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 Molecular Profiling in Lung Cancer Patients (NCT00191308), a non-randomized phase 2 study. The primary outcome is High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00191308 |
| Phase | Phase 2 |
| Condition | Non-Small Cell Lung Cancer, Carcinoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Participants had operable non-small cell lung cancer. The registry record says enrollment stopped early because of a lack of eligible participants, when 30 participants had enrolled. Tumor samples were collected in only 19 participants.
Intervention
The study used pemetrexed combined with cisplatin as neoadjuvant chemotherapy before radical non-small cell lung cancer surgery. The regimen description specifies pemetrexed at 500 milligrams per square meter intravenously and cisplatin at 75 mg/m^2 intravenously every 21 days for 3 cycles unless disease progression occurred. The brief summary describes 2 or 3 cycles.
Comparator
There was no separate control group. The registry describes a single-group, non-randomized study with no masking. Participants therefore were not assigned to a randomized comparison between the drug combination and another treatment.
Primary question
The primary objective was to assess selected molecular markers in tumor tissue and hypermethylated genes in peripheral blood at baseline, Cycle 2, and surgery. The study sought to explore whether marker levels or changes were linked to response to pemetrexed and cisplatin. The registry record says tumor-tissue analyses were not done because of the small sample size; a primary outcome result is not reported in the registry record.
This is chiefly a molecular-profiling and safety question, not a controlled estimate of treatment benefit. The listed marker assays include immunohistochemistry, polymerase chain reaction, and methylation-specific polymerase chain reaction. The clinical question asks whether these biological measurements could be related to participants’ response, while the listed secondary outcomes include objective tumor response, duration of response, disease-free survival, and overall survival. The record does not report estimates for those outcomes.
3. Trial Design
The registry identifies NCT00191308 as a Phase 2 study of pemetrexed plus cisplatin in operable lung cancer. It was non-randomized, unmasked, and used a single-group model. Those features matter for interpretation: there was no concurrent randomized control group, and the study was not designed as a like-for-like comparison between treatment arms.
The listed enrollment was 30. The record states that enrollment stopped early because of a lack of eligible participants. Tumor samples were collected in only 19 participants. The registry gives the study start as 2005-05, primary completion as 2008-07, and status as completed.
The arm description specifies pemetrexed at 500 milligrams per square meter intravenously every 21 days and cisplatin at 75 mg/m^2 intravenously every 21 days, for 3 cycles unless disease progression occurred. The brief summary describes neoadjuvant treatment for 2 or 3 cycles. Radical non-small cell lung cancer surgery is also listed as an intervention. The primary outcome timeframe includes baseline, Cycle 2, and surgery 4-8 weeks after the last pemetrexed dose.
The design combines molecular measurements with clinical and safety outcomes. The primary outcome concerns selected molecular markers in tumor tissue and hypermethylated genes in peripheral blood. Listed secondary outcomes are objective tumor response, duration of response, disease-free survival, and overall survival. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or interim analyses. It also lists no analysis entries. The posted information therefore supports description of the intended study question and recorded outcome availability, but not a complete assessment of how outcomes were statistically analyzed.
Because all participants received the study regimen in a single group, changes over time or observed outcomes cannot be separated from other influences using a randomized control comparison. The design can describe what was recorded among participants in the study, but it does not establish a comparative treatment effect.
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 + Cisplatin |
|---|---|
| STARTED | 30 |
| COMPLETED | 29 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Pemetrexed + Cisplatin |
|---|---|
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: Due to lack of eligible participants, enrollment was stopped early when 30 participants were enrolled. Tumor samples were collected in only 19 of these 30 participants. Results obtained from analyses of a small number of available samples were considered to be of little scientific and medical relevance, and tumor-tissue analyses were not conducted.
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 + Cisplatin |
|---|---|---|
| Participants analysed | 30 | |
| Age Continuous | years | 55.94 (SD 8.214) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 29 |
| Race/Ethnicity, Customized: Caucasian | participants | 30 |
| Region of Enrollment: Poland | participants | 30 |
| Basis for Diagnosis: Histopathological | participants | 30 |
| Basis for Diagnosis: Cytological | participants | 0 |
| Initial Pathological Diagnosis: Adenocarcinoma of Lung | participants | 2 |
| Initial Pathological Diagnosis: Mixed Cell Carcinoma of Lung | participants | 0 |
| Initial Pathological Diagnosis: Squamous Cell Carcinoma of Lung | participants | 20 |
| Initial Pathological Diagnosis: Large Cell Carcinoma of Lung | participants | 0 |
| Initial Pathological Diagnosis: Bronchoalveolar Carcinoma | participants | 0 |
| Initial Pathological Diagnosis: Other | participants | 8 |
| Stage of Disease at Study Entry: Stage IB | participants | 18 |
| Stage of Disease at Study Entry: Stage IIA | participants | 2 |
| Stage of Disease at Study Entry: Stage IIB | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood, measured over Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled around high or low expression of selected molecular markers in tumor tissues and hypermethylated genes in peripheral blood. Its stated measurement unit is participants, and its timeframe is baseline, Cycle 2, and surgery 4-8 weeks after the last pemetrexed dose. The markers assessed in tumor tissue include thymidylate synthase, GARFT, EGFR, DHFR, DPD, FPGS, reduced folate carrier, alpha folate receptor, ERCC1, and FPGH. Hypermethylated genes were assessed by methylation-specific polymerase chain reaction.
Such measurements can be used to describe biological characteristics and explore whether marker levels or changes are associated with clinical response. In general, repeated measurements can distinguish a baseline measurement from a later measurement, but they do not by themselves establish that a marker causes a response or that changing the marker changes an outcome.
The registry record says tumor-tissue analyses were not done because of the small sample size. It also states that tumor samples were collected in only 19 participants and that analyses of a small number of available samples were considered of little scientific and medical relevance. A numerical primary outcome result, including participant counts by marker category or a comparison of marker changes, is not reported in the registry record. Therefore the endpoint’s intended measurement can be described, but its result cannot be quantified from the registry information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive feature is that the study was a single-group investigation without randomization or masking. All enrolled participants were in the Pemetrexed + Cisplatin group. There is no separate control group in the registry record, so the study does not provide a randomized comparison against another regimen or against no study treatment. Any clinical outcome observed in the group cannot be attributed to the drug combination through a between-group estimate.
The primary outcome was molecular profiling rather than a reported treatment-effect estimate. Its intended measurements covered selected markers in tumor tissue and hypermethylated genes in peripheral blood at specified timepoints. The record says that tumor-tissue analyses were not done because of the small sample size. Tumor samples were available from only 19 of the 30 enrolled participants. The registry record does not report numerical results for the primary outcome, so the direction, size, and precision of any marker-response relationship cannot be assessed.
The clinical outcomes listed as secondary outcomes are objective tumor response, duration of response, disease-free survival, and overall survival. Their outcome estimates are not reported in the registry record. There are no reported confidence intervals or p-values for these outcomes in the information available. Without estimates and measures of uncertainty, the precision of any clinical finding cannot be evaluated.
The safety record lists 4 participants with serious adverse events and 19 with other adverse events in the Pemetrexed + Cisplatin group. The registry also lists bronchopleural fistula at 6.7%, gastric ulcer at 3.3%, and post procedural haemorrhage at 3.3% among the top serious terms. These figures describe the entries recorded in the registry; they do not supply a randomized comparison or establish whether an event was caused by treatment. Deaths are not reported in the registry record.
The early stop and limited tissue availability constrain the molecular objective. Small or unavailable samples can reduce the information available for marker analyses and make any estimates less precise. The registry record does not report a statistical analysis plan, methods for handling missing measurements, or analysis populations. Accordingly, the posted record supports a cautious description of study design, sample availability, and recorded adverse-event counts, but not a firm conclusion about marker associations or comparative efficacy.
9. Statistical Methods Explained
Statistical methods help define what an estimate represents, how uncertain it is, and which comparisons its design can support. In this study, the design and the availability of outcome data place important limits on those interpretations.
What does a single-group design allow?
In general, a single-group study describes outcomes among participants receiving the study regimen. A randomized control group can help distinguish treatment-related differences from background changes and other influences, because assignment creates a structured comparison. This study was non-randomized and single-group, so there is no concurrent randomized comparison. The registry explicitly notes that its arms are not a like-for-like control comparison; the study record lists only the Pemetrexed + Cisplatin group.
Without a control group, a change in a laboratory marker or a clinical outcome cannot by itself show what would have happened to similar participants under another treatment. This is a design limitation, not a calculation problem that can be resolved by a statistical test. The absence of masking also means the study was unmasked, as recorded; masking status should be considered when interpreting outcome assessment, although the registry does not describe the procedures used to assess each outcome.
What do the molecular measurements represent?
The primary outcome concerns high or low expression of selected molecular markers in tumor tissues and hypermethylated genes in peripheral blood. The stated timepoints are baseline, Cycle 2, and surgery 4-8 weeks after the last pemetrexed dose. Immunohistochemistry was used for thymidylate synthase, GARFT, and EGFR; polymerase chain reaction was used for DHFR, DPD, FPGS, reduced folate carrier, alpha folate receptor, ERCC1, and FPGH. Hypermethylated genes were assessed by methylation-specific polymerase chain reaction.
In general, a marker measured at multiple timepoints can be described by its level at each time or by a change between measurements. Those summaries answer different descriptive questions. A relationship between a marker and response would require an analysis that links marker information to response information. Even when such a relationship is observed, association does not establish that the marker causes the response. The registry record says tumor-tissue analyses were not done because of the small sample size, and it does not report a numerical marker analysis. The details of any peripheral-blood analysis are not reported in the registry record.
How should uncertainty be read?
In general, a confidence interval describes a range of values compatible with the observed data under the assumptions of the analysis. A narrower interval indicates greater precision; a wider interval indicates more uncertainty. A p-value, when reported, addresses how compatible the data are with a specified null model, not the probability that a treatment works. Neither a confidence interval nor a p-value can replace a suitable comparison design or resolve missing outcome information.
The registry record does not report confidence intervals or p-values for the primary or secondary outcomes. It also lists no analysis entries. As a result, there is no posted numerical estimate whose precision can be assessed for the main molecular question or the listed clinical outcomes. The lack of such estimates should not be interpreted as evidence of no effect or no association; it means those results are not reported in the registry record.
What do the planning illustrations mean?
In general, a sample-size calculation describes how much information a planned study might need under assumptions about an effect, variability, significance level, allocation, and analysis method. It is a planning exercise, not a result from participants. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are based on a fraction of an observed effect. For time-to-event outcomes, the stated method concerns the total number of events; for other outcomes, it concerns participants per arm.
These are generic planning assumptions, not a design description for this single-group study. The registry record does not report that the trial itself used two-arm allocation, nor does it report a sample-size justification for this trial. Planning illustrations are not observed power and do not show whether the study could detect an effect. No numerical planning results are reported in the registry record.
What does the safety count measure?
The posted safety figures are counts of participants with recorded events in the treatment group, accompanied by percentages for the listed serious-event terms. In general, event counts can indicate how many participants were recorded as affected, while event totals can count repeated occurrences. The record's figures should be read according to their stated participant-based labels; they do not provide a causal comparison. Further detail on event timing, recurrence, or attribution is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study lists a broad molecular objective and several secondary clinical outcomes. The molecular objective includes multiple markers assessed using different laboratory methods, while the secondary outcomes include objective tumor response, duration of response, disease-free survival, and overall survival. When multiple outcomes or markers are examined, general statistical practice considers the risk that some apparent findings may arise by chance. Methods for controlling or interpreting multiplicity depend on the analysis plan and the intended claims.
The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a detailed statistical analysis plan. It also lists no analysis entries. It is therefore not possible to determine whether the analyses were intended to be confirmatory or exploratory, or how multiple marker comparisons would have been handled. The outcome list alone does not establish that each outcome was analyzed.
Missingness is also relevant. Tumor samples were collected in only 19 of the 30 participants, and the record says tumor-tissue analyses were not done because of the small sample size. The reason samples were unavailable for other participants, the amount of missing peripheral-blood data, and the handling of missing measurements are not reported in the registry record. In general, analyses based only on available samples can describe those samples but may not represent all enrolled participants if availability is related to participant or disease characteristics.
The analysis populations are not reported in the registry record. It is not specified whether analyses were planned for all enrolled participants, participants who received treatment, participants with available samples, or another defined group. Without those details and numerical outcome results, the extent of missing-data impact and the scope of any analysis cannot be evaluated.
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 + Cisplatin | 4 | 30 | 13.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pemetrexed + Cisplatin | 19 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Pemetrexed + Cisplatin |
|---|---|---|
| Bronchopleural fistula | Respiratory, thoracic and mediastinal disorders | 2 of 30 |
| Gastric ulcer | Gastrointestinal disorders | 1 of 30 |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pemetrexed + Cisplatin |
|---|---|---|
| Alanine aminotransferase increased | Investigations | 4 of 30 |
| Aspartate aminotransferase increased | Investigations | 4 of 30 |
| Weight increased | Investigations | 4 of 30 |
| Hyperkalaemia | Metabolism and nutrition disorders | 3 of 30 |
| Hypernatraemia | Metabolism and nutrition disorders | 2 of 30 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 30 |
Serious events with the highest arm-level rate: bronchopleural fistula (6.7%), gastric ulcer (3.3%), post procedural haemorrhage (3.3%).
The registry records 4 participants with serious adverse events and 19 participants with other adverse events in the Pemetrexed + Cisplatin group; each category has 30 participants at risk. These are participant counts, not a comparison of event rates between randomized groups. The registry lists bronchopleural fistula at 6.7%, gastric ulcer at 3.3%, and post procedural haemorrhage at 3.3% as the top serious adverse-event terms.
In general, a serious adverse event is a safety classification, while an adverse event is an event recorded during a study; the registry figures alone do not establish that an event was caused by the study drugs. The record does not report a control group, a causal assessment for these events, or details about timing and recurrence. The listed percentages should be read as recorded for the specific serious-event terms, not as a complete measure of overall risk or as a treatment comparison.
Deaths are not reported in the registry record. That is different from a reported count of zero. The safety entries therefore describe the recorded counts and listed terms but do not support conclusions about comparative safety or causation.
12. What the Result Does, and Does Not, Mean
This record documents a Phase 2 study of neoadjuvant pemetrexed plus cisplatin in operable non-small cell lung cancer, with a primary objective focused on molecular markers and secondary outcomes that included tumor response and survival. It also records safety information for the single treatment group. These details show what the study set out to investigate and what was entered in the registry.
The primary outcome cannot be interpreted as a reported biomarker finding. The registry says tumor-tissue analyses were not done because of the small sample size, and it does not report numerical results for the primary outcome. The clinical secondary outcomes are listed, but their estimates are not reported in the registry record. Consequently, the posted information does not quantify a marker-response association, tumor response, duration of response, disease-free survival, or overall survival.
The study’s non-randomized, single-group design does not support a randomized comparison with another treatment. The safety counts can be described for the treated group, but they do not show how those counts compare with a control group or prove that the regimen caused an event. The registry reports 4 participants with serious adverse events and 19 with other adverse events; deaths are not reported in the registry record.
These limitations do not make the registry record meaningless. It identifies the intended molecular question, the treatment schedule, the selected assays, the sample-availability constraint, and the recorded safety counts. But the record does not provide the estimates and analysis details needed to judge the size or precision of treatment effects or marker associations. The appropriate interpretation is therefore descriptive and bounded by what is recorded, rather than a conclusion about efficacy or a causal biomarker relationship.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how design and data availability shape what can be learned. Its central objective was molecular profiling linked to treatment response, but tumor samples were collected in only 19 participants and tumor-tissue analyses were not done because of the small sample size. A clearly stated scientific question does not ensure that the measurements needed to answer it will be available in sufficient quantity.
The single-group, non-randomized design also defines the limits of inference. It can describe the experience recorded among participants receiving the regimen, but it lacks the randomized comparator needed for a like-for-like treatment contrast. That distinction matters when reading clinical outcomes or safety counts: a count in one group is not a comparative effect.
The registry record further illustrates the difference between an outcome being specified and an outcome being reported with an estimate. Objective tumor response, duration of response, disease-free survival, and overall survival are listed as secondary outcomes, yet numerical results are not reported in the record. Likewise, the primary molecular endpoint is described, but no numerical primary analysis is reported. Without estimates and uncertainty measures, a reader cannot assess precision or the strength of an association.
Finally, the record makes sample availability and early stopping relevant to interpretation. The enrollment stopped early because of a lack of eligible participants, and the analysis details, missing-data methods, and analysis populations are not reported. Together, these features show why conclusions depend not only on the named endpoint but also on the study design, availability of measurements, and transparency of analysis reporting.
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.
Several limitations are specific to this study record. Enrollment stopped early because of a lack of eligible participants when 30 participants had enrolled. The registry does not report a sample-size justification for the trial, so the intended precision or power for its molecular objective cannot be assessed from the record.
Tumor samples were collected in only 19 participants, and the registry says tumor-tissue analyses were not done because of the small sample size. The reason samples were unavailable for the other participants, and the handling of missing measurements, are not reported in the registry record. The record also does not provide numerical results for the primary molecular outcome.
The study was non-randomized, unmasked, and single-group. There was no separate control group for a randomized comparison. This limits interpretation of clinical outcomes and safety counts as treatment effects. The record lists objective tumor response, duration of response, disease-free survival, and overall survival, but their numerical estimates are not reported in the registry record.
Detailed analysis methods, analysis populations, multiplicity handling, and interim analyses are not reported in the registry record. Deaths are also not reported. These omissions leave uncertainty about how outcomes were analyzed and which participants contributed to each analysis. The registry record therefore supports a description of the study and its recorded safety counts, but not a full statistical evaluation of its intended molecular or clinical questions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Molecular Profiling in Lung Cancer Patients — NCT00191308.
- Registry record last updated 2011-10-21; status last verified 2011-10.
- Results first posted 2010-04-20.
- 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
NCT00191308 is a completed Phase 2, non-randomized, unmasked, single-group study of pemetrexed plus cisplatin before surgery in operable non-small cell lung cancer. The registry gives enrollment as 30 and states that enrollment stopped early because of a lack of eligible participants. Tumor samples were collected in only 19 participants.
The primary outcome concerned selected molecular markers in tumor tissue and hypermethylated genes in peripheral blood. The registry says tumor-tissue analyses were not done because of the small sample size, and no primary numerical result is reported. Listed secondary outcomes were objective tumor response, duration of response, disease-free survival, and overall survival; their numerical results are not reported in the registry record.
The safety record lists 4 participants with serious adverse events and 19 with other adverse events. No randomized control group or analysis entries are reported. The registry gives the start as 2005-05, primary completion as 2008-07, and status as completed.