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 Subsequent Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer (NCT03662074), a na phase 2 study. The primary outcome is Number of Participants With Positive Responses to Therapy Per Response Evaluation Criteria in Solid Tumors (RECIST).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03662074 |
| Phase | Phase 2 |
| Condition | Small Cell Lung Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wake Forest University Health Sciences |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced small cell lung cancer, including metastatic disease, who had received other treatments that failed. The registry record lists small cell lung carcinoma and stage IV lung cancer classifications.
Intervention
Gemcitabine and nivolumab. Participants received both drugs intravenously on day 1, with treatment repeating every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Comparator
There was no concurrent control group. The planned primary comparison was against a historical benchmark objective response rate of 10%, rather than against participants assigned to another treatment.
Primary question
How many participants had a positive response to therapy under RECIST, defined as complete or partial response, up to 8 weeks? The registry describes a one-sample test of proportion for comparison with the historical benchmark, but does not report the response count or test result.
This is a question about response observed in a treated group, not a randomized comparison of treatments. A response count could describe how often complete or partial responses were recorded in this study sample. By itself, it would not establish that the combination caused those responses or that it performs better than another treatment. The historical benchmark supplies a reference for the planned statistical comparison, but it is not a concurrently enrolled control group.
The registry record frames the study as a phase II pilot of subsequent-line treatment after other treatments had failed. Its description identifies response within the stated follow-up period as the primary endpoint. Overall survival, progression-free survival, and adverse events appear among the secondary outcome measures. The primary response result itself is not reported in the registry record, so the central clinical question cannot be answered from the posted results described there.
3. Trial Design
This was a phase II pilot study of gemcitabine and nivolumab for advanced small cell lung cancer. The registry lists a single-group model, no allocation, and no masking. Participants therefore received the listed treatment combination without a randomized assignment to a concurrent comparison group. The registry lists enrollment of 14 and identifies Wake Forest University Health Sciences as the sponsor.
The treatment description states that gemcitabine was given intravenously over 30 minutes and nivolumab intravenously over 60 minutes on day 1. Treatment was scheduled to repeat every 2 weeks for up to 4 courses, provided there was no disease progression or unacceptable toxicity. These are the treatment conditions stated in the record; it does not report how many participants received each planned course or their individual treatment exposure.
The study began on 2018-11-07, and the primary completion date is listed as 2020-10-07. Its status is terminated. The reason for termination, and whether termination changed the planned conduct or analysis, is not reported in the registry record. The record does not report a detailed protocol or a sample-size justification.
The primary endpoint was the number of participants with positive responses under RECIST, assessed up to 8 weeks. The stated comparison was a one-sample test of proportion against a historical response benchmark of 10%. This design can assess whether the study sample's response proportion differs from a reference value under the chosen statistical procedure. It cannot provide the same protection against differences in patient characteristics, follow-up, or care that a concurrent randomized control group is intended to provide. The record does not report the primary response count or the result of the planned comparison.
Secondary outcomes listed include overall survival, progression-free survival, and adverse events. The registry lists six secondary outcome measures and one analysis, but does not provide a detailed statistical analysis plan in the record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Treatment (Gemcitabine, Nivolumab) |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
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 | Treatment (Gemcitabine, Nivolumab) |
|---|---|---|
| Participants analysed | 14 | |
| Age, Continuous | years | 60.8 (SD 8.9) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 14 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 12 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Positive Responses to Therapy Per Response Evaluation Criteria in Solid Tumors (RECIST), measured over Up to 8 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with a positive response to therapy under RECIST. The record defines objective response as complete response or partial response. Complete response means disappearance of all target lesions; partial response means a decrease of at least 30% in the sum of the longest diameters of target lesions. The endpoint timeframe is up to 8 weeks.
RECIST provides standardized categories for describing tumor response. The registry also describes stable disease and progressive disease: stable disease does not meet the criteria for complete response, partial response, or progressive disease; progressive disease includes an increase of at least 20% in the sum of the longest diameters of target lesions or the appearance of one or more new lesions. It separately defines response in non-target lesions. These definitions specify how the endpoint is classified, but do not show which classifications participants received.
A count of participants with complete or partial response gives a direct description of the frequency of those outcomes in the study group. The planned comparison with a historical benchmark of 10% frames that count against a reference proportion using a one-sample test. Such a comparison does not substitute for a concurrent control group. The primary response count, estimated response proportion, uncertainty interval, and test result are not reported in the registry record. The endpoint definition therefore can be described, but the registry record does not establish the study’s observed response result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a small, single-group phase II pilot study and specifies a primary response endpoint, but it does not report the primary response count or the result of its planned comparison with the historical benchmark of 10%. Consequently, the posted results described in the registry record do not establish how many participants had a complete or partial response, how large the estimated response proportion was, or how uncertain that estimate may be.
The design matters when interpreting any response estimate. In a single-group study, the treated participants’ outcomes can be described, but there is no concurrent randomized group to show what would have happened under a different treatment or under the same conditions without the study combination. A historical benchmark is a reference value, not a group enrolled alongside the study participants. Differences between the study sample and the historical population, or between the circumstances in which outcomes were assessed, can influence such a comparison. These are general limitations of historical comparisons.
The registry lists enrollment of 14. This indicates the recorded enrollment, not the number with evaluable response data. The record does not state how many participants were assessed for the primary endpoint, whether any response assessments were missing, or how missing assessments were handled. It also does not provide an analysis population definition. Therefore, the enrollment figure should not be treated as the denominator for a response rate without further information.
The registry lists secondary outcome measures for overall survival and progression-free survival in both participant-count and time units, as well as adverse events. It does not give the survival estimates, follow-up details, or analysis methods for those outcomes in the registry record. Safety figures are listed separately: serious adverse events affected 1 of 14 at risk, other adverse events affected 11 of 14 at risk, and 8 deaths are recorded. Those counts do not establish that the treatment caused the events or deaths, and the record does not provide details about causes or timing.
The trial status is terminated, but the reason is not reported in the registry record. Termination alone does not explain whether the study stopped for operational, safety, efficacy, or other reasons. It should not be used as evidence for or against the treatment. Taken together, the record supports a description of the design, planned endpoint, treatment schedule, and reported safety counts. It does not report enough primary outcome information to characterize the observed response or draw a comparative conclusion.
9. Statistical Methods Explained
The primary analysis is described as a one-sample test of proportion. In general, this method evaluates whether a proportion estimated from one study group is compatible with a specified reference proportion, according to a statistical model and test procedure. Here, the registry identifies the historical benchmark as 10% and defines the study outcome as positive response under RECIST. The record does not report the test statistic, p-value, confidence interval, or response count, so the outcome of that planned comparison is not reported in the registry record.
What does a one-sample proportion test address?
In general, a proportion is the share of an analyzed group meeting a defined binary outcome. For this study, the binary outcome is whether a participant had a complete or partial response within the stated timeframe. A one-sample test compares the study group’s response proportion with a fixed reference value. It does not compare outcomes across two groups enrolled in the same trial, and it does not estimate a randomized treatment effect.
A test result, if reported, would be interpreted in relation to the null value and the statistical assumptions used. A p-value describes how compatible the data are with the null model; it is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. An interval estimate, if reported, would show a range of values compatible with the data and the specified method. The registry record does not report either type of inferential result for the primary endpoint.
Why does the historical benchmark need context?
As a general matter, a historical benchmark is informative only to the extent that it represents a relevant comparison for the current study. Differences in participant eligibility, prior treatment, assessment procedures, follow-up, or other study conditions can make a historical group unlike the enrolled study group. Since the registry describes no concurrent control group, the planned comparison cannot remove those potential differences through random assignment. The record does not report the source or further characteristics of the historical benchmark beyond its value of 10%.
The RECIST definitions make the endpoint more reproducible by setting rules for classifying target and non-target lesions. The registry specifies complete and partial response, stable disease, and progressive disease, including changes in lesion measurements and new lesions. These criteria define what counts as response; they do not tell readers whether assessments were complete, whether reviewers were independent, or how disagreements were handled. Those details are not reported in the registry record.
How should planning calculations be read?
Sample-size illustrations are planning calculations, not observed power. The stated assumptions describe two-sided significance level 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’s study design is single-group, so those equal-allocation assumptions describe the planning illustrations rather than the trial’s actual allocation. A planning calculation indicates what sample size might be needed under its assumptions; it does not establish the probability that this completed study detected an effect, nor does it change the uncertainty in the observed data.
In general, calculations that depend on an observed effect can be sensitive to the estimate used. When a study estimate is imprecise, using it as a planning input can yield a planning target that is also uncertain. The record does not provide the numerical outputs of the planning illustrations or the trial’s own sample-size justification. The illustrations should therefore not be interpreted as the study’s prespecified design rationale or as evidence about its findings.
What can the safety counts establish?
Counts of participants with events describe how many people in the stated group were recorded as affected. They do not, without further information, establish event rates over a defined exposure period or determine whether an event was caused by treatment. For time-to-event outcomes such as overall survival and progression-free survival, analysis ordinarily needs to account for follow-up and censoring; those methods and results are not reported in the registry record. The general statistical distinction is that a count, a proportion, and a time-to-event estimate answer different questions. The posted record’s outcome labels alone do not supply the underlying analyses.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six secondary outcome measures, including overall survival, progression-free survival, and adverse events. It also lists one analysis, but does not report enough detail to identify the full set of statistical tests, their order, or how the primary and secondary outcomes were handled together.
When a study examines multiple outcomes or performs multiple tests, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include prioritizing a primary outcome, adjusting the testing procedure, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, so it is not possible to determine from the record whether or how the analysis addressed this issue.
The record does not report how missing primary response assessments were handled, whether participants without an assessment were included in the analysis, or which analysis population was used. It does not report imputation procedures, rules for excluding participants, or sensitivity analyses for missing data. Enrollment of 14 does not establish that all enrolled participants contributed to every outcome analysis.
For the survival outcomes, the record does not describe censoring rules, follow-up completeness, or the analysis population. For adverse events, it does not give detailed event-collection methods or exposure time. These details affect interpretation of estimates and counts, but are not reported in the registry record. Accordingly, the posted information supports a limited description of listed outcomes and recorded counts, not a full assessment of the analysis strategy.
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 |
|---|---|---|---|
| Treatment (Gemcitabine, Nivolumab) | 1 | 14 | 7.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Gemcitabine, Nivolumab) | 8 of 14 |
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 |
|---|---|
| Treatment (Gemcitabine, Nivolumab) | 11 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Gemcitabine, Nivolumab) |
|---|---|---|
| Hyponatremia | Metabolism and nutrition disorders | 1 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Gemcitabine, Nivolumab) |
|---|---|---|
| Lung infection | Infections and infestations | 2 of 14 |
| Diarrhea | Gastrointestinal disorders | 1 of 14 |
| Fecal incontinence | Gastrointestinal disorders | 1 of 14 |
| Gastrointestinal pain | Gastrointestinal disorders | 1 of 14 |
| Nausea | Gastrointestinal disorders | 1 of 14 |
| Vomiting | Gastrointestinal disorders | 1 of 14 |
| Fatigue | General disorders | 1 of 14 |
| Fever | General disorders | 1 of 14 |
| Syncope | Nervous system disorders | 1 of 14 |
| Bronchopulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders | 1 of 14 |
Serious events with the highest arm-level rate: hyponatremia (7.1%).
The registry reports one treatment group, titled Treatment (Gemcitabine, Nivolumab). Serious adverse events were recorded for 1 of 14 participants at risk; other adverse events were recorded for 11 of 14 at risk. The record lists 8 deaths. Hyponatremia appears among the top serious adverse event terms at 7.1%.
These are descriptive registry counts. The record does not state the timing or causes of the deaths, nor does it establish whether an adverse event was judged related to treatment. The count of deaths should not be interpreted as a treatment effect or as a complete survival analysis. Likewise, the category of other adverse events should not be assumed to describe severity beyond the record’s classification.
The registry does not provide detailed event definitions, exposure-adjusted rates, event timing, or a comparison group for safety. The serious adverse event count, other adverse event count, and listed hyponatremia percentage address different summaries and should not be treated as interchangeable. In a single-group study, these figures describe what the registry records for participants in the treatment group; they do not by themselves determine causation or comparative safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase II pilot study evaluated gemcitabine and nivolumab in a single group of participants with advanced small cell lung cancer. It identifies a primary endpoint based on complete or partial response under RECIST, specifies a historical benchmark of 10%, and describes a one-sample test of proportion. It also records safety counts and secondary outcomes of interest.
However, the registry record does not report the primary response count, response proportion, confidence interval, or test result. It therefore does not show whether the study group’s response proportion differed from the benchmark, or how precisely a response estimate was measured. Without those results, the primary efficacy finding cannot be characterized from the record.
Even if a response result were available, the single-group design and historical comparison would limit causal interpretation. A comparison with a historical value is not equivalent to randomization against a concurrent control group. General differences in participants, treatment context, assessment, or follow-up can affect the comparison. The record does not provide the information needed to evaluate those potential differences in detail.
The record’s safety counts should also be read descriptively. They do not establish that gemcitabine or nivolumab caused an event or death, and the record does not report timing or causes. The study’s terminated status is recorded, but the reason is not reported; termination should not be taken as evidence of either benefit or harm.
Thus, the posted information describes the study’s question, design, treatment schedule, and selected safety summaries, but does not provide the primary response result needed to assess the central endpoint. It cannot support a conclusion that the treatment does or does not work.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its primary question combines a clearly defined binary response endpoint with a single-group design and a historical reference. The endpoint definitions specify which RECIST outcomes count as positive responses, while the planned one-sample proportion test describes how the study intended to compare its group with the benchmark of 10%. Those choices frame the analysis, but do not replace the need to report the observed count and its uncertainty.
The design also illustrates why the form of a comparison matters. A historical benchmark can offer context, but it is not a concurrent control group. A response proportion in one group is a description of that group; a difference from a historical value is sensitive to how well the benchmark matches the study population and conditions. The registry record does not give enough detail about the benchmark to assess that match.
The record further demonstrates the distinction between enrollment and an outcome denominator. Enrollment is listed as 14, but the number assessed for response and the handling of missing assessments are not reported. Without an explicit analysis population and outcome data, readers cannot infer the response proportion from enrollment alone.
Finally, the trial’s terminated status and the listed safety counts require restraint in interpretation. The reason for termination is not reported, and the safety summaries do not establish causation. Statistically, careful separation of study design, outcome definitions, analysis methods, and observed results is essential. In this case, the record describes the planned primary analysis but does not report the primary result, leaving the central statistical question unresolved.
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 most direct limitation for interpreting efficacy is that the primary response result is not reported in the registry record. The record specifies the endpoint and planned comparison but does not state the number of participants with complete or partial response, the analysis denominator, or the inferential result. The endpoint is described as being assessed up to 8 weeks, but the record does not give participant-level assessment completeness or follow-up details.
The study used a single-group model with no allocation and no masking. There was no concurrent control group, and the planned reference was a historical benchmark. This limits what can be inferred about comparative outcomes and makes the interpretation dependent on the relevance of that historical value. The record does not report its source or enough characteristics to assess comparability.
The registry lists enrollment of 14, but does not report the analysis population, missing-data procedures, or whether all enrolled participants were evaluable for each outcome. It also does not provide a detailed statistical analysis plan, a multiplicity strategy, or the trial’s sample-size justification. The reason for the terminated status is not reported in the registry record.
For safety, the posted counts do not include event timing, causes of death, exposure-adjusted summaries, or a concurrent comparison. For survival outcomes, the record lists outcome measures but does not report estimates or analysis details. These limitations restrict conclusions to the study design and the descriptive information actually recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Subsequent Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer — NCT03662074.
- Registry record last updated 2026-08-03; status last verified 2026-07.
- Results first posted 2021-11-12.
- 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 pilot study of gemcitabine and nivolumab for advanced small cell lung cancer. It lists a single-group design, no masking, enrollment of 14, and terminated status. Treatment was administered intravenously on day 1 and repeated every 2 weeks for up to 4 courses, subject to disease progression or unacceptable toxicity.
The primary endpoint was the number of participants with positive RECIST responses up to 8 weeks. The planned one-sample comparison used a historical benchmark of 10%, but the primary response result is not reported in the registry record. Listed safety information includes serious adverse events affecting 1 of 14 at risk, other adverse events affecting 11 of 14 at risk, 8 deaths, and hyponatremia at 7.1% among the top serious event terms. The reason for termination and detailed analysis methods are not reported.