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 Pemetrexed and Bevacizumab in Patients With Head and Neck Cancer (NCT00222729), a na phase 2 study. The primary outcome is Time-to-progression (TTP).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00222729 |
| Phase | Phase 2 |
| Condition | Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pittsburgh |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns patients with recurrent or metastatic head and neck cancer. The primary outcome description refers to evaluable patients with previously untreated, recurrent, or metastatic SCCHN. The registry record does not provide further eligibility details or define the evaluable population.
Intervention
The study treatment was the combination of pemetrexed and bevacizumab. The primary outcome description specifies pemetrexed 500 mg/m2; a bevacizumab dose is not reported in the registry record. The arm description names the combination but gives no further treatment schedule.
Comparator
There was no separate comparison group: the study is listed as single-group, with allocation recorded as NA. Thus, its design does not provide a like-for-like control group against which to compare the combination.
Primary question
The primary outcome is time-to-progression, measured from treatment initiation to disease progression or last follow-up. The registry lists a median and a 90% confidence interval, with a timeframe of up to 36 months. It does not report the median or interval estimate, so the posted record does not give a numerical answer to the primary question.
3. Trial Design
This is a phase 2, completed, single-group study sponsored by the University of Pittsburgh. The registry lists enrollment of 42 and identifies pemetrexed and bevacizumab as the interventions. The study title and summary describe their use together in patients with head and neck cancer, including recurrent or metastatic disease.
Allocation is recorded as NA, and the study model is single-group. Masking is listed as none. These features describe a design without a randomized control arm and without masking. The record therefore cannot support a direct randomized comparison between the combination and another treatment or a control condition. The reason for selecting this design is not reported in the registry record.
The registry lists the study start as 2005-11 and primary completion as 2013-10. Its status is completed. The primary outcome timeframe is up to 36 months. The primary outcome population is described as evaluable patients with previously untreated, recurrent, or metastatic SCCHN treated with pemetrexed 500 mg/m2. The record does not explain how evaluability was determined, nor does it give further details about treatment schedules or follow-up procedures.
Objective response rate, disease control rate, and overall survival are named as secondary outcomes. The record lists four outcome measures, but it does not provide numerical results for those outcomes. A detailed statistical analysis plan, including the planned analysis populations and any rules for handling incomplete follow-up, is not reported in the registry record.
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 | Pemetrexed + Bevacizumab |
|---|---|
| STARTED | 40 |
| COMPLETED | 37 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Pemetrexed + Bevacizumab |
|---|---|
| Adverse Event | 3 |
Analysis population for the primary outcome, as defined in the registry: Evaluable patients with previously untreated, recurrent, or metastatic SCCHN were treated with pemetrexed 500 mg/m2
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 | Pemetrexed + Bevacizumab |
|---|---|---|
| Participants analysed | 40 | |
| Age, Continuous | years | 59 (36 to 85) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Time-to-progression (TTP), measured over Up to 36 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 90% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Time-to-progression (TTP) measures the time from treatment initiation until disease progression or last follow-up, as stated in the registry record. It is a time-to-event outcome: the endpoint concerns when an event occurs, rather than only whether an event occurred by a single fixed assessment point. The registry specifies a timeframe of up to 36 months and identifies the median as the summary measure, with a 90% confidence interval.
General statistical explanation: A median time-to-event estimate describes the point by which half of the relevant population is estimated to have experienced the event, subject to the analysis and follow-up definitions. Participants whose progression is not observed during available follow-up may contribute information up to their last known follow-up rather than being treated as if progression occurred then. This kind of incomplete event observation is commonly called censoring; the registry description’s reference to last follow-up signals that follow-up ending before documented progression matters to the endpoint definition.
TTP is used to summarize the timing of progression, but it does not by itself describe every aspect of disease course or survival. The registry record does not report a median TTP or its confidence interval, so the primary outcome’s estimated timing and precision cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies TTP as the primary outcome and states how it was defined, but it does not post a numerical median or 90% confidence interval. Consequently, the primary outcome’s observed estimate and its precision are not reported in the registry record. Without those values, it is not possible to characterize the reported time to progression numerically or assess the uncertainty around it.
The study is single-group, with allocation recorded as NA and no masking. Its design can describe outcomes among the treated group, but it does not include a randomized control group for estimating a comparative treatment effect. Even if outcome estimates were available, differences from outcomes in another population or study could reflect differences in participants, follow-up, or other features, rather than the treatment alone. The registry record does not provide a comparative result.
Objective response rate, disease control rate, and overall survival are listed as secondary outcomes. Their numerical estimates are not reported in the registry record. The record also lists four outcome measures but does not give the numerical results for those measures. No sponsor-reported hazard ratio is present in the registry record. The stated approach for time-to-event calculations elsewhere in the study’s statistical context is to use sponsor-reported hazard ratios, but that does not supply a result when no such estimate is posted.
The enrollment is 42, while the safety summaries identify 40 participants at risk in each of the serious and other adverse-event groupings. The registry record does not explain the relationship between enrollment and these safety denominators. That difference should not be interpreted as evidence about exclusion, withdrawal, or missing data without further information.
Overall, the posted record documents a completed phase 2 study and its primary endpoint definition, but it does not provide the primary numerical outcome or numerical secondary outcome results. The study design also lacks a control arm. These limitations mean the record does not establish a comparative treatment effect, and it does not allow the precision of TTP to be evaluated.
9. Statistical Methods Explained
The statistical information in the registry record is limited. It identifies a median TTP and a 90% confidence interval as the primary outcome summary, and gives the time origin and event definition. It does not report the numerical estimate, interval endpoints, or a detailed analysis plan. The explanations below distinguish the general meaning of these methods from what is documented for this study.
What does a median time-to-event estimate describe?
General statistical explanation: A time-to-event analysis uses both the timing of observed events and the follow-up information available for people who have not yet had an event. The median is a summary of the event-time distribution: it marks the estimated time by which half the analyzed population has experienced the event. It is not an average, and it does not describe the timing for every participant.
For this study, the event is disease progression, and the time origin is treatment initiation. The registry description also includes last follow-up. In general, if progression has not been observed by the end of a participant’s available follow-up, the observation is censored at that point. Censoring retains information about the time during which progression was not documented; it is not the same as documenting that progression occurred at the last follow-up.
Time-to-event methods require appropriate handling of censoring and follow-up. Their interpretation depends on the endpoint definition, the follow-up information, and the analysis population. The registry record does not report the method used to estimate the median, the censoring rules in detail, or checks of assumptions.
How should a 90% confidence interval be read?
General statistical explanation: A confidence interval communicates uncertainty around an estimate under the method used to calculate it. A narrower interval indicates greater precision than a wider interval, while the interval’s endpoints show a range of values compatible with the observed data and method. A 90% confidence interval is not a statement that there is a 90% probability that a fixed true value lies inside this particular calculated interval. The registry specifies a 90% interval but does not post its endpoints, so its width and the estimate’s precision cannot be evaluated.
What would a hazard ratio contribute?
General statistical explanation: A hazard ratio compares event rates over time between groups under a time-to-event model. It is a relative comparison, not a median time and not a direct description of how many participants experienced an event. Interpretation depends on the groups being compared and on the model’s assumptions. A single-group study does not itself supply a randomized between-group contrast. No sponsor-reported hazard ratio is reported in the registry record, so there is no such estimate to interpret for this study.
What do the planning assumptions mean?
General statistical explanation: A planning illustration asks how much information a hypothetical design might need to detect a specified effect under stated assumptions. The assumptions listed for the illustration include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustration expresses the requirement as a total number of events using the Schoenfeld method; for other outcomes, it expresses the requirement as participants per arm.
These are planning calculations, not evidence that the trial had a particular probability of detecting an effect. They are not observed power, and they are not the trial’s own design justification. In particular, the hypothetical equal-allocation comparison does not change the fact that this study is recorded as single-group. The registry record does not report the trial’s sample-size justification or the numerical results of planning calculations.
Interpretation of any statistical estimate also depends on the analysis population, outcome ascertainment, and missing-data handling. Those details are not fully reported in the registry record. The primary outcome description identifies evaluable patients, but does not define that term. No analysis estimates are posted, and the record does not specify whether or how any interim analyses were planned.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists TTP as the primary outcome and names objective response rate, disease control rate, and overall survival as secondary outcomes. It also records four outcome measures. However, numerical results for these measures are not reported in the registry record. The record does not describe a hierarchy for testing outcomes, an adjustment for multiple comparisons, or a prespecified rule for interpreting several statistical tests. The multiplicity strategy is therefore not reported in the registry record.
Multiplicity matters in general because evaluating several outcomes or conducting several statistical tests can increase the chance that at least one result appears notable by chance. A prespecified testing plan or an adjustment method can address that issue, but the appropriate approach depends on the study’s objectives and analysis plan. No such plan is described in the registry record, so it would be inappropriate to assume that an adjustment was or was not used.
The registry record does not report a missing-data method, censoring details beyond the TTP definition’s reference to last follow-up, or the number of participants included in each efficacy analysis. The primary outcome description refers to evaluable patients, but the criteria for being evaluable and the size of that analysis population are not reported in the registry record. The record also does not describe sensitivity analyses for incomplete outcome data.
No statistical analysis results are listed. Interim analyses and stopping rules are not reported in the registry record. Without these details, readers cannot determine how many analyses were conducted, how incomplete information was addressed, or how the analysis populations were defined beyond the brief primary outcome description.
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 |
|---|---|---|---|
| Pemetrexed + Bevacizumab | 28 | 40 | 70.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pemetrexed + Bevacizumab | 40 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Pemetrexed + Bevacizumab |
|---|---|---|
| Bleeding | Blood and lymphatic system disorders | 6 of 40 |
| Infection-other | Infections and infestations | 5 of 40 |
| Neutropenia | Blood and lymphatic system disorders | 4 of 40 |
| Anemia | Blood and lymphatic system disorders | 2 of 40 |
| Fatigue | General disorders | 2 of 40 |
| Hypokalemia | Metabolism and nutrition disorders | 2 of 40 |
| Hyponatremia | Metabolism and nutrition disorders | 2 of 40 |
| Anorexia | Metabolism and nutrition disorders | 1 of 40 |
| AST increase | Metabolism and nutrition disorders | 1 of 40 |
| Edema | Blood and lymphatic system disorders | 1 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pemetrexed + Bevacizumab |
|---|---|---|
| Fatigue (asthenia, lethargy, malaise) | General disorders | 20 of 40 |
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | 13 of 40 |
| Hemoglobin | Blood and lymphatic system disorders | 13 of 40 |
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | 10 of 40 |
| Lymphopenia | Blood and lymphatic system disorders | 10 of 40 |
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | 10 of 40 |
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | 9 of 40 |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | 7 of 40 |
| Nausea | Gastrointestinal disorders | 7 of 40 |
| Weight loss | General disorders | 7 of 40 |
Serious events with the highest arm-level rate: bleeding (15.0%), infection-other (12.5%), neutropenia (10.0%), anemia (5.0%), fatigue (5.0%).
The registry lists 40 participants at risk for serious adverse events, with 28 affected. For other adverse events, it lists 40 participants at risk and 40 affected. These are separate safety summaries; the record does not explain the relationship between the safety denominators and the enrolled total of 42.
The serious adverse-event terms with the largest listed percentages are bleeding, 15.0%; infection-other, 12.5%; neutropenia, 10.0%; anemia, 5.0%; fatigue, 5.0%; and hypokalemia, 5.0%. These percentages are reported as registry entries. The record does not provide further details about event timing, recurrence, severity grading, or how the percentages were calculated. It also does not report a value for deaths.
General statistical explanation: A participant count and a list of event terms describe different aspects of safety. A participant may experience more than one event, so event counts and counts of affected participants are not interchangeable. Without fuller definitions and follow-up details, these summaries should not be read as a complete account of the frequency or timing of every adverse event.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase 2 study of pemetrexed and bevacizumab in a single group of patients with head and neck cancer. It defines TTP as time from treatment initiation to disease progression or last follow-up, and identifies a median and 90% confidence interval as the primary summary. Those numerical results are not reported in the registry record.
This means the posted information does not permit an assessment of the observed median TTP or the precision of that estimate. Numerical results for the listed secondary outcomes are also not reported. Safety summaries include counts of participants affected and percentages for selected serious adverse-event terms, but the record does not provide enough detail to interpret event timing, repeated events, or the basis for every percentage.
The absence of a separate control group is central to interpretation. A single-group study can describe outcomes observed among participants receiving the study combination, but it cannot provide a randomized comparison with another treatment or with no treatment. It therefore cannot isolate the effect of the combination from other explanations for the observed outcomes. In this case, the registry record also lacks the numerical efficacy estimates needed to describe those outcomes.
General statistical explanation: A study’s design, outcome estimates, and uncertainty all contribute to what can be concluded. A defined endpoint is not itself a result, and a completed study status does not supply missing numerical outcomes. The record supports a description of the study question and design, but not a numerical conclusion about TTP or a comparative treatment effect.
13. Why This Trial Matters Statistically
This study illustrates why outcome definitions and outcome results need to be read separately. The registry gives a clear starting point and event definition for TTP: treatment initiation to disease progression or last follow-up. It also identifies the planned summary as a median with a 90% confidence interval. Yet the numerical estimate and interval are not reported in the registry record. Knowing the endpoint definition does not reveal the observed outcome.
Its single-group design also matters statistically. Without a control arm, the study can describe the treated group but cannot make a randomized comparison. This distinction remains important even when a trial has a named primary outcome and a completed status. Comparative claims require a basis for comparing groups that the recorded design does not include.
The record also shows why safety summaries require attention to denominators and definitions. It lists 40 participants at risk for serious adverse events and 40 at risk for other adverse events, while enrollment is recorded as 42. The reason for the difference is not reported in the registry record. Selected serious-event terms and percentages are listed, but details about event counting and timing are not.
General statistical lesson: Statistical interpretation relies on more than a study title or endpoint label. The design, analysis population, outcome estimates, uncertainty, and handling of incomplete observations all contribute. When key results or methods are absent, that absence limits what can be inferred; it should not be replaced by assumptions about what the analysis might have shown.
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 main limitation for interpreting efficacy is that the registry record does not report the numerical TTP result, despite identifying it as the primary outcome and specifying a median with a 90% confidence interval. Numerical results for the named secondary outcomes are also not reported. As a result, neither the magnitude nor precision of the efficacy outcomes can be evaluated from the posted record.
The study is single-group and has no randomized comparator. This prevents a direct randomized estimate of the combination’s effect relative to another treatment. Allocation is listed as NA and masking as none. The record does not explain the rationale for the design or provide details that would support a comparative analysis.
The primary outcome population is described as evaluable patients with previously untreated, recurrent, or metastatic SCCHN, but the record does not define evaluability or report the size of that population. It does not describe missing-data procedures, censoring rules in detail, or sensitivity analyses. The safety summaries list 40 participants at risk, while the enrollment is 42; the relationship between these figures is not explained. A value for deaths is not reported.
Further limitations include the absence of a detailed statistical analysis plan, a stated multiplicity approach, interim-analysis information, and a sample-size justification. The registry record does not report treatment schedules beyond the stated pemetrexed dose in the primary outcome description, or a bevacizumab dose. These omissions constrain interpretation but do not establish what the unreported methods or results were.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Pemetrexed and Bevacizumab in Patients With Head and Neck Cancer — NCT00222729.
- Registry record last updated 2016-02-15; status last verified 2016-01.
- Results first posted 2016-02-15.
- 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
NCT00222729 is a completed phase 2, single-group study sponsored by the University of Pittsburgh. It evaluates pemetrexed and bevacizumab in patients with recurrent or metastatic head and neck cancer. The registry lists enrollment of 42, allocation as NA, and masking as none.
The primary outcome is TTP, defined from treatment initiation to disease progression or last follow-up, with a median and 90% confidence interval specified over a timeframe of up to 36 months. The numerical TTP estimate and interval are not reported in the registry record. Objective response rate, disease control rate, and overall survival are listed as secondary outcomes, but their numerical results are not reported.
Safety entries list 28 participants affected among 40 at risk for serious adverse events, and 40 affected among 40 at risk for other adverse events. The registry also lists selected serious adverse-event terms and percentages. The record does not provide a control-group comparison or a detailed statistical analysis plan.