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 Paclitaxel vs Paclitaxel + Cetuximab in Recurrent - Metastatic Head & Neck Carcinoma After Failure of a 1º Chemotherapy (NCT03887442), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03887442 |
| Phase | Phase 2 |
| Condition | Head and Neck Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Grupo Español de Tratamiento de Tumores de Cabeza y Cuello |
| Results posted | Yes |
2. Clinical Question
Population
People with recurrent and/or metastatic squamous head and neck carcinoma after failure of a first-line EXTREME-type treatment. The brief summary specifies patients undergoing maintenance treatment with cetuximab. The record notes that 17 participants were recruited and that two did not meet some inclusion and/or exclusion criteria.
Intervention
Cetuximab plus paclitaxel. The arm description specifies cetuximab 250 mg/m2 and paclitaxel 80 mg/m2, both infused intravenously every week, with cetuximab administered before paclitaxel.
Comparator
Paclitaxel alone, described as 80 mg/m2 infused intravenously every week. The record identifies a randomized, parallel-group design and no masking.
Primary question
Which treatment arm would have the more favorable progression-free survival, defined as time from study inclusion until documented disease progression or death from any cause? The registry record says the primary endpoint was not analyzed because the study closed early after insufficient accrual.
3. Trial Design
This was a phase II randomized clinical trial with a parallel-group structure and no masking. It compared paclitaxel with cetuximab plus paclitaxel in people with recurrent and/or metastatic squamous head and neck carcinoma after failure of a first-line EXTREME-type treatment. The brief summary describes the setting as progression after first-line treatment in patients undergoing maintenance treatment with cetuximab. The registry record does not report the randomization sequence method or allocation concealment.
The paclitaxel arm was described as weekly intravenous paclitaxel 80 mg/m2. The combination arm was described as weekly intravenous cetuximab 250 mg/m2 and paclitaxel 80 mg/m2, with cetuximab administered first. The record does not report treatment duration, dose-modification rules, or a detailed schedule for stopping treatment.
Enrollment was 17, compared with a planned protocol number of 80. The record says the study was prematurely closed at 19 months due to lack of accrual and gives terminated as the study status. Two recruited participants did not meet some inclusion and/or exclusion criteria; the record does not say how those participants were handled in each analysis population. The database lock date was 3 June 2013.
The primary endpoint was progression-free survival, with secondary outcomes listed as overall survival, percentage of objective response, participants with adverse events, and treatment compliance. No outcome analyses are listed in the registry record. The primary endpoint was explicitly not analyzed. The record does not report a detailed statistical analysis plan, sample-size justification, interim analyses, or the methods used to assess the secondary outcomes.
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 | Paclitaxel | Cetuximab + Paclitaxel |
|---|---|---|
| STARTED | 9 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Paclitaxel | Cetuximab + Paclitaxel |
|---|---|---|
| Adverse Event | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Only 17 patients out of a planned protocol number of 80 were recruited to the study, owing to premature closure of the study. Two of those patients did not meet some of the inclusion and/or exclusion criteria. Database lock: 3 June 2013. There were insufficient numbers of patients to be able to analyse the efficacy endpoints. The possible discrepancies that were pending resolution have been closed as "Premature closure of the study. Deviation DN13/024". .
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 | Paclitaxel | Cetuximab + Paclitaxel | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 8 | 17 | |
| Age, Continuous | years | 63.16 (SD 7.25) | 58.48 (SD 8.76) | 60.96 (SD 8.11) |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 8 | 6 | 14 |
| Region of Enrollment: Spain | Participants | 9 | 8 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), measured over Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The primary endopoint was not analyzed..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Progression-free survival (PFS) was the primary endpoint. The registry definition starts the measurement at inclusion in the study and ends it when disease progression or death from any cause is documented. This endpoint combines disease progression and death into a time-to-event measure: it captures how long participants remain alive without documented progression, rather than measuring only whether progression occurred at a particular visit.
General: Time-to-event endpoints are useful when participants can have events at different times and when follow-up may end before every participant experiences an event. A statistical analysis can use the timing of events and account for participants whose event status is not known at the end of their follow-up. Such an approach requires a prespecified definition of events and follow-up, and appropriate handling of incomplete observation.
The registry record describes the intended primary comparison as selecting the more effective arm based on PFS reached in each treatment arm. However, it also states that the study closed early due to lack of accrual and that the primary endpoint was not analyzed. No arm-specific PFS results, effect estimate, confidence interval, or statistical test result is reported in the registry record. Therefore, the endpoint definition is available, but a comparison of the treatments on PFS is not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the intended question and the reason the primary result is unavailable. This was a randomized phase II study of paclitaxel alone versus cetuximab plus paclitaxel. It enrolled 17 participants against a planned protocol number of 80, then closed prematurely at 19 months because of lack of accrual. The registry record states that PFS, the primary endpoint, was not analyzed. Consequently, there is no reported estimate of the difference between arms in PFS, no confidence interval describing its precision, and no primary-endpoint test result to interpret.
Randomization is intended to make treatment groups comparable on average at the start of a trial, but it does not guarantee balance in every small study. With 17 participants recruited, chance imbalances may be consequential. The record does not provide baseline characteristics or an analysis population, so the degree of balance and the handling of the two participants who did not meet some criteria cannot be assessed. This limits interpretation beyond the simple description of the trial design.
The adverse-event record lists participants at risk and affected in each arm, as well as deaths. These are descriptive counts, not a comparative estimate of treatment-related risk. In the paclitaxel arm, 9 were at risk for serious adverse events and 4 were affected; in the combination arm, 8 were at risk and 4 were affected. The record lists 6 deaths in the paclitaxel arm and 4 in the combination arm, but does not report whether deaths were attributed to treatment, disease, or another cause. Counts in small groups do not by themselves establish a treatment effect.
Several serious adverse-event terms are listed with 12.5% each. The record does not report the denominator used for those percentages or whether the terms represent unique participants, event episodes, or another reporting unit. The safety information therefore has to be read as a limited set of registry counts and terms, rather than as a complete comparative safety analysis.
The absence of an analyzed PFS endpoint is not evidence that the two treatments had the same outcome, nor does it establish that either treatment was better. The registry record does not report effect estimates for the listed secondary outcomes or analyses of them. Any claim about comparative efficacy or a statistically established difference would go beyond the results recorded.
9. Statistical Methods Explained
General: A randomized parallel-group trial assigns participants to separate treatment groups and compares outcomes between those groups. Random assignment is intended to reduce systematic differences at enrollment, including differences that may not be measured. It does not ensure that every characteristic will be balanced, particularly when group sizes are small. The registry record identifies randomization and a parallel model but does not report the sequence-generation method, allocation concealment, or baseline characteristics.
General: Masking refers to keeping participants, clinicians, assessors, or analysts unaware of assigned treatment. The record identifies the trial as having no masking. It does not specify which people involved in the study knew treatment assignments, or whether outcome assessment procedures included safeguards against knowledge of assignment. For outcomes requiring clinical judgment, lack of masking can potentially influence assessment or decisions. That is a general consideration, not a claim that such influence occurred in this trial.
General: PFS is a time-to-event outcome. Each participant contributes information from the defined start point until progression or death is documented, or until follow-up ends without a documented event. When follow-up ends before an event, the observation is commonly treated as censored: the participant contributes time observed, but the event time is not known. Valid interpretation depends on how progression is defined, how events are confirmed, how follow-up is conducted, and how censoring is handled. The registry record defines the endpoint as time from inclusion until documented progression or death from any cause, but does not report the event-assessment schedule, censoring rules, or the statistical method planned for PFS.
General: Common tools for time-to-event analysis include survival curves, tests comparing event-time distributions, and regression models that estimate a relative event rate while accounting for follow-up time. These methods answer related but not identical questions. A survival curve describes the probability of remaining event-free over time; a test assesses evidence of a difference between groups under its assumptions; and a regression model can adjust for specified characteristics. No such method or result is reported for this trial’s primary endpoint, which the record says was not analyzed. It would therefore be incorrect to attribute any particular time-to-event method to the investigators.
General: A confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. Wider intervals indicate less precision, while an interval that includes values compatible with no difference does not prove equivalence. A p-value, when used, describes how compatible observed data are with a specified null model; it is not the probability that a treatment works or that the null hypothesis is true. The registry record reports no PFS estimate, confidence interval, or p-value, so none can be interpreted for the primary question.
The record lists secondary outcomes of overall survival, percentage of objective response, participants with adverse events, and treatment compliance. These outcomes require different definitions and analyses. Overall survival is also a time-to-event outcome, whereas objective response generally depends on defined response criteria and assessment timing. Adverse-event summaries may count participants, events, severity categories, or relationships to treatment; treatment compliance requires its own definition. The registry record does not provide methods for these measures or analyses of them.
General: Over-dispersion occurs when the variability in count data exceeds what a statistical model assumes. It can make standard errors too small if ignored, producing intervals that are too narrow and tests that appear more decisive than warranted. Count outcomes can also have many zeros or uneven event rates, so model choice should match the outcome and data structure. The record does not describe an over-dispersion analysis or a count-data model; this is a general statistical consideration, not a reported feature of the trial.
The record gives a planning illustration framework based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that time-to-event illustrations use total events and other illustrations use participants per arm. These assumptions describe planning calculations, not results observed in the trial and not necessarily the trial’s original design. No calculated illustration values or observed primary effect are reported in the record. The study’s planned protocol number of 80 is recorded, but a sample-size justification is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome, PFS, and several secondary outcomes: overall survival, percentage of objective response, participants with adverse events, and treatment compliance. The primary endpoint was not analyzed. No outcome analyses are listed in the registry record, and results for the secondary efficacy outcomes are not reported in the registry record.
Multiplicity arises when several outcomes, time points, or statistical comparisons are tested. Without a plan for controlling or interpreting the accumulation of tests, the chance of finding at least one apparently notable result can increase. This is a general concern when multiple outcomes are assessed, not evidence that the trial conducted multiple tests. The record does not report a multiplicity adjustment or a prespecified hierarchy for secondary outcomes.
Missing data can affect both the amount of information available and the validity of an estimate, depending on why observations are absent and how the analysis handles them. The registry record does not report missing-data amounts, reasons, imputation methods, or sensitivity analyses. It also does not report the analysis populations, such as whether analyses were intended to include all randomized participants or a subset defined by treatment received or eligibility.
The record states that 17 participants were recruited and that two did not meet some inclusion and/or exclusion criteria. It does not say whether those participants were randomized, whether they received study treatment, or how they were included in any safety or outcome summaries. These details are not reported in the registry record. The early closure and lack of an analyzed primary endpoint prevent assessment of how planned analysis choices would have affected the result.
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 |
|---|---|---|---|
| Paclitaxel | 4 | 9 | 44.4% |
| Cetuximab + Paclitaxel | 4 | 8 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Paclitaxel | 6 of 9 |
| Cetuximab + Paclitaxel | 4 of 8 |
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 |
|---|---|
| Paclitaxel | 9 of 9 |
| Cetuximab + Paclitaxel | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Paclitaxel | Cetuximab + Paclitaxel |
|---|---|---|---|
| Vomiting | Gastrointestinal disorders | 0 of 9 | 1 of 8 |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 1 of 8 |
| Fracture of humerus | Injury, poisoning and procedural complications | 1 of 9 | 0 of 8 |
| Lung infection | Infections and infestations | 0 of 9 | 1 of 8 |
| Pneumococcal pneumonia | Infections and infestations | 1 of 9 | 0 of 8 |
| Abdominal pain | Gastrointestinal disorders | 0 of 9 | 1 of 8 |
| Mouth bleeding | Gastrointestinal disorders | 1 of 9 | 0 of 8 |
| Pneumonia | Infections and infestations | 0 of 9 | 1 of 8 |
| Infection | Infections and infestations | 0 of 9 | 1 of 8 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 9 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Paclitaxel | Cetuximab + Paclitaxel |
|---|---|---|---|
| Asthenia | General disorders | 5 of 9 | 5 of 8 |
| Mucosal inflammation | General disorders | 3 of 9 | 6 of 8 |
| Alopecia | Skin and subcutaneous tissue disorders | 4 of 9 | 2 of 8 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 9 | 3 of 8 |
| Dysphagia | Gastrointestinal disorders | 2 of 9 | 2 of 8 |
| Diarrhea | Gastrointestinal disorders | 2 of 9 | 2 of 8 |
| Loss of appetite | Metabolism and nutrition disorders | 2 of 9 | 2 of 8 |
| Constipation | Gastrointestinal disorders | 1 of 9 | 3 of 8 |
| Peripheral neuropathy | Nervous system disorders | 2 of 9 | 1 of 8 |
| Nausea | Gastrointestinal disorders | 2 of 9 | 1 of 8 |
Serious events with the highest arm-level rate: vomiting (12.5%), bronchospasm (12.5%), lung infection (12.5%), abdominal pain (12.5%), pneumonia (12.5%).
The registry lists serious adverse-event counts separately by treatment arm. For paclitaxel, 9 participants were at risk and 4 were affected. For cetuximab plus paclitaxel, 8 participants were at risk and 4 were affected. The record also lists other adverse events: 9 participants at risk and 9 affected in the paclitaxel arm, and 8 at risk and 8 affected in the combination arm. These are counts as recorded, not evidence by themselves of a causal difference between treatments.
The record lists 6 deaths in the paclitaxel arm and 4 in the combination arm. It does not report whether these deaths were considered treatment-related, nor does it provide causes of death or a comparative analysis. Death counts should not be interpreted as treatment effects without that context and an appropriate analysis.
Vomiting, bronchospasm, lung infection, abdominal pain, pneumonia, and infection are each listed among the top serious adverse-event terms, with 12.5% attached to each. The denominator and reporting unit for these percentages are not reported in the registry record. The listed terms may not capture the full safety profile, and their presentation does not establish a comparative frequency or treatment relationship.
12. What the Result Does, and Does Not, Mean
The registry record answers a limited set of descriptive questions: it identifies the treatments compared, the intended PFS endpoint, the enrollment shortfall, the reason for early closure, and selected adverse-event counts. It does not provide an analyzed primary efficacy result. Since the PFS endpoint was not analyzed, there is no reported estimate showing how the arms compared on the primary outcome and no measure of the precision of such a comparison.
That absence should not be mistaken for a finding of no difference. A trial that does not produce an analyzed endpoint cannot establish that treatments are equivalent, nor can it establish that one is superior. The study’s randomized design describes how treatment assignment was intended to occur, but randomization alone does not create an outcome estimate when the endpoint was not analyzed.
The adverse-event counts are also limited. They describe participants affected in each arm and deaths recorded, but the registry does not give attribution, detailed event timing, or a comparative safety analysis. The serious-event percentages have no reported denominator. Those entries can be described, but they do not support a firm conclusion about relative safety.
The study enrolled 17 participants despite a planned protocol number of 80 and was terminated early because of lack of accrual. The record does not report a sample-size justification or the actual analysis plan. The planned number should not be treated as an estimate of what the trial achieved, and any planning illustration based on an observed effect should not be mistaken for observed power or a trial result. No observed PFS effect is reported in the registry record.
Accordingly, the most defensible interpretation is that the trial record documents an intended randomized comparison but does not report the primary efficacy comparison. The listed safety counts remain descriptive, and no comparative conclusion about efficacy or treatment-related harm is established by these data.
13. Why This Trial Matters Statistically
This trial matters statistically because its design and its recorded outcome availability are distinct. It was randomized and intended to compare two treatment strategies using PFS, but early termination after low accrual left the primary endpoint unanalyzed. A randomized design can support a meaningful comparison when outcome data and an appropriate analysis are available; it cannot substitute for those results.
The enrollment information also illustrates why sample size and precision matter. The protocol planned for 80 participants, while 17 were recruited. A smaller-than-planned study generally has less information available to estimate an effect precisely. That is a general statistical principle, not a calculated power statement about this trial. The registry record reports no effect estimate or confidence interval from which to assess the magnitude or precision of a PFS comparison.
The safety information raises a related interpretive issue. Counts from small treatment groups can look different or similar by chance, and the listed serious adverse-event percentages lack a reported denominator. Without a specified analysis and fuller context, simple counts do not establish relative risk or attribution.
Finally, the registry record shows why outcome definitions and transparent reporting matter. The PFS definition is stated, but no analyzed result is reported; listed secondary outcomes do not have reported methods or results. This leaves readers able to identify the intended clinical question and the trial’s operational outcome, while preventing a reliable statistical conclusion about comparative efficacy. The distinction between a study that was designed to answer a question and one that reported an answer is central to interpreting clinical trial evidence.
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 central limitation is that the primary PFS endpoint was not analyzed. Although the record defines PFS and identifies it as the primary endpoint, it gives no arm-specific outcome, effect estimate, confidence interval, or test result. The study’s premature closure at 19 months due to lack of accrual is the stated reason the planned comparison could not be reported.
Enrollment was 17, compared with a planned protocol number of 80. The record does not report why accrual was insufficient beyond stating lack of accrual, and it does not provide a sample-size justification. Two participants did not meet some inclusion and/or exclusion criteria, but their allocation, treatment exposure, and handling in analyses are not reported in the registry record.
The record identifies the study as randomized and unmasked, but does not report the randomization method, allocation concealment, baseline characteristics, or which personnel knew treatment assignments. It does not report the statistical analysis plan, censoring rules, endpoint assessment details, or analysis populations. The record also does not report missing-data procedures or sensitivity analyses.
Secondary outcomes are named but their results and analysis methods are not reported in the registry record. Safety entries include counts and serious adverse-event terms, but treatment attribution, causes of death, and the denominator for the listed 12.5% terms are not reported. These limitations mean that the available record supports description of the study design and selected safety entries, but not a complete assessment of efficacy or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Paclitaxel vs Paclitaxel + Cetuximab in Recurrent - Metastatic Head & Neck Carcinoma After Failure of a 1º Chemotherapy — NCT03887442.
- Registry record last updated 2021-01-07; status last verified 2020-12.
- Results first posted 2020-12-09.
- 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
The registry record describes a phase II randomized, parallel-group trial with no masking. It compared weekly intravenous paclitaxel 80 mg/m2 with weekly intravenous cetuximab 250 mg/m2 plus paclitaxel 80 mg/m2 in recurrent and/or metastatic squamous head and neck carcinoma after failure of a first-line EXTREME-type treatment.
The primary endpoint was PFS, defined as time from inclusion until documented disease progression or death from any cause. The record states that the study closed prematurely at 19 months due to lack of accrual and that the primary endpoint was not analyzed. Enrollment was 17 against a planned protocol number of 80; two participants did not meet some inclusion and/or exclusion criteria. Secondary outcomes were listed, but their analyses are not reported. The record includes selected adverse-event counts and deaths, without a comparative safety analysis or reported attribution.