← Clinical Trials
Biliary Tract Cancer Phase 2 Binary Endpoint NCT01308840

Gemcitabine, Oxaliplatin and Panitumumab in Kras/B-raf Wild-Type Biliary Track and Gallbladder Cancer: Complete Statistical Analysis

This phase II, single-group study examined gemcitabine, oxaliplatin, and panitumumab in people with KRAS/BRAF wild-type, advanced biliary tract or gallbladder cancer. The registry record identifies tumor response as the primary outcome but does not report the response result.

Trial start: 2010-12  ·  Enrollment: 31  ·  Sponsor: University of Rochester
Scope of this record

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 Gemcitabine, Oxaliplatin and Panitumumab in Kras/B-raf Wild-Type Biliary Track and Gallbladder Cancer (NCT01308840), a na phase 2 study. The primary outcome is The Number of Participants With Response to GEMOX-Panitumumab (GEMOX-P) in Chemotherapy naïve KRAS/ BRAF Wild Type Stage IV Biliary Tract Cancer Using the Response Evaluation Criteria In Solid Tumors (RECIST) Criteria..

31
Enrollment
Phase 2
n/a
Arms
In the primary outcome
n/a
Effect
No re-analysis shown
n/a
95% CI
See limitations
FeatureRegistry value
ClinicalTrials.gov identifierNCT01308840
PhasePhase 2
ConditionBiliary Tract Cancer, Gallbladder Cancer
AllocationNot applicable (single group)
Design modelSingle Group
MaskingNone (open label)
Enrollment31
Arms in the primary outcomen/a
Lead sponsorUniversity of Rochester
Results postedYes

2. Clinical Question

Population

People described as having chemotherapy-naïve, KRAS/BRAF wild-type, Stage IV biliary tract or gallbladder cancer. The study description refers to unresectable or metastatic disease. The registry record does not report further eligibility details or the characteristics of participants enrolled.

Intervention

Gemcitabine, oxaliplatin, and panitumumab given together. The listed regimen gives each drug on days 1 and 15 of a 28-day cycle.

Comparator

There is no separate comparator group in this single-group study. The registry record does not describe a randomized allocation or a like-for-like control group.

Primary question

How many participants had a tumor response by the end of cycle 2, assessed using RECIST criteria? The registry record names this as the primary outcome but does not report the observed response count or a corresponding estimate of uncertainty.

The central statistical question is descriptive: among participants treated in this study, what proportion or count met the response definition at the specified assessment? The primary outcome is recorded as a number of participants, rather than as a continuous measurement or time-to-event summary. Although a count can describe what happened in the enrolled group, it does not by itself establish how response would compare with another treatment or with an untreated group.

The study also aimed to examine progression-free survival, overall survival, and adverse events. These outcomes address different aspects of the observed experience: time until progression or death, time until death, and harms recorded during treatment. The registry record names these secondary outcomes but does not provide their results in the material described. The question therefore cannot be extended to those outcomes on the basis of the record alone.

The population is narrowly characterized by tumor type, stage, prior chemotherapy status, and KRAS/BRAF status. Whether the enrolled participants fully represented that intended population, and how many had each cancer type, are not reported in the registry record. Those details matter when judging how broadly descriptive findings might apply.

3. Trial Design

This was a phase II, single-group study of gemcitabine, oxaliplatin, and panitumumab. The registry record reports an enrollment of 31. It identifies University of Rochester as the sponsor, gives a start date of 2010-12, a primary completion date of 2013-01, and a status of completed.

The study did not use a concurrent control arm: the design is recorded as single group, and allocation is listed as not applicable. Masking is recorded as none. Consequently, the design describes outcomes among people receiving the regimen, not a randomized comparison between treatments. A change or response observed during follow-up cannot, by itself, isolate the contribution of any one of the three drugs or distinguish treatment effects from other explanations.

The listed regimen gives panitumumab 6mg/kg, gemcitabine 1000mg/m2, and oxaliplatin 85mg/m2 on days 1 and 15 of every 28-day cycle. The registry description specifies tumor measurement at the end of cycle 2, using the same imaging modality used in the pretreatment evaluation. It describes CT scans of the chest, abdomen, and pelvis for pretreatment and end-of-cycle-2 assessments, and CT scans of those areas every 8 weeks in subsequent cycles.

The primary outcome is the number of participants with response according to RECIST criteria, with the stated assessment at the end of cycle 2. The named secondary outcomes are median progression-free survival, median overall survival, and the number of participants who experience an adverse event. The registry record lists four outcome measures overall but does not report the fourth measure in the available outcome descriptions.

The record does not report the planned sample-size justification, a detailed statistical analysis plan, interim analyses, or detailed criteria for analysis populations. Assumptions attached to planning illustrations describe a hypothetical two-arm calculation; they are not a description of the single-group study's design or evidence of observed power.

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: 5 subjects were not eligible to enroll. 2 participants did not receive the intervention.

Overall Study

StagePanitumumab
STARTED31
COMPLETED31
NOT COMPLETED0

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.

CharacteristicUnitPanitumumab
Participants analysed31
Age, Continuousyears61 (36 to 74)
Sex: Female, Male: FemaleParticipants14
Sex: Female, Male: MaleParticipants17
Region of Enrollment: United Statesparticipants31
Eastern Cooperative Oncology Group (ECOG) Performance status: 0participants10
Eastern Cooperative Oncology Group (ECOG) Performance status: 1participants21
Extent of disease: locally advancedparticipants2
Extent of disease: metastaticparticipants29
primary tumor site: intrahepatic cholangiocarcinomaparticipants25
primary tumor site: gallbladderparticipants3
primary tumor site: extrahepatic cholantiocarcinomaparticipants3
metastases: lymph nodesparticipants24
metastases: lungparticipants8
metastases: boneparticipants4
metastases: omentum/peritonealparticipants4
metastases: adrenalparticipants3
metastases: pelvic soft tissueparticipants1

6. Primary Endpoint

The registry lists the primary outcome as The Number of Participants With Response to GEMOX-Panitumumab (GEMOX-P) in Chemotherapy naïve KRAS/ BRAF Wild Type Stage IV Biliary Tract Cancer Using the Response Evaluation Criteria In Solid Tumors (RECIST) Criteria., measured over end of cycle 2 of treatment.

ElementRegistry entry
Result typeNumber
Measure of spreadnot applicable
Unitparticipants
Endpoint classificationBinary Endpoint

The primary endpoint is the number of participants with a tumor response to the combination by the end of cycle 2 of treatment. Response is assessed using the Response Evaluation Criteria in Solid Tumors, or RECIST. The registry record describes tumor measurement using the same imaging modality as the pretreatment evaluation, with CT scans of the chest, abdomen, and pelvis for pretreatment and end-of-cycle-2 assessments.

In general, a response endpoint applies predefined criteria to measurements of disease and classifies whether a participant meets the response definition. A count of responders is clinically interpretable as a description of how many participants met that definition at the specified assessment. It is not the same as a measure of how long disease control lasts, nor does it summarize survival. The record separately names progression-free and overall survival as secondary outcomes.

Using a specified assessment time and a recognized response framework helps make the endpoint more reproducible than an informal judgment of improvement. Repeated imaging is also described for subsequent cycles, with chest, abdomen, and pelvis CT every 8 weeks. However, the primary endpoint is tied to the end-of-cycle-2 assessment, so later imaging does not change the stated primary time point.

The registry record does not report the observed number of participants with response, the response categories used in the final analysis, or an uncertainty interval. Therefore, the endpoint's definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

Reported as posted, not recalculated. Not a randomized comparison (allocation: NA); arms are not a like-for-like control comparison. A result is recalculated only when the posted data support a clean two-arm comparison, so no result is shown beyond what the sponsor posted.

8. Statistical Interpretation

Clinical Biostats interpretation

The record describes a prospective treatment study with one group and an enrollment of 31. Its main outcome is a response count at the end of cycle 2, but the posted results do not give that count. As a result, the primary outcome cannot be numerically interpreted from the record described: there is no reported response estimate to characterize, and no confidence interval or other measure of precision is reported.

The absence of a reported primary result should not be mistaken for a response count of zero. The endpoint is named, but its result is not reported in the registry record. Similarly, the record's completion status does not establish what the outcome was. A completed study can have outcome definitions and participant counts recorded without presenting the numerical findings needed to assess the endpoint.

Even if a response count were available, a single-group result would describe the participants observed under this regimen. Without a concurrent control group, it would not directly estimate a difference in response compared with another treatment. It also would not identify the separate contribution of panitumumab, gemcitabine, or oxaliplatin. Those are design limitations, not statements about whether the regimen did or did not produce responses.

The secondary outcomes named in the registry are median progression-free survival, median overall survival, and adverse events. The record does not report numerical results for the survival outcomes. For adverse events, it reports 31 participants at risk and 31 affected for other adverse events, and 31 at risk and 0 affected for serious adverse events. Those counts describe the registry entries, but the record does not give event definitions, grades, attribution, or participant-level detail. It does not list serious adverse-event terms, and deaths are not reported in the adverse-event entry.

In general, statistical precision is conveyed by an uncertainty interval around an estimate. A confidence interval indicates a range of values compatible with the data and analysis under the method's assumptions; it does not eliminate uncertainty or establish that every value in the interval is equally plausible. No interval for the primary response endpoint is reported, so the degree of statistical precision cannot be assessed from this record.

Planning illustrations associated with the record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects expressed as fractions of an observed effect. They are hypothetical planning calculations rather than the design of this single-group trial. They are not observed power, and they do not fill in the missing response result. The observed effect and the numerical planning rows are not reported in the registry record described.

The most defensible interpretation is therefore limited: the registry records the design, regimen, endpoint definition, and some adverse-event counts, but it does not report the primary response result or the survival estimates. No treatment comparison or efficacy conclusion can be drawn from those omissions.

9. Statistical Methods Explained

Statistical methods describe how outcomes are defined, summarized, and compared, and how uncertainty and missing observations are handled. For this study, the registry record supplies some design and outcome definitions but does not report a full statistical analysis plan or numerical primary outcome findings. The explanations below distinguish general statistical concepts from details recorded for this trial.

What does a single-group design estimate?

For a binary outcome such as whether a participant met response criteria, a single-group study can report a count of participants meeting the definition among those assessed. A proportion is often used in general to express a binary outcome relative to the number assessed, but no response proportion is reported for this study. A single-group estimate describes the observed group; it does not provide a randomized between-group treatment contrast. Without a control group, differences from an external benchmark can also be affected by differences in populations, assessment, follow-up, or other aspects of care.

The record identifies this study as single group, with allocation not applicable and masking none. It does not report a formal comparison group or a randomized allocation procedure. Thus, a comparative treatment effect cannot be calculated from the recorded design information.

What does the response endpoint represent?

The primary measure is a participant count based on tumor response under RECIST criteria at the end of cycle 2. In general, binary endpoints classify each participant according to whether a prespecified condition is met. A clear definition and assessment time help specify what counts as an event. For this endpoint, the record describes pretreatment imaging and an assessment at the end of cycle 2, using the same imaging modality for tumor measurement and CT scans of the chest, abdomen, and pelvis. It does not report the final response count or the response classifications used in the posted results.

Measurement rules matter because differences in imaging, timing, or interpretation can affect endpoint classification. The record gives a schedule and imaging description, but it does not report details such as independent review, assessor blinding, or procedures for resolving disagreement. Those procedures are not reported in the registry record and should not be assumed.

How should uncertainty be understood?

General statistical explanation: an estimate from a limited group is subject to sampling variability. A confidence interval is one way to express that uncertainty. Its width depends on the amount and variability of information and on the method used. It does not account automatically for every source of bias, and it does not turn an uncontrolled observation into a randomized comparison. No confidence interval for response is reported in the registry record, so the precision of that outcome cannot be assessed.

For a binary outcome, analysts may use methods based on a binomial model or approximations, depending on the analysis plan and data. The registry record does not state which interval or test, if any, was planned for the response endpoint. No particular method should therefore be attributed to the study.

What do the planning assumptions mean?

The planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They refer to detecting a stated fraction of an observed effect. The assumptions also distinguish calculations for time-to-event outcomes, which use a total number of events, from other calculations, which use participants per arm. These are assumptions for planning illustrations; they do not describe the actual single-group design, and they are not observed power. The numerical sample-size illustrations and the observed effect are not reported in the registry record described.

In general, a sample-size calculation depends on assumptions about the outcome, effect to detect, variability or event frequency, error rates, allocation, and analysis method. If those assumptions do not reflect the eventual study or target question, the calculation may not answer the same question as the observed data. The trial's own sample-size justification is not reported in the registry record.

Why do event definitions and exposure matter for safety?

Safety counts depend on what qualifies as an event, how severity is graded, how events are attributed, and which participants are included in the risk set. The registry lists 31 at risk and 0 affected for serious adverse events, and 31 at risk and 31 affected for other adverse events. The definitions and detailed event-level breakdown are not reported in the registry record. Counts alone do not show how long participants were observed or how many events each participant experienced.

In general, an event count and a count of participants with at least one event are different summaries. A participant count avoids treating repeated events in one person as separate people, while a total event count captures recurrence. The registry wording describes numbers of participants affected, but additional details needed to interpret recurrence, severity, and timing are not reported.

Overall, the available method information establishes the study's single-group structure, response assessment, and some safety counts. It does not establish which statistical tests, confidence-interval methods, missing-data procedures, or analysis populations were used. Those items are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record names the response count as the primary outcome and lists median progression-free survival, median overall survival, and the number of participants who experience an adverse event as secondary outcomes. It also records four outcome measures overall, but the fourth measure is not identified in the outcome descriptions available. Numerical results for the response and survival outcomes are not reported in the registry record described.

Multiplicity arises when several outcomes or analyses are examined. In general, the more statistical questions addressed, the greater the opportunity for at least one apparently notable result to arise by chance if each is assessed separately. A statistical plan may specify which outcome is primary, how secondary outcomes are interpreted, and whether any adjustment is used. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether adjustment was planned. No claim about adjustment or its absence in the actual analysis can be made.

The record also does not report how missing endpoint assessments were handled, how many participants were missing an assessment, or which participants were included in each efficacy analysis. It does not specify an intention-to-treat, per-protocol, or other analysis population. Those details are not reported in the registry record. For an imaging-based response outcome, missing or unevaluable assessments can affect the analysis denominator and interpretation; general approaches include prespecified rules for classifying or excluding such observations, but no approach should be assumed for this study.

The listed enrollment is 31, while the adverse-event entries give 31 participants at risk. The record does not establish that all enrolled participants completed the primary response assessment or explain any differences between enrollment and outcome-specific populations. The analysis population, follow-up completeness, and handling of withdrawals are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

ArmParticipants with serious adverse eventsParticipants at riskPercentage
Panitumumab0310.0%

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

ArmParticipants affected of at risk
Panitumumab31 of 31

Most frequent non-serious adverse event terms

Event termOrgan systemPanitumumab
AnaemiaBlood and lymphatic system disorders26 of 31
FatigueGeneral disorders25 of 31
ThrombocytopeniaBlood and lymphatic system disorders24 of 31
NauseaGastrointestinal disorders23 of 31
neuropathyNervous system disorders21 of 31
HypomagnesemiaBlood and lymphatic system disorders21 of 31
rashSkin and subcutaneous tissue disorders20 of 31
elevated alkaline phosphataseHepatobiliary disorders20 of 31
LeukopeniaBlood and lymphatic system disorders19 of 31
diarrheaGastrointestinal disorders14 of 31
Do not overextend the safety comparison. Serious-adverse-event counts are safety observations, not efficacy outcomes, and should not be combined with the primary result into a single benefit-risk number.

The adverse-event entry reports 31 participants at risk for serious adverse events and 0 affected. For other adverse events, it reports 31 at risk and 31 affected. These are participant counts in the registry record, not a detailed account of event episodes, severity grades, timing, or causal attribution.

The record does not list serious adverse-event terms. That is distinct from a detailed narrative establishing which specific events were monitored or why no terms appear in the entry. Deaths are recorded as not reported in the adverse-event data. The record does not provide the number of events per participant or exposure time, so the counts do not describe recurrence or event rates over time.

In general, serious adverse events and other adverse events are different reporting categories. A count of participants with at least one event is also different from a count of all events: one participant may experience more than one event. The registry's counts can be read as the number of participants reported as affected in each category, but further interpretation requires event definitions, grading, attribution, and follow-up information. Those details are not reported in the registry record.

The safety counts should be interpreted as registry-reported observations, not as a complete characterization of tolerability or comparative risk. There is no separate control group for estimating a difference in harms.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a phase II, single-group study of gemcitabine, oxaliplatin, and panitumumab was completed, with an enrollment of 31. It specifies a primary response endpoint based on RECIST at the end of cycle 2 and describes imaging procedures. It also names progression-free survival, overall survival, and adverse events as secondary outcomes.

What the record does not establish is the primary outcome result. The number of participants with response and an estimate of its precision are not reported in the registry record described. Therefore, the study's response outcome cannot be summarized numerically or judged for precision from this information. The absence of a reported result is not evidence that no responses occurred.

More generally, a response observed in a single group is a description of that group under the study conditions. It is not a randomized estimate of the difference between this regimen and another treatment. The design also cannot separate the effects of the three drugs. These limitations apply regardless of the direction or size of any unreported result.

The safety entry reports 0 participants affected by serious adverse events among 31 at risk, and 31 affected by other adverse events among 31 at risk. Interpretation remains limited because event definitions, severity, attribution, timing, and counts of repeated events are not reported. The survival outcomes are named but their numerical results are not reported.

In general, results from a clinical study are most informative when estimates are accompanied by uncertainty, clear analysis populations, outcome definitions, and enough detail to assess follow-up and missing data. The registry record supplies some outcome definitions and design features but does not report several of these analytic details. It therefore supports a description of what was planned and some safety counts, but not a complete statistical assessment of response, survival, or comparative benefit and harm.

13. Why This Trial Matters Statistically

Statistically, this trial illustrates the distinction between an endpoint definition and an endpoint result. The registry identifies a specific response measure, assessment time, and imaging approach. Those details tell a reader what outcome the study intended to describe. They do not reveal how many participants met the response criteria; that result is not reported in the registry record.

The single-group design is also important. A treatment study can collect useful descriptive information without a randomized comparator, but the estimand is different: the observed outcome among participants in the study is not a controlled treatment contrast. This distinction helps prevent overinterpretation of a response count as evidence of comparative effect. The same point applies to safety counts, which lack a concurrent group for comparison.

The registry lists an enrollment of 31 and reports adverse-event counts for 31 participants at risk. Such counts provide a starting description, while precision and context depend on the endpoint result, definitions, analysis population, follow-up, and uncertainty measures. Several of those details are not reported in the registry record. For the primary response endpoint in particular, the missing numerical result prevents even a descriptive estimate of response frequency.

The planning assumptions further illustrate why design and sample-size calculations must be kept distinct. The stated hypothetical two-arm assumptions do not match the recorded single-group design, and planning calculations are not observed power. A planning illustration cannot substitute for a reported endpoint estimate or establish what the trial found.

These features make the record useful for understanding how study design, measurement, reporting, and inference fit together. A well-defined endpoint is necessary for interpretation, but complete outcome reporting and an appropriate comparison design are also needed to answer broader questions about treatment effects.

14. Limitations

The main limitation for statistical interpretation is that the primary response count is not reported in the registry record described. No estimate of response or uncertainty is available, and the numerical results for the named survival outcomes are also not reported. The record therefore does not support a complete account of the study's primary or survival findings.

The single-group design has no concurrent control arm, and allocation is recorded as not applicable. Masking is recorded as none. These features limit causal and comparative interpretation: observed outcomes cannot be attributed uniquely to the regimen or compared directly with another treatment within this study.

The record does not report participant characteristics beyond the intended disease and molecular-status description, nor does it give detailed eligibility criteria or outcome-specific analysis populations. It does not explain missing assessments, withdrawals, follow-up completeness, or how unevaluable imaging was handled. These omissions make it difficult to judge representativeness and the risk of bias in the outcome summaries.

For safety, the registry gives participant counts but not event definitions, grades, attribution, timing, recurrence, or exposure duration. The serious adverse-event entry lists no affected participants and no serious-event terms, while deaths are not reported. The record does not provide detail to assess how safety events were collected or classified.

The registry also does not report the trial's sample-size justification, detailed analysis plan, interim analyses, multiplicity approach, or statistical methods for confidence intervals and tests. It lists four outcome measures, while only three secondary outcomes are identified in the descriptions. The additional outcome and the statistical handling of outcomes are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

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

This completed phase II study enrolled 31 participants and evaluated gemcitabine, oxaliplatin, and panitumumab in a single group. The intended population was chemotherapy-naïve people with KRAS/BRAF wild-type, Stage IV biliary tract or gallbladder cancer described as unresectable or metastatic. The record lists a start date of 2010-12, a primary completion date of 2013-01, and University of Rochester as sponsor.

The primary outcome was the number of participants with RECIST response by the end of cycle 2. The registry describes imaging procedures but does not report the response result or its precision. The named secondary outcomes were median progression-free survival, median overall survival, and adverse events; survival results are not reported in the registry record described.

For adverse events, 31 participants were at risk and 0 were reported affected by serious adverse events; 31 were at risk and 31 were affected by other adverse events. Event-level details are not reported. The single-group design does not provide a randomized comparator, and detailed analysis methods, missing-data procedures, and analysis populations are not reported in the registry record.

Clinical Biostats