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 Platinum-Based Chemotherapy Plus Ramucirumab in Patients With Advanced NSCLC Who Have Progressed on First Line Anti-PD-1 Immunotherapy (NCT03904108), a na phase 2 study. The primary outcome is Number of Participants With Objective Response Per RECIST 1.1 as Assessed by Central Imaging.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03904108 |
| Phase | Phase 2 |
| Condition | Carcinoma, Non-Small-Cell Lung |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ROGER S KERESZTES MD |
| Results posted | Yes |
2. Clinical Question
The study asked whether platinum-based combination chemotherapy with ramucirumab could produce objective responses in patients with advanced non-small-cell lung cancer whose disease had progressed after first-line anti-PD-1 immunotherapy. It was a non-randomized phase II study, and its stated hypothesis was that prior immunotherapy might act as a chemo-sensitizer, with the addition of ramucirumab associated with higher response rates. That statement describes the investigators’ hypothesis, not a result established by the registry record.
Population
Patients with advanced non-small-cell lung cancer who had progressed on first-line anti-PD-1 immunotherapy. The study description also specifies evidence of progression and a maintained good performance status for eligible patients.
Intervention
Platinum-based doublet chemotherapy plus ramucirumab was the regimen posed in the study question. The intervention listing gives ramucirumab 10 mg/kg IV on day 1, every 3 weeks for 4 cycles.
Comparator
There was no concurrent comparator group. The registry identifies a single-group, non-randomized study, so it does not provide a like-for-like control comparison.
Primary question
How many participants had an objective response, defined as complete or partial response using the registry’s stated response criteria and central imaging assessment? The record says primary-endpoint data were not collected.
Because there is no comparator and no collected primary endpoint result, the record cannot establish whether the regimen changed response probability relative to another treatment or to what would otherwise have occurred. The clinical question is therefore identifiable, but its answer is unavailable from the posted outcome data.
3. Trial Design
This was a phase II, non-randomized, single-group study. The registry lists allocation as not applicable and masking as none. With no randomized allocation and no control arm, the design was intended to assess outcomes among participants receiving the study regimen rather than estimate a randomized treatment contrast.
The study description specifies platinum doublet chemotherapy plus ramucirumab for patients with advanced non-small-cell lung cancer after progression on first-line anti-PD-1 immunotherapy. The intervention details list ramucirumab 10 mg/kg IV on day 1, every 3 weeks for 4 cycles. The registry’s intervention listing names ramucirumab; it does not give further dosing details for the platinum doublet in the intervention record.
The planned enrollment description says up to 25 evaluable participants would be enrolled over a period of 2 years, with seven patients recruited at the first stage. The registry records actual enrollment of 3 and lists the study status as terminated. Its dates are start 2019-06-27 and primary completion 2020-07-27. These registry entries do not establish why the study terminated or whether its planned recruitment stages were completed.
A single-group phase II design can describe outcomes observed in participants who receive a regimen, but cannot by itself separate a treatment effect from other explanations, including the natural course of illness, participant selection, or changes in care. The record does not report a statistical analysis plan, a reason for termination, or details of any interim decision process.
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 | Ramucirumab |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Data were not collected
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 | Ramucirumab |
|---|---|---|
| Participants analysed | 3 | |
| Age, Customized: Age Range 58-66 years | participants | 3 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
| Race/Ethnicity, Customized: white,non-Hispanic | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Objective Response Per RECIST 1.1 as Assessed by Central Imaging, measured over ≥18 weeks, up to maximum of 12 months.
| 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 the number of participants with an objective response, assessed by central imaging. Objective response was defined as complete response or partial response as the best overall response, with response confirmed using the subsequent 6-weekly scan. The registry’s endpoint timeframe is at least 18 weeks, up to a maximum of 12 months.
In the endpoint description, complete response means disappearance of all target lesions. Partial response means at least 30% decrease in the sum of the longest diameter of target lesions. The description refers to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), while the endpoint title says RECIST 1.1. That difference in the record should be noted rather than resolved by assumption. The description names MRI as the assessment method.
In general, an objective-response endpoint records whether participants meet prespecified imaging criteria for tumor shrinkage. It provides a categorical outcome that can be summarized as a count or proportion when the relevant participant data are collected. Central imaging assessment is intended to apply the imaging criteria consistently. The record labels the endpoint population as “Data were not collected,” and contains no response count or estimate. Consequently, it supplies no observed primary-endpoint result to interpret.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the registry records actual enrollment of 3 but reports that primary-endpoint population data were not collected. There is therefore no posted objective-response count, response proportion, uncertainty interval, or analysis result for the primary question. The registry also lists 0 analyses. It is not possible to infer an efficacy estimate, the precision of an estimate, or whether any participant met the response definition from these entries.
The intended endpoint was an objective response assessed by central imaging, with confirmation using a subsequent 6-weekly scan. Its timeframe was at least 18 weeks, up to a maximum of 12 months. These are endpoint specifications, not evidence that the assessments were completed or that responses occurred. The title of the endpoint cites RECIST 1.1, whereas its descriptive text cites RECIST v1.0. The record does not explain this difference.
The study was a non-randomized, single-group phase II trial. Even if a response result had been posted, a single-group result would describe the participants observed under the study regimen; it would not provide a randomized estimate of the regimen’s effect compared with a concurrent control. Differences between the enrolled participants and any external group could affect comparisons. No external comparison is reported in the registry record.
Recruitment was limited relative to the plan described in the record: up to 25 evaluable participants were planned, and actual enrollment is recorded as 3. The record says the study was terminated, but does not state why. Neither the small recorded enrollment nor the terminated status should be treated as an explanation for the absence of endpoint data; the reason is not reported in the registry record.
The registry describes the investigators’ expectation that prior immune therapy might sensitize tumors to chemotherapy, and that adding ramucirumab could be associated with higher response rates. This is a rationale or hypothesis, not an observed statistical finding. Without collected response data, no conclusion about whether the hypothesis was supported can be drawn from the posted outcomes.
Serious adverse event entries are present, including a group with 3 participants at risk and 3 affected, and a reported death count of 1. These safety entries are distinct from the missing primary outcome and do not fill the gap in response data. Their interpretation also depends on the limited enrolled population and the registry’s event reporting, not on an inferred treatment comparison.
Overall, the posted record documents a study question, a design, a planned regimen and endpoint, limited enrollment, termination, and safety entries. It does not provide the primary response data needed to estimate the outcome of interest. This is an absence of a reported estimate, not evidence that the regimen did or did not produce responses.
9. Statistical Methods Explained
The registry identifies a single-group phase II study with no random allocation and no masking. In general, a single-group design describes outcomes among participants receiving a regimen. It does not create a concurrent control group, so it cannot directly estimate a treatment contrast protected by randomization. A result from such a design may be useful for describing outcomes in the enrolled group, but causal interpretation requires caution because patient characteristics, disease course, and other care may also influence observed outcomes.
What would an objective-response analysis describe?
The primary endpoint is a categorical response outcome: each participant is classified according to whether the best overall response meets the definition of complete or partial response. The record describes complete response as disappearance of all target lesions and partial response as at least 30% decrease in the sum of the longest diameter of target lesions. It also says that objective response is based on confirmed responses using the subsequent 6-weekly scan.
In general, a response analysis can report the number of participants meeting the response definition and the proportion among a clearly defined analysis population. A confidence interval communicates the range of values compatible with the observed data under the statistical model and its assumptions. It reflects uncertainty in an estimate; it does not guarantee that the true value lies within the interval. Neither a response count, a proportion, nor a confidence interval is reported for this trial’s primary endpoint, because the endpoint population is marked “Data were not collected.” No estimate should be reconstructed from enrollment alone.
Why does the missing control group matter?
Randomization, when used, tends to balance measured and unmeasured prognostic factors across treatment groups in expectation. This study was non-randomized and single-group, so there is no within-trial control comparison. Even a complete response summary would answer what was observed among the participants, not what would have happened to those same participants under an alternative regimen. Comparisons with a separate study or historical experience would need additional assumptions and are not reported in the registry record.
The study description states a hypothesis about prior immunotherapy acting as a chemo-sensitizer and higher response rates with chemotherapy plus ramucirumab. Statistical testing of that hypothesis would require an outcome estimate and a defined reference or comparison. The registry does not report a primary-endpoint analysis, an analysis plan, or a comparison result. Accordingly, no test statistic or p-value can be interpreted.
How should the planning illustrations be understood?
The registry’s planning assumptions describe illustrations computed from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect; time-to-event calculations use a total event count, while other calculations refer to participants per arm. These are planning conventions, not a description of the actual trial design. The study itself is listed as single-group, and the primary endpoint data were not collected. Any sample-size illustrations should therefore not be interpreted as evidence of observed power, a completed treatment comparison, or a sample-size justification used by the investigators. The registry does not report the trial’s own sample-size justification.
More generally, power calculations depend on a target effect, variability or event assumptions, an analysis method, and a chosen significance level. A planning calculation describes what a proposed design might detect under those assumptions. It does not measure the probability that a result from a completed study is true, and it cannot compensate for an unreported outcome. Here, the assumptions are explicitly described as planning illustrations rather than the trial’s own design, and the record supplies no primary response estimate on which to base an interpretation.
What does the record allow readers to assess?
The design entries permit a description of the study structure: phase II, non-randomized, single group, and unmasked. The enrollment entry records 3 participants. The outcome entry defines the intended objective-response measure and its assessment window, but identifies the population data as not collected. The registry lists 0 analyses. These registry entries distinguish what was planned or specified from what was actually analyzed and posted.
The endpoint title says RECIST 1.1, while the descriptive text says RECIST v1.0. In general, a protocol should specify the criteria applied to classify response, because a change in criteria can affect outcome definitions. The record does not explain the discrepancy, so it is not possible to determine from the posted information which version governed assessment. Likewise, no details are reported about how missing response assessments would have been handled, the analysis population intended for the primary endpoint, or any adjustment for multiple analyses.
These method concepts help identify the evidence required for an efficacy interpretation: collected endpoint observations, a defined analysis population, a specified analysis, and an appropriate account of uncertainty. The registry record does not contain those primary-endpoint results. Statistical methods can explain what such results would mean in general, but cannot supply an estimate where the outcome data are absent.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 0 analyses and states that data for the primary objective-response population were not collected. No primary endpoint estimate or inferential result is posted. A missing outcome result is not a null finding: it does not show that the response rate was zero, nor does it establish that a response target was met.
Multiplicity concerns arise when a study assesses several outcomes, subgroups, time points, or statistical comparisons, because repeated opportunities to identify a result can affect interpretation of statistical evidence. The record lists 2 outcome measures, but it does not report an analysis plan, a testing hierarchy, or a multiplicity adjustment. Whether any such procedures were planned is not reported in the registry record. The description of seven patients recruited at the first stage does not establish that a formal interim analysis or decision rule was used.
The registry does not specify the primary endpoint analysis population beyond stating “Data were not collected.” It also does not report how incomplete imaging, unconfirmed responses, withdrawals, or other missing outcome data would be handled. No assumptions about missingness or imputation methods should be inferred. Without participant-level outcome availability and a stated analysis population, the denominator for an objective-response estimate cannot be established from the outcome entry.
These limitations restrict interpretation independently of the single-group design. Even if safety information is available, it does not replace missing efficacy data. The reasons for missing primary-endpoint data, the intended analysis approach, and whether any unreported analyses were conducted 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 |
|---|---|---|---|
| Ramucirumab | 3 | 3 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ramucirumab | 1 of 3 |
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 |
|---|---|
| Ramucirumab | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Ramucirumab |
|---|---|---|
| pneumonia | Infections and infestations | 2 of 3 |
| Neutropenic fever | Infections and infestations | 1 of 3 |
| bronchial occlusion | Respiratory, thoracic and mediastinal disorders | 1 of 3 |
| respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ramucirumab |
|---|---|---|
| neutrophil count decreased | Blood and lymphatic system disorders | 3 of 3 |
| fatigue | General disorders | 3 of 3 |
| anemia | Blood and lymphatic system disorders | 2 of 3 |
| leukocytosis | Blood and lymphatic system disorders | 2 of 3 |
| sinus tachycardia | Cardiac disorders | 2 of 3 |
| anorexia | Metabolism and nutrition disorders | 2 of 3 |
| acidosis | Metabolism and nutrition disorders | 2 of 3 |
| hypotension | Cardiac disorders | 2 of 3 |
| mucositis | Gastrointestinal disorders | 2 of 3 |
| thrombocytopenia | Blood and lymphatic system disorders | 1 of 3 |
Serious events with the highest arm-level rate: pneumonia (66.7%), neutropenic fever (33.3%), bronchial occlusion (33.3%), respiratory failure (33.3%).
The registry’s adverse-event group for ramucirumab lists 3 participants at risk for serious adverse events and 3 affected. It also lists 3 participants at risk for other adverse events and 3 affected, and reports 1 death. These entries describe the registry’s safety reporting; they do not establish that an event was caused by the study regimen. The record does not provide a causal assessment in the entries.
The top serious adverse-event terms are pneumonia, 66.7%; neutropenic fever, 33.3%; bronchial occlusion, 33.3%; and respiratory failure, 33.3%. These are the percentages reported in the registry. The entries do not establish whether terms occurred in distinct participants or overlapped, and they should not be added together. With only 3 participants recorded as at risk, the safety summaries describe a small group and cannot characterize event frequency precisely across a broader population.
Serious adverse events and other adverse events are separate registry categories. The record’s safety entries should be read alongside its limited enrollment and missing primary endpoint data, not as a substitute for an efficacy result. Further details about event timing, individual participant courses, or attribution are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase II, non-randomized, single-group study was registered to examine platinum-based chemotherapy plus ramucirumab in advanced non-small-cell lung cancer after progression on first-line anti-PD-1 immunotherapy. It records actual enrollment of 3, a terminated status, and a primary objective-response endpoint assessed by central imaging. It also provides safety entries for the ramucirumab group.
The most important limit is that the registry says primary-endpoint data were not collected. There is no posted response count, response estimate, or uncertainty interval. Consequently, the record cannot show how many participants had a confirmed complete or partial response, nor can it establish whether the investigators’ response-rate hypothesis was supported. The absence of a result should not be interpreted as a finding of no response.
The single-group design also means that even a reported response estimate would not provide a randomized comparison with another treatment. The registry has no concurrent control arm, and it cannot isolate the regimen’s effect from other explanations for outcomes. The record does not report external comparison data or a statistical analysis plan.
Planning illustrations are not trial outcomes and are not evidence of observed power. They describe calculations under stated assumptions, whereas the clinical outcome data needed to interpret the primary endpoint are absent. Likewise, safety event listings can describe reported events in the enrolled group but cannot supply the missing efficacy result or establish causation.
The proper statistical conclusion is therefore limited: the study question and intended endpoint are documented, but the posted record does not contain the primary response data needed to estimate that outcome. The registry does not report why the study was terminated or why endpoint data were not collected.
13. Why This Trial Matters Statistically
This study is statistically informative in part because it illustrates the distinction between a planned clinical question and an answerable outcome record. The registry specifies an objective-response endpoint, its assessment approach, and a timeframe, but marks the endpoint population as data not collected. An endpoint definition alone is not an outcome estimate; the participant observations and analysis are essential to quantify what happened.
The design also matters. A non-randomized, single-group phase II study can be used to describe outcomes among participants receiving a regimen, but it cannot provide a like-for-like randomized treatment contrast. The record’s stated hypothesis about chemo-sensitization is scientifically distinct from evidence that would test the hypothesis. Without collected response outcomes, neither a descriptive response estimate nor a comparison is available.
Actual enrollment of 3 is notably different from the plan described as up to 25 evaluable participants, with seven patients at the first stage. These are separate details: planned enrollment does not represent observed enrollment, and a staged recruitment description does not by itself prove that interim statistical rules were applied. The study is recorded as terminated, but the reason is not reported in the registry record.
Finally, the record makes clear why statistical interpretation depends on transparent reporting of analysis populations, missing data, and analysis procedures. Those details are unavailable for the primary endpoint. Recognizing that limit avoids treating planning calculations, safety entries, or the study hypothesis as substitutes for missing efficacy results.
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 limitation is the absence of collected data for the objective-response endpoint. The record therefore offers no response count, proportion, or measure of precision. The registry also lists 0 analyses. The endpoint timeframe and response criteria describe the intended measurement but do not establish that the assessments were completed.
Actual enrollment was 3, while the study description planned up to 25 evaluable participants over a period of 2 years and described seven patients at the first stage. The study status is terminated. The registry does not give the reason for termination, whether the planned recruitment stages were completed, or why primary-endpoint data were not collected.
The single-group, non-randomized design has no concurrent control and cannot support a randomized treatment comparison. Masking is listed as none. In addition, the endpoint title specifies RECIST 1.1, but the descriptive text specifies RECIST v1.0; the record does not clarify which version was used.
The record does not report the primary analysis population, handling of missing assessments, an analysis plan, or whether multiplicity procedures were planned. The safety entries concern a very limited enrolled group and do not provide a comparative assessment. The registry also does not state whether the posted event percentages refer to overlapping participants or provide detailed event-level context. These limitations constrain both efficacy and safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Platinum-Based Chemotherapy Plus Ramucirumab in Patients With Advanced NSCLC Who Have Progressed on First Line Anti-PD-1 Immunotherapy — NCT03904108.
- Registry record last updated 2022-05-26; status last verified 2022-04.
- Results first posted 2022-05-26.
- 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
NCT03904108 is a phase II, non-randomized, single-group study of platinum-based chemotherapy plus ramucirumab in patients with advanced non-small-cell lung cancer who progressed on first-line anti-PD-1 immunotherapy. The intervention details list ramucirumab 10 mg/kg IV on day 1, every 3 weeks for 4 cycles. The primary endpoint was the number of participants with an objective response assessed by central imaging.
The registry records enrollment of 3 and status as terminated. It gives a study start date of 2019-06-27 and primary completion date of 2020-07-27. The primary endpoint population is marked “Data were not collected,” and 0 analyses are listed. The record also reports serious and other adverse-event entries, including 1 death. It does not report the reason for termination or provide a primary response result.