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 S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib (NCT02134912), a randomized phase 2 study. The primary outcome is PFS Between Patients Randomized to Receive Pemetrexed Disodium Monotherapy Versus Crizotinib and Pemetrexed Disodium Combination Therapy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02134912 |
| Phase | Phase 2 |
| Condition | Adenocarcinoma of the Lung, Large Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | SWOG Cancer Research Network |
| Results posted | Yes |
2. Clinical Question
Population
Adults with ALK-positive non-squamous non-small cell lung cancer who had progressed systemically after previous clinical benefit from crizotinib monotherapy were the intended population. The listed conditions include stage IV and recurrent non-small cell lung cancer, adenocarcinoma of the lung, and large cell lung cancer. The primary-outcome population description states that the one patient who enrolled immediately withdrew consent. The registry record therefore contains no analyzable comparison for the intended population.
Intervention
One randomized arm was assigned crizotinib with pemetrexed disodium. The arm description states that crizotinib was taken by mouth twice daily on days 1–21 and pemetrexed was given intravenously on day 1.
Comparator
The other arm received pemetrexed disodium intravenously on day 1. The record states that patients in this arm could cross over to the combination arm after disease progression or symptomatic deterioration.
Primary question
The intended comparison was progression-free survival between pemetrexed monotherapy and the combination of crizotinib with pemetrexed. The primary endpoint counted time from registration to first documentation of progression or symptomatic deterioration, or death from any cause. The registry record reports no endpoint observations or treatment-effect estimate, so it cannot establish how the arms compared.
3. Trial Design
This was a randomized phase II trial sponsored by SWOG Cancer Research Network. Its official title describes a comparison of crizotinib plus pemetrexed with pemetrexed monotherapy in ALK-positive non-squamous non-small cell lung cancer after systemic progression following previous clinical benefit from crizotinib. The study was unmasked, and its design included crossover. The record does not report the allocation ratio or further details about the randomization procedure.
The combination arm received crizotinib by mouth twice daily on days 1–21 and pemetrexed intravenously on day 1. The comparator arm received pemetrexed intravenously on day 1. Patients assigned to pemetrexed alone could cross over to the combination arm after disease progression or symptomatic deterioration. The record does not report how crossover was handled in the planned primary analysis.
The study start is listed as 2014-08, and primary completion is listed as 2016-09. Its status is terminated. The registry record says that one patient enrolled and immediately withdrew consent, having enrolled the day before the study closed. It also states that no manuscript will be forthcoming. Thus, the planned randomized comparison did not produce a reported treatment-effect analysis in the record.
Secondary outcomes named in the record include response rates in each treatment arm, adverse events with the combination, patterns of failure, and overall survival. The record lists no analysis results for these outcomes. It also includes laboratory biomarker analysis and a pharmacological study as interventions, but does not report findings from those activities.
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: There is only one patient enrolled in this study. Patient was taken off study treatment by treating physician due to recent changes in standard of care. And patient never started protocol treatment. Thus we didn't enter any results for this only patient in the trial.
Overall Study
| Stage | Arm I (Crizotinib, Pemetrexed Disodium) | Arm II (Pemetrexed Disodium) |
|---|---|---|
| STARTED | 0 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The one patient that enrolled immediately withdrew consent \[enrolled the day before the study closed\]. No manuscript will be forthcoming.
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.
Population: The one patient that enrolled immediately withdrew consent \[enrolled the day before the study closed\]. No manuscript will be forthcoming.
| Characteristic | Unit | Arm I (Crizotinib, Pemetrexed Disodium) | Arm II (Pemetrexed Disodium) | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | |
| Age, Categorical: <=18 years | — | — | — | |
| Age, Categorical: Between 18 and 65 years | — | — | — | |
| Age, Categorical: >=65 years | — | — | — | |
| Sex: Female, Male: Female | — | — | — | |
| Sex: Female, Male: Male | — | — | — | |
| Region of Enrollment: United States | participants | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as PFS Between Patients Randomized to Receive Pemetrexed Disodium Monotherapy Versus Crizotinib and Pemetrexed Disodium Combination Therapy, measured over From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years.
| 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 progression-free survival (PFS), measured from registration until the first documented disease progression or symptomatic deterioration, or death from any cause. The stated assessment timeframe was up to 3 years. This definition treats worsening disease, symptomatic deterioration, and death as events, rather than requiring death alone.
General: A time-to-event endpoint such as PFS can capture how long participants remain without a defined event. It can be useful when the clinical question concerns disease control over time, and it allows the timing of events to contribute to the comparison. Interpreting such an endpoint depends on consistent event definitions, follow-up, and rules for handling participants whose event status is not observed by the end of follow-up.
The planned comparison was between the randomized treatment arms. The endpoint description identifies the events and time origin, but the registry record does not report participant-level follow-up, event counts, estimates of PFS, or a comparison result. The one enrolled participant immediately withdrew consent. Consequently, the record does not support an estimate of PFS in either arm or a conclusion about the relative timing of events.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized phase II trial designed to compare PFS for pemetrexed alone with PFS for crizotinib plus pemetrexed in ALK-positive non-squamous non-small cell lung cancer after systemic progression following previous clinical benefit from crizotinib. It does not report a result for that comparison. The primary-outcome fields contain no numerical estimate, event count, confidence interval, or test result.
The record states that one patient enrolled and immediately withdrew consent, enrolling the day before the study closed. The study is marked terminated, and the record says no manuscript will be forthcoming. This context is essential: the absence of a reported difference is not evidence that the treatments had the same outcome. Rather, there is no reported trial comparison from which to estimate a difference or assess its precision.
The planned primary analysis was a stratified log-rank test at the 0.10 level. That is a description of the intended test, not a reported test result. No p-value is listed, and no analysis count is recorded. The record does not identify the stratification factors, report whether the planned test was carried out, or give an estimate of the treatment effect. The 0.10 level should therefore not be read as a finding or as evidence that a result met a threshold.
The adverse-event fields list zeros for both arms, including the fields for participants at risk, serious events, other events, and deaths. Since the record also describes only one enrollment followed by immediate consent withdrawal, these entries do not provide an informative safety comparison. They should not be interpreted as evidence that either regimen had no adverse events among treated participants.
Other named outcomes include response rates, adverse events, patterns of failure, and overall survival. No results for these outcomes are reported. Without outcome data, the registry record cannot establish the direction, size, or precision of an efficacy or safety difference. Any planning illustrations based on an observed effect should also be interpreted cautiously: the record provides no observed treatment effect from this trial to anchor such an illustration.
9. Statistical Methods Explained
The record specifies a stratified log-rank test at the 0.10 level for the primary comparison of PFS between the two randomized arms. It does not report a completed analysis or its result. The methodological points below explain the stated approach in general terms and distinguish that plan from findings that are absent from the registry record.
What a log-rank test addresses
General: A log-rank test compares the event experience of groups over follow-up. For PFS, the event is defined in the record as progression or symptomatic deterioration, or death from any cause. Rather than reducing follow-up to a simple count of participants with an event, the test uses the ordering of events and the participants still under observation at event times. Its interpretation relies on appropriate follow-up and on the test's assumptions for comparing the groups over time.
The registry record says the proposed test was stratified. General: Stratification can account for specified participant groupings when comparing event experience, by making comparisons within strata and combining information across them. The record does not name any stratification factors, explain how they were chosen, or say how the strata would be incorporated into the analysis. Those implementation details are not reported in the registry record.
What the stated significance level means
The planned test used a 0.10 significance level. General: A significance level is a threshold for judging how incompatible the observed data would be with a specified null hypothesis under the test's assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. Because the registry record contains no test statistic or p-value, the stated threshold cannot be used to characterize the trial's result.
A test result alone would not fully describe the treatment contrast. General: An effect estimate indicates the magnitude and direction of a comparison, while a confidence interval conveys the range of values compatible with the data under the method used. Neither an effect estimate nor an interval is reported for this trial. With no reported endpoint observations, precision cannot be assessed.
Time-to-event follow-up and censoring
General: In time-to-event analyses, some participants may not experience the endpoint during observed follow-up. Their event time is then not known; their follow-up contributes information up to the last time they were known to be event-free. This is commonly handled through censoring, which requires assumptions about why follow-up ended. The registry record does not report censoring rules, follow-up completeness, or participant-level event and follow-up data. It therefore cannot show how these issues were addressed.
The endpoint timeframe is described as assessment up to 3 years. That timeframe does not itself give the amount of observed follow-up or establish that participants were followed for that duration. The record does not provide PFS estimates at particular times, event counts, or information about participants who may have been censored.
Planning illustrations and observed evidence
The registry record describes a sample-size illustration framework based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It distinguishes time-to-event illustrations, which use a total number of events, from other illustrations, which use participants per arm. These are planning assumptions, not evidence that the trial enrolled a sufficient sample or achieved a stated power. The record does not report an observed effect for this comparison or numerical sample-size illustration results. The sole enrollment and immediate withdrawal also leave no reported treatment comparison from which to estimate an effect.
General: Power calculations describe how often a design would be expected to detect a specified effect under chosen assumptions if the study were repeated. They do not give the probability that a particular trial result is true, and a calculation based on an observed effect is not an observed-power result. In this case, no effect estimate is reported to interpret, and the record does not provide its own sample-size justification.
Protocol and analysis details not reported
The registry record does not report the analysis population, handling of crossover in the primary analysis, missing-data methods, interim analyses, or a detailed statistical analysis plan. It does not identify the stratification factors or state whether the planned test was performed. These omissions prevent assessment of whether the completed conduct matched the planned method. The record gives a planned primary test, but the enrollment information and lack of results mean that no statistical inference about treatment differences can be drawn from it.
10. Multiplicity, Missing Data and Analysis Populations
The registry record names a primary endpoint and several secondary outcomes, including response rates, adverse events, patterns of failure, and overall survival. It does not report a multiplicity strategy for evaluating these outcomes. The planned primary test is described, but the record does not explain how the possibility of multiple comparisons would be handled or whether secondary outcomes were intended to be confirmatory or descriptive.
General: When several outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. Statistical plans may address this through a prespecified testing sequence or other adjustment, or may clearly label secondary analyses as exploratory. The registry record does not report which approach, if any, was planned. Since no outcome analyses are reported, there are no findings from which to assess the practical impact of multiplicity.
The record says that the one patient enrolled immediately withdrew consent. It does not state whether any data were retained, what data were available, or how missing outcomes would have been handled. It also does not define an intention-to-treat, per-protocol, or other analysis population. The primary-outcome population description reiterates the withdrawal, but does not specify an analysis set.
These omissions matter because an analysis population and rules for incomplete follow-up can affect a time-to-event comparison. General: Prespecified methods help clarify which randomized participants contribute to each analysis and how event-free follow-up is treated. No such details are reported for this trial. Given the single enrollment and immediate withdrawal, the registry record offers no basis for evaluating missing-data methods, population definitions, or multiplicity control in practice.
11. What the Result Does, and Does Not, Mean
The registry record establishes the trial's intended question and design, but it does not report an efficacy or safety result. It describes a randomized phase II comparison of pemetrexed alone against crizotinib plus pemetrexed, with PFS as the primary endpoint and crossover permitted from the monotherapy arm after progression or symptomatic deterioration.
The record reports one enrollment and says that the participant immediately withdrew consent on the day before the study closed. It also states that no manuscript will be forthcoming. No PFS estimate, event count, confidence interval, p-value, response result, or overall-survival result is reported. There is therefore no posted estimate of the effect of either assigned regimen relative to the other.
This absence should not be interpreted as showing no difference, equivalence, or lack of benefit. Those interpretations require data and an analysis capable of estimating the comparison with meaningful precision. Nor do zeros in the adverse-event fields establish that treatment was free of adverse events: the record does not provide an informative account of treatment exposure or a safety analysis.
General: A randomized design is intended to support comparisons between assigned groups, but randomization alone does not create an interpretable result when outcome information is unavailable. The design can describe what the study set out to compare; it cannot substitute for observations, follow-up, and analysis.
Accordingly, the most defensible reading is narrow: the registry records the planned treatment comparison, the endpoint definition, and the fact that enrollment ended after one participant withdrew consent. It does not support a clinical conclusion about relative PFS, response, overall survival, or adverse events.
12. Why This Trial Matters Statistically
This trial is statistically notable because it illustrates the difference between a randomized design and an informative randomized comparison. The registry record specifies the treatment arms, the PFS endpoint, and a planned stratified log-rank test. Yet one participant enrolled and immediately withdrew consent, and no primary-outcome analysis is reported. A clearly stated design does not by itself yield an estimate of treatment effect.
The record also shows why outcome definitions and analysis plans are only part of the evidence. PFS is defined using progression or symptomatic deterioration, or death, and the record states a timeframe of up to 3 years. For an actual comparison, readers would also need event information, follow-up, and results that indicate both effect size and precision. None of these results is reported.
The crossover option raises an additional design consideration. The monotherapy arm could cross over after progression or symptomatic deterioration. General: Crossover can affect how later outcomes are interpreted because participants may receive the other treatment after the initial comparison period. The registry record does not report how crossover would have been handled in the primary analysis, and the absence of outcome results means its impact cannot be assessed.
Finally, the record distinguishes planning from evidence. It describes assumptions for sample-size illustrations, but no observed treatment effect or numerical illustration result is reported. Such assumptions cannot be treated as trial findings or as evidence that a target sample was reached. The central statistical lesson is that an analysis plan and a completed, adequately observed comparison are different things; in this record, the former is described and the latter is not reported.
13. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation is that the registry record reports only one enrolled participant, who immediately withdrew consent. The study is marked terminated, and no manuscript will be forthcoming. As a result, the record contains no reported primary endpoint result and cannot support an estimate of PFS in either arm or a comparison between the arms.
Several details needed to assess the intended analysis are not reported in the registry record. These include the allocation ratio, randomization procedures, stratification factors, analysis population, crossover handling in the primary analysis, censoring rules, missing-data methods, interim analyses, and the detailed statistical analysis plan. The record states that a stratified log-rank test at the 0.10 level was planned, but does not say whether it was performed.
The registry lists secondary outcomes, but does not report their results or a multiplicity strategy. It also gives zero values in the adverse-event fields for both arms, without a usable account of exposure or a reported safety analysis. Those fields cannot establish the absence of adverse events among treated participants.
The endpoint timeframe of up to 3 years does not provide actual follow-up duration, and no event counts, effect estimates, or confidence intervals are reported. The record's sample-size illustration assumptions are not accompanied by numerical results or an observed effect. These limitations are specific to this trial record and leave the planned clinical comparison unanswered by the posted data.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib — NCT02134912.
- Registry record last updated 2020-02-20; status last verified 2020-02.
- Results first posted 2019-05-01.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
17. Record Summary
NCT02134912 was a randomized, unmasked phase II trial with a crossover design, sponsored by SWOG Cancer Research Network. It planned to compare pemetrexed disodium alone with crizotinib plus pemetrexed for ALK-positive non-squamous non-small cell lung cancer after systemic progression following previous clinical benefit from crizotinib. PFS was the primary endpoint, and a stratified log-rank test at the 0.10 level was planned.
The study began in 2014-08, had primary completion listed as 2016-09, and is marked terminated. The registry record states that one patient enrolled and immediately withdrew consent, and that no manuscript will be forthcoming. No primary or secondary outcome results are reported. The record therefore describes the intended comparison but does not provide an estimate of efficacy or a useful safety comparison.