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 Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma (NCT00754494), a randomized phase 2 study. The primary outcome is Change in ACF pERK Levels.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00754494 |
| Phase | Phase 2 |
| Condition | Adenomatous Polyp, Recurrent Colon Cancer, Recurrent Rectal Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with stage I-III colorectal cancer or adenoma were eligible for the study. The registry record also lists adenomatous polyp and recurrent colon or rectal cancer among the conditions. Further eligibility details, such as how these groups were selected or their baseline characteristics, are not reported in the registry record.
Intervention
The study examined daily oral erlotinib hydrochloride at 25 mg, 50 mg, or 100 mg. The registry describes placebo tablets alongside the active dose in each arm. Laboratory biomarker analysis was also listed as an intervention.
Comparator
The listed arms compare three erlotinib dose levels. The registry record does not describe a placebo-only arm. Because the trial was randomized and triple masked, assignment and masking were features of its design; the specific parties included in triple masking are not reported in the registry record.
Primary question
The primary question concerned change in pERK levels in aberrant crypt foci (ACF) from baseline to post-treatment, up to 30 days. The registry record says the assay did not demonstrate signaling, so the primary outcome is not reported as a measured change. The record therefore does not establish a quantitative comparison among the dose groups for this endpoint.
The official title frames the study around inhibition of EGF receptor signaling in ACF of the colon. Its primary endpoint focused on pERK levels in ACF, while the registry also lists outcomes involving EGFR markers, the ACF-to-normal-mucosa pERK ratio, and plasma or tissue concentrations. These are biomarker and concentration outcomes; the listed primary endpoint is not a clinical outcome such as recurrence, survival, or symptoms.
The trial was conducted in patients described as having stage I-III colorectal cancer or adenoma. The record does not report results that would show whether any dose changed the primary biomarker, nor does it report a primary endpoint comparison by dose. The central question can therefore be described, but its answer cannot be estimated from the posted primary outcome information.
3. Trial Design
This was a randomized, triple-masked, parallel-group phase IIa trial sponsored by the National Cancer Institute (NCI). The registry lists an enrollment of 45 and three erlotinib dose groups: 25 mg, 50 mg, and 100 mg, each taken orally once daily. The arm descriptions also include placebo tablets alongside the active dose. No placebo-only arm is described in the registry record.
In a parallel-group design, participants are assigned to a group and the groups are compared during the study rather than having each participant receive every assigned regimen in sequence. Randomization is intended, in general, to reduce systematic differences in assigned groups at the outset. It does not guarantee that groups will be identical, especially in a trial with a limited enrollment. The registry record does not report the randomization method or the baseline characteristics needed to assess group balance.
The trial is marked triple masked. Masking can reduce the influence of knowledge about assignment on participant experience, treatment delivery, or outcome assessment, depending on who is masked. Which parties were masked, and how masking was implemented, are not reported in the registry record. The presence of placebo tablets in the arm descriptions is recorded, but the record does not provide enough detail to infer masking procedures beyond the stated designation.
The study started in 2008-07, reached primary completion in 2012-10, and is marked completed. Its primary endpoint timeframe was from baseline to post-treatment, up to 30 days. The registry record does not report the duration of treatment or the detailed visit schedule beyond that endpoint timeframe. It lists 13 outcome measures and 12 analyses, but does not describe the full analysis plan or explain how those outcomes and analyses correspond.
The trial design was directed toward a biomarker question rather than a direct comparison of clinical events. The registry record does not report a sample-size justification, the planned detectable effect, or an allocation ratio beyond the group descriptions. It also does not report whether any interim analyses were planned or conducted.
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 | Arm I (25 mg) | Arm II (50 mg) | Arm III (100 mg) |
|---|---|---|---|
| STARTED | 15 | 15 | 15 |
| COMPLETED | 13 | 15 | 14 |
| NOT COMPLETED | 2 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Change in ACF pERK levels not reported as the assay did not demonstrate signaling
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 (25 mg) | Arm II (50 mg) | Arm III (100 mg) | Total |
|---|---|---|---|---|---|
| Participants analysed | 15 | 15 | 15 | 45 | |
| Age, Continuous | years | 63.67 (SD 4.43) | 62.47 (SD 6.03) | 60.67 (SD 7.42) | 62.27 (SD 6.08) |
| Sex: Female, Male: Female | Participants | 2 | 1 | 5 | 8 |
| Sex: Female, Male: Male | Participants | 13 | 14 | 10 | 37 |
6. Primary Endpoint
The registry lists the primary outcome as Change in ACF pERK Levels, measured over From baseline to post-treatment (up to 30 days).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in pERK levels in aberrant crypt foci (ACF), assessed from baseline to post-treatment, up to 30 days. The registry states that quantification would use Western blot analysis and that the planned test was a paired t-test with a two-sided significance level of 0.05. A paired analysis is generally used when measurements are made on the same participant at different times, because it evaluates within-participant change rather than treating the measurements as unrelated.
The endpoint was selected to examine a biomarker associated in the trial title with EGF receptor signaling in ACF. In general, a biomarker endpoint can help assess whether a biological signal changes during a study, but a change in a biomarker is not by itself a clinical outcome. It does not directly measure disease recurrence, survival, or how participants feel or function.
The registry record states that change in ACF pERK levels was not reported because the assay did not demonstrate signaling. This is not a numerical estimate of change and does not provide a confidence interval or test result for the planned endpoint. The record therefore does not allow a reader to quantify the biomarker response or compare it across the three dose groups.
The other listed outcomes include EGFR markers in normal mucosa and ACF, the ACF-to-normal-mucosa pERK ratio, and erlotinib or OSI-420 concentrations in plasma or normal mucosa. Their presence provides context for the biomarker focus, but it does not substitute for a reported primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint result cannot be interpreted as a measured treatment effect from the registry record. Although the record names change in ACF pERK levels as the primary outcome and specifies a paired t-test, it states that the assay did not demonstrate signaling and that the change was not reported. No group-specific change estimate, uncertainty interval, or primary endpoint p-value is reported. Consequently, the posted information does not quantify whether pERK changed from baseline or whether changes differed among the dose groups.
An assay that does not demonstrate signaling is a measurement limitation for this endpoint. It does not establish that pERK was unchanged, that signaling was absent in participants, or that erlotinib had no biological effect. Those conclusions would require interpretable assay results and an analysis appropriate to the study question. The registry record does not provide those results or details about the assay's performance beyond the statement that signaling was not demonstrated.
The trial's design can still be described: participants were randomized among three dose groups, and the study was triple masked and parallel. Those design features do not replace an outcome estimate. Randomization helps support causal interpretation when outcomes are measured and analyzed as planned, but the primary endpoint information does not provide a usable estimate of the effect or its precision.
The record lists 13 outcome measures and 12 analyses, including biomarker and drug-concentration outcomes. It does not report enough detail to determine which analyses correspond to which outcomes, whether all outcomes were measured successfully, or which results were prespecified. The absence of a primary result should therefore not be filled in by treating secondary outcomes as substitutes. Results for the other listed outcomes are not described in the registry record for this analysis.
Safety information is recorded separately. The serious adverse event counts are 1 in the 25 mg arm and 0 in each of the 50 mg and 100 mg arms, with 15 at risk in each listed group. The record also reports other adverse events in each group and lists chest pain as a top serious term at 6.7%. These figures describe recorded events; without further detail about event definitions, timing, severity, attribution, or follow-up, they do not establish comparative safety.
Planning illustrations based on an observed effect are not trial results and are not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The record does not report the observed effect needed to interpret such illustrations as a particular design target. In any case, a planning calculation cannot repair the missing primary endpoint estimate.
Overall, the registry record documents a randomized biomarker-focused study but does not provide a quantitative primary endpoint result. The appropriate reading is that the primary assay outcome was not reported because signaling was not demonstrated, not that a specific direction or size of treatment effect was observed.
9. Statistical Methods Explained
The statistical methods named for the primary endpoint are Western blot quantification and a paired t-test. The registry specifies a two-sided significance level of 0.05. It does not report the detailed statistical methods used for the other outcomes, the analysis populations, or the handling of incomplete measurements.
What does a paired t-test assess?
In general, a paired t-test evaluates the average within-participant difference between two related measurements. For this endpoint, the planned comparison was between baseline and post-treatment pERK levels. Pairing is useful when both measurements come from the same participant because it accounts for the fact that repeated measurements on one person are related. The test relies on the differences being suitable for the method; the registry record does not report diagnostic checks or any alternative analysis.
A paired test of change within a group is not automatically a direct comparison of the randomized groups. If the scientific question is whether changes differ by dose, an analysis must compare the dose groups' changes or otherwise model the treatment groups and time measurements together. The registry record names a paired t-test but does not report a group-comparison method for the primary endpoint. The distinction matters: a within-group change and a between-group treatment contrast answer different questions.
What does a two-sided significance level mean?
In general, a two-sided test allows evidence for a difference in either direction, rather than considering only an increase or only a decrease. A significance level sets a threshold for how unusual the data would need to be under a specified statistical model to be called statistically significant. The registry's stated level is 0.05. This threshold does not describe the size or clinical importance of an effect, and it is not the probability that a conclusion is correct.
A p-value, if reported, would need to be interpreted alongside an effect estimate, its uncertainty, the analysis plan, and the endpoint's measurement quality. The registry record does not report a primary endpoint p-value or estimate. Because the assay did not demonstrate signaling, there is no reported primary measurement to which the stated test can be applied in the posted results.
Why does precision matter?
In general, a confidence interval expresses a range of effect values compatible with the data and the statistical model at a stated confidence level. A narrow interval indicates greater precision than a wide interval, while an interval spanning meaningfully different possibilities can leave the magnitude uncertain. No primary endpoint confidence interval is reported in the registry record. Without an estimate and its uncertainty, readers cannot judge the precision of a dose-related effect.
Sample-size calculations are planning tools. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a fraction of the observed effect. For time-to-event outcomes, the stated illustrations use a total number of events; other illustrations use participants per arm. These are planning conventions, not observed trial findings or evidence of observed power. The registry record does not report the numerical illustration values or the trial's own sample-size justification in the registry record.
What can the registry's outcome counts tell us?
The record lists 13 outcome measures and 12 analyses. These counts indicate that multiple outcomes and analyses were registered, but they do not reveal the relationship between each measure and analysis. The record does not specify which outcomes were primary or secondary beyond the named primary endpoint, how all tests were conducted, or whether adjustments for multiple comparisons were planned. Counts alone do not establish that every outcome was analyzed or reported.
When many outcomes or comparisons are examined, the chance of at least one seemingly notable result can increase. As a general statistical principle, multiplicity methods can control that risk, but the appropriate method depends on the analysis plan and the scientific purpose. The record does not report a multiplicity adjustment. It is therefore not possible to infer whether the analyses were adjusted, whether a hierarchy was used, or how results across outcomes should be interpreted together.
Other general considerations include missing data, assay reliability, and model assumptions. The registry record does not report the amount or pattern of missing biomarker data, the analysis population for each outcome, or diagnostics for the paired t-test. It also does not report whether transformations, exclusions, or sensitivity analyses were used. These absences limit assessment of the statistical analysis but do not show that any particular method was or was not used.
The main methodological conclusion is narrow: the planned primary approach is described, but its result is unavailable because the assay did not demonstrate signaling. Details needed to assess the complete analysis, including a group-level contrast, uncertainty, missing-data handling, and multiplicity procedures, are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 13 outcome measures and 12 analyses. It names change in ACF pERK levels as the primary outcome and lists several secondary biomarker and concentration outcomes. However, it does not describe how the analyses map to the outcome measures, which comparisons were prespecified, or whether any hierarchy among outcomes was used. A multiplicity adjustment is not reported in the registry record.
As a general statistical matter, testing several outcomes or contrasts can increase the chance of at least one result appearing notable by chance. Interpretation can depend on whether outcomes are confirmatory or exploratory and on any planned adjustment or ordering of tests. The available record does not support a conclusion about how multiplicity was handled, so no such procedure should be assumed.
Missing-data details are also not reported in the registry record. There is no account of how many participants had usable measurements for each endpoint, how missing observations were handled, or whether sensitivity analyses were conducted. The primary endpoint itself was not reported because the assay did not demonstrate signaling; the record does not clarify whether this affected all samples or how the assay issue was assessed.
Analysis populations are not described. The registry record does not state whether analyses used all randomized participants, participants who received treatment, or a subset with available measurements. It also does not report exclusions after randomization or the handling of protocol deviations. Without these details, readers cannot assess whether the analyzed groups retained the balance created by randomization or whether results might depend on inclusion criteria.
These are reporting gaps, not evidence that a particular method was omitted. The statistical plan, missing-data procedures, and analysis populations are not reported in the registry record.
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 (25 mg) | 1 | 15 | 6.7% |
| Arm II (50 mg) | 0 | 15 | 0.0% |
| Arm III (100 mg) | 0 | 15 | 0.0% |
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 (25 mg) | 12 of 15 |
| Arm II (50 mg) | 13 of 15 |
| Arm III (100 mg) | 13 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm I (25 mg) | Arm II (50 mg) | Arm III (100 mg) |
|---|---|---|---|---|
| CHEST PAIN | Cardiac disorders | 1 of 15 | 0 of 15 | 0 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm I (25 mg) | Arm II (50 mg) | Arm III (100 mg) |
|---|---|---|---|---|
| DIARRHEA | Gastrointestinal disorders | 3 of 15 | 3 of 15 | 4 of 15 |
| DRY SKIN | Skin and subcutaneous tissue disorders | 3 of 15 | 2 of 15 | 5 of 15 |
| RASH | Skin and subcutaneous tissue disorders | 3 of 15 | 0 of 15 | 4 of 15 |
| FATIGUE | General disorders | 1 of 15 | 0 of 15 | 3 of 15 |
| NAUSEA | Gastrointestinal disorders | 2 of 15 | 2 of 15 | 0 of 15 |
| COUGH | Respiratory, thoracic and mediastinal disorders | 2 of 15 | 0 of 15 | 1 of 15 |
| DRY EYES | Eye disorders | 0 of 15 | 2 of 15 | 1 of 15 |
| RASH ON CHEST | Skin and subcutaneous tissue disorders | 1 of 15 | 0 of 15 | 2 of 15 |
| DIZZINESS | Nervous system disorders | 0 of 15 | 0 of 15 | 2 of 15 |
| DRY ITCHY EYE | Eye disorders | 2 of 15 | 0 of 15 | 0 of 15 |
Serious events with the highest arm-level rate: chest pain (6.7%).
The registry lists serious adverse events and other adverse events separately for each of the three dose groups. For serious adverse events, the record reports 1 affected participant in the 25 mg arm and 0 in each of the 50 mg and 100 mg arms; the listed number at risk is 15 in each group. For other adverse events, the recorded counts are 12, 13, and 13, respectively, with 15 at risk in each group. These are the registry's group-level figures and should be read as event reporting, not as a complete comparative safety analysis.
Chest pain is listed as a top serious adverse event term at 6.7%. The registry record does not state the arm attribution for this term in the registry record, nor does it provide details about the event's timing, severity, recurrence, or assessment of relationship to treatment. Death counts are not reported in the registry record.
In general, adverse event counts do not by themselves establish whether an intervention caused an event. Interpretation also depends on event definitions, ascertainment, duration of observation, and the clinical context. The record does not provide these details or a formal statistical comparison of safety across groups. The reported counts describe what was recorded, but they do not support a broad conclusion about comparative risk.
12. What the Result Does, and Does Not, Mean
The registry record shows that a randomized, triple-masked, parallel phase IIa study compared three daily oral erlotinib doses in patients with stage I-III colorectal cancer or adenoma. The primary endpoint was intended to measure change in ACF pERK levels from baseline to post-treatment, up to 30 days. The record states that the assay did not demonstrate signaling, and the primary change was not reported.
That missing primary result is the key limit on interpretation. There is no reported estimate, confidence interval, or p-value for the primary endpoint, and no quantitative comparison among the dose groups. The record therefore does not show the direction, magnitude, or precision of a primary biomarker effect. It also does not establish that there was no effect: a result not reported because the assay did not demonstrate signaling is not equivalent to an observed estimate of zero.
The endpoint was a biomarker measure, not a direct clinical outcome. Even a measurable change in a biomarker would not, by itself, establish an effect on recurrence, survival, symptoms, or other outcomes important to patients. The registry record does not report a clinical outcome result that would answer those questions.
Other biomarker and concentration outcomes are listed, but their numerical results are not present in the registry record for this analysis. They cannot be used to fill the primary endpoint gap. The adverse event counts offer a limited description of recorded events, but the registry record does not provide the detail needed to attribute events or make a robust comparison of safety.
The study is completed, yet completion status is not the same as a complete report of every result. The record does not report enough information about analysis populations, missing measurements, or multiplicity to reconstruct the full statistical analysis. The defensible interpretation is therefore descriptive: the trial's design and planned biomarker question are documented, while its primary endpoint result and several details needed for broader conclusions are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a planned endpoint and an interpretable endpoint result. The registry specifies a primary biomarker, a measurement method, a timeframe, and a paired t-test. It also reports that the assay did not demonstrate signaling, so the planned change is not reported. A statistical method cannot produce a meaningful treatment estimate when the underlying endpoint measurement is unavailable or not interpretable.
The distinction between within-participant change and differences among randomized groups is also important. A paired t-test can assess change between baseline and post-treatment measurements in the same participant. A question about whether dose groups differ requires an analysis that makes a between-group contrast. The registry record names the paired test but does not report a primary group comparison. Clear reporting of the estimand—the specific contrast being estimated—would help readers connect the design, analysis, and question.
The record also illustrates why outcome counts and statistical planning assumptions are not substitutes for results. Listing 13 outcome measures and 12 analyses does not clarify which tests were confirmatory or how multiplicity was handled. Planning illustrations based on fractions of an observed effect are not evidence of observed power and cannot establish that the study could detect a particular effect without the numerical planning details and underlying effect estimate.
Finally, safety counts and biomarker findings answer different questions. Adverse event figures describe recorded events, while the primary endpoint concerns a laboratory measure. Neither should be used as a proxy for the other. More complete reporting of estimates, uncertainty, analysis populations, missingness, and assay interpretation would allow readers to assess the strength and limits of the evidence more fully.
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 endpoint is not reported as a change because the assay did not demonstrate signaling. This prevents assessment of the magnitude and precision of the intended biomarker outcome. The registry record does not explain whether the assay issue affected every sample, whether repeat testing was performed, or how the failure to demonstrate signaling was determined.
The record does not report baseline characteristics, eligibility details beyond the listed conditions, or the method of randomization. It gives the triple-masked designation but does not identify which parties were masked or describe how masking was maintained. These omissions limit assessment of group comparability and potential sources of bias.
The primary analysis description names a paired t-test but does not report a between-dose comparison. No primary endpoint estimate, confidence interval, or p-value is available. The statistical approaches for the other outcomes, analysis populations, and any protocol deviations are not reported in the registry record. Nor are the amount and pattern of missing data, sensitivity analyses, or procedures for handling multiple outcomes.
The safety information is limited to group-level counts and a listed serious adverse event term. The registry record does not describe observation time, event definitions, event attribution, or the arm attribution of the chest pain term. Death counts are not reported in the registry record. These details are needed to interpret event counts in context.
The study's reported primary endpoint timeframe is up to 30 days, and the endpoint is a biomarker rather than a direct clinical outcome. The registry record does not provide a primary result that can be related to clinical outcomes, and the listed secondary outcomes do not include numerical results in the registry record. These limitations restrict conclusions to the design and reporting status rather than the efficacy or broader clinical implications of the intervention.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma — NCT00754494.
- Registry record last updated 2015-01-06; status last verified 2014-03.
- Results first posted 2015-01-06.
- 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
This completed, randomized, triple-masked, parallel phase IIa trial was sponsored by the National Cancer Institute (NCI). It enrolled 45 and studied daily oral erlotinib hydrochloride at 25 mg, 50 mg, or 100 mg in patients with stage I-III colorectal cancer or adenoma. The study started in 2008-07, with primary completion in 2012-10.
The primary endpoint was change in ACF pERK levels from baseline to post-treatment, up to 30 days, measured by Western blot and planned for analysis with a paired t-test. The registry record says the assay did not demonstrate signaling and does not report the primary change. Although 13 outcome measures and 12 analyses are listed, the available record does not provide the full statistical plan, analysis populations, missing-data methods, or multiplicity procedures.
The record lists serious and other adverse event counts for the three dose groups, but does not report enough context for a comparative safety assessment. Overall, the study design and endpoint are documented, while the primary biomarker result and key analysis details are not reported in the registry record.