial. No planning sample-size output is stated in the registry entries, so no numerical target can be interpreted. In general, a planning estimate is conditional on its assumptions and should not be read as proof that a study was adequately powered or that a finding is reliable.
What statistical plan is documented?
The primary endpoint definition and analysis population are recorded, but a detailed statistical plan is not reported in the registry record. The specific method for estimating ORR, any confidence-interval method, any hypothesis test, and any planned subgroup analyses are not reported. These omissions do not prove that investigators performed no such analyses; they mean the registry information does not describe them.
The registry lists 11 outcome measures and zero analyses. Those entries do not establish that no analysis was conducted outside the registry record. They do mean that statistical estimates, uncertainty measures, and analysis details cannot be reconstructed from the listed details. General statistical interpretation should therefore distinguish the endpoint definition from numerical results and should not infer an unstated analysis method.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures, including objective response rate, time to disease progression, overall survival, and outcomes concerning proteasome inhibition and molecular markers. Considering multiple outcomes can raise multiplicity concerns: as a general statistical concept, testing many hypotheses can increase the chance of at least one apparently unusual result if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity adjustment, an outcome hierarchy, or a plan for interpreting multiple tests. This does not establish that no such plan existed; it is not reported in the registry record.
The record identifies the primary outcome as ORR and the analysis population as per protocol. It does not report the number analyzed, the response denominator, or how participants with missing or unevaluable imaging were handled. The eligibility rules defining the per-protocol population and any imputation or sensitivity analyses are also not reported in the registry record. These details are important because the analysis population and handling of missing outcomes can affect an estimate.
The registry lists zero analyses. That means analyses are not listed in the registry entries used here, not necessarily that no analyses were performed. A detailed statistical analysis plan, including rules for missing data and multiplicity, is not reported in the registry record. As a result, the available information does not support a judgment about how these issues were managed.
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 |
|---|---|---|---|
| Arm I | 4 | 20 | 20.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm I | 20 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm I |
|---|---|---|
| aseptic vasculitis | Nervous system disorders | 1 of 20 |
| cerebrovascular accident | Vascular disorders | 1 of 20 |
| meningitis | Nervous system disorders | 1 of 20 |
| renal insufficiency | Renal and urinary disorders | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm I |
|---|---|---|
| Fatigue | General disorders | 18 of 20 |
| Anemia | Blood and lymphatic system disorders | 15 of 20 |
| thrombocytopenia | Skin and subcutaneous tissue disorders | 14 of 20 |
| Nausea | Gastrointestinal disorders | 11 of 20 |
| Pain (all sites) | General disorders | 9 of 20 |
| Elevated AST/ALT | Metabolism and nutrition disorders | 7 of 20 |
| Vomiting | Gastrointestinal disorders | 7 of 20 |
| Sensory neuropathy | Nervous system disorders | 6 of 20 |
| Leukopenia | Blood and lymphatic system disorders | 5 of 20 |
| Neutropenia | Infections and infestations | 5 of 20 |
Serious events with the highest arm-level rate: aseptic vasculitis (5.0%), cerebrovascular accident (5.0%), meningitis (5.0%), renal insufficiency (5.0%).
For Arm I, the registry records 20 participants at risk for serious adverse events and 4 participants affected. For other adverse events, it records 20 at risk and 20 affected. These are participant counts, not a comparative estimate against another group. The registry also lists aseptic vasculitis, cerebrovascular accident, meningitis, and renal insufficiency as serious-event terms, each at 5.0%.
The event-term percentages should be read as registry-listed values. They do not indicate how many separate participants experienced each term, whether a participant experienced more than one term, or the timing or duration of events. The counts for serious and other adverse events are presented separately and should not be added together to infer a total number of participants affected.
Safety counts alone do not establish causation. The registry record does not report a comparison group or provide enough information to determine whether each event was attributed to treatment. The deaths field is not reported in the registry record. These figures describe recorded adverse events in the study group; they are not a complete account of the safety profile or a basis for comparing treatments.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, single-group study evaluated bortezomib for unresectable or metastatic adenocarcinoma of the bile duct or gallbladder, with objective response rate as the primary endpoint. It defines response by best radiologic assessment under RECIST 1.0 and identifies the per-protocol population and a timeframe of up to 1 year. It also records selected adverse-event counts and lists the study as terminated.
The primary response result itself is not reported in the registry record details available for this analysis. There is no response count, response rate, confidence interval, or primary endpoint test to interpret. This means the magnitude and precision of the response outcome cannot be established from these registry entries. It does not mean the trial observed no responses, nor does the missing result imply a particular clinical effect.
The single-group design has no randomized comparator, so even a reported response rate would describe outcomes in the study group rather than establish how outcomes compare with another treatment. The record also lists no masking. It does not report details of imaging review that would clarify how outcome assessment was protected from potential assessment bias.
The safety entries indicate that adverse events were recorded among participants in Arm I, including 4 affected by serious adverse events out of 20 at risk and 20 affected by other adverse events out of 20 at risk. Those counts do not establish causality, and the listed terms do not provide a comparison with another group. The record does not report the reason for termination, missing-outcome handling, or detailed statistical methods.
Accordingly, the posted information supports a description of the design, endpoint definition, and selected safety reporting. It does not support a numerical conclusion about objective response or a comparative conclusion about treatment effects. The distinction between a trial’s stated question and its reported results is essential when interpreting a registry entry.
13. Why This Trial Matters Statistically
This trial illustrates why registry interpretation begins by separating design information from outcome evidence. The record specifies a primary endpoint and how it was to be assessed, but the response result is not reported in the registry record for interpretation. A well-defined endpoint is not itself a result. Without the estimate, denominator, and measure of uncertainty, readers cannot evaluate the size or precision of the primary finding.
The single-group design is also central to the statistical meaning of any outcome. A treated-group response rate, if reported, could describe what happened among participants included in the analysis. It could not by itself provide a randomized treatment comparison. This distinction matters whenever a study’s stated objective uses language about how well an intervention works: the design determines which effects can be estimated and how strongly they can be attributed to treatment.
The per-protocol designation highlights another important issue. Enrollment and endpoint analysis populations may differ, and the registry record does not state the denominator or criteria used for the primary analysis. In general, readers need to know who was analyzed and how missing assessments were handled to judge the validity and applicability of a binary endpoint.
Finally, the record lists multiple outcomes, selected safety counts, and a terminated status, but does not document a detailed statistical plan or a reason for termination. Those details should be reported as context, not treated as evidence of an unreported result. The trial is a useful example of how design, endpoint specification, analysis population, and reporting completeness jointly constrain statistical interpretation.
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 efficacy is that the objective response result is not reported in the registry record details. The response count, rate, denominator, and uncertainty interval are absent, so the magnitude and precision of the primary endpoint cannot be assessed. The per-protocol population is named, but its size and criteria are not reported.
The single-group design provides no randomized comparator. Consequently, the record cannot support a direct comparative estimate against another treatment or control. The study is also recorded as unmasked. Whether imaging was reviewed independently or under blinded conditions is not reported in the registry record.
The registry lists the trial as terminated, but does not report why it was terminated or whether that status affected the planned conduct or reporting. A detailed statistical analysis plan, sample-size justification, missing-data approach, and multiplicity strategy are not reported in the registry record. The registry entries therefore do not establish how analyses were specified or how incomplete assessments were handled.
Safety information is limited to the listed participant counts and serious-event terms. The deaths field is not reported in the registry record, and the registry entries do not provide event timing, duration, attribution, or a comparator. The listed event terms should not be treated as exhaustive or as proof of treatment causation. These limitations restrict both efficacy and safety interpretation to the information explicitly recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder — NCT00085410.
- Registry record last updated 2017-07-02; status last verified 2017-06.
- Results first posted 2017-06-14.
- 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
The record describes a phase II, single-group, unmasked study sponsored by the National Cancer Institute. It lists enrollment as 20, a start of 2004-01, primary completion in 2008-08, and status as terminated. Participants in Arm I received bortezomib intravenously over 3-5 seconds on days 1, 4, 8, and 11.
The primary endpoint was objective response rate, assessed by best radiologic response under RECIST 1.0 using computed tomography or magnetic resonance imaging. The outcome population was per protocol and the timeframe was up to 1 year. The primary response result is not reported in the registry record details available for interpretation.
The record lists 11 outcome measures and zero analyses. For Arm I, it records 4 participants affected by serious adverse events among 20 at risk, and 20 affected by other adverse events among 20 at risk. Four serious-event terms are listed at 5.0% each. The reason for termination and the deaths field are not reported in the registry record.