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 Rational EpigenetiC Immunotherapy for SEcond Line Therapy in Patients With NSCLC: PRECISE Trial (NCT02664181), a randomized phase 2 study. The primary outcome is Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST1.1).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02664181 |
| Phase | Phase 2 |
| Condition | Lung Cancer, Non-small Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Case Comprehensive Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants enrolled in a study of second-line therapy for non-small cell lung cancer. The primary outcome description defines its response population as all randomized subjects, while the endpoint population field says participants enrolled in the study; the record does not explain this distinction.
Intervention
Oral tetrahydrouridine (THU) followed by oral decitabine, given with nivolumab. The regimen description specifies oral THU at approximately 10 mg/kg, followed by oral decitabine at approximately 0.2 mg/kg 60 minutes later, twice weekly on consecutive days. Nivolumab is described as 3 mg/kg intravenously every two weeks until progression.
Comparator
Nivolumab alone, described in the registry record as standard of care for patients with non-small cell lung cancer who have progressed on prior chemotherapy. The regimen is nivolumab at 3 mg/kg intravenously every two weeks until progression.
Primary question
Does adding oral THU/decitabine to nivolumab change the objective response rate, defined by the proportion of randomized subjects whose best overall response is complete response or partial response under RECIST 1.1? The registry record does not present a single comparative estimate for this question.
This is a question about a response outcome, not a direct comparison of survival or time to progression. Those outcomes are listed as secondary outcomes, including long-term follow-up for overall survival. The registry record does not report a single summary of the primary endpoint that would quantify the difference between treatment groups. It therefore supports describing the trial question and endpoint definition, but not a conclusion about the relative response rates.
3. Trial Design
PRECISE, registered as NCT02664181, is a randomized, open-label, parallel-group phase II study. The registry reports enrollment of 13 participants and a completed status. The recorded study start was 2017-06-06, and primary completion was 2019-07-02. The sponsor is Case Comprehensive Cancer Center.
The experimental arm combined nivolumab with oral THU and decitabine. The regimen description says THU was followed by decitabine 60 minutes later, twice weekly on consecutive days, alongside nivolumab given intravenously every two weeks until progression. The comparator arm received nivolumab on the same stated schedule. The registry describes nivolumab as standard of care for patients with non-small cell lung cancer who had progressed on prior chemotherapy.
Randomized allocation means that assignment to the treatment groups was intended to be determined by chance. The record states that masking was none, so the trial was open label; it does not report blinding of participants or study personnel. A parallel design assigns participants to a study group rather than describing a crossover between regimens. The registry record does not report the allocation ratio, the randomization method, or whether any stratification factors were used.
The reported enrollment is a limited basis for estimating comparative effects, and small studies can yield imprecise estimates. The registry record does not report a sample-size justification or the statistical planning assumptions used when the trial was designed. Its completion status does not, by itself, establish what the results were or how complete the outcome reporting is.
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 | Oral THU/Decitabine + Nivolumab | Nivolumab |
|---|---|---|
| STARTED | 8 | 5 |
| COMPLETED | 8 | 5 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Participants enrolled in study
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: Participants enrolled in study
| Characteristic | Unit | Oral THU/Decitabine + Nivolumab | Nivolumab | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 5 | 13 | |
| Age, Customized: years – 40-49 | Participants | 2 | 0 | 2 |
| Age, Customized: years – 50-59 | Participants | 1 | 2 | 3 |
| Age, Customized: years – 60-69 | Participants | 3 | 2 | 5 |
| Age, Customized: years – 70-79 | Participants | 2 | 0 | 2 |
| Age, Customized: years – 80-89 | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Female | Participants | 4 | 3 | 7 |
| Sex: Female, Male: Male | Participants | 4 | 2 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 8 | 5 | 13 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 5 | 4 | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Region of Enrollment: United States | participants | 8 | 5 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST1.1), measured over Up to 52 weeks after beginning therapy.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is objective response by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). It is expressed as a count of participants, and the description defines the overall response rate as the proportion of all randomized subjects whose best overall response from baseline is either a complete response or a partial response.
Best overall response is determined from response designations recorded between randomization and objectively documented progression or subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations contribute to the determination. For those continuing treatment beyond progression, the definition uses response designations recorded at the time of the initial RECIST 1.1-defined progression.
Response endpoints are used to describe tumor change according to prespecified criteria. A proportion based on complete or partial response gives a direct summary of how many participants meet the stated response definition, rather than measuring how long participants live or how long it takes for progression. The registry lists time to progression and overall survival as secondary outcomes, not as the primary endpoint.
The timeframe is up to 52 weeks after beginning therapy. The endpoint definition is stated, but the registry record does not reduce the primary outcome's reported categories or time points to a single comparative result. Counts by response category, a treatment contrast, and its precision are therefore not available as a single summary in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies objective response by RECIST 1.1 as the primary endpoint and describes how best overall response is determined. It does not, however, provide a single comparative result for that endpoint. The posted outcome information is not reduced to one comparison across the reported categories or time points. Consequently, a numerical difference between the nivolumab group and the combination group, and the uncertainty around such a difference, cannot be characterized from the registry record.
This distinction matters because an endpoint definition is not itself an outcome result. Knowing that complete and partial responses count toward overall response rate explains what the trial intended to measure, but it does not show how many participants met that definition in either group. Without a reported group-level comparison and measures of precision, the direction and size of any response contrast remain unreported in the registry record.
The study was randomized and phase II, with enrollment of 13 participants. Randomization supports a planned comparison, but it cannot ensure that a small trial will produce precise estimates. A result based on few participants may be sensitive to the outcome of individual participants; this is a general statistical consideration, not a claim about a particular observed response in this trial. No confidence interval or primary-outcome p-value is reported in the information available for this analysis.
Time to progression, overall survival, and long-term overall survival are listed as secondary outcomes. Their names alone do not reveal the observed event counts, follow-up, estimates, or uncertainty. Those results are not reported in the registry record addressed here, so no inference about them is warranted from the endpoint list.
Safety reporting includes group-level counts for participants at risk, participants with serious adverse events, participants with other adverse events, and deaths. These are descriptive counts. They do not establish that an event was caused by treatment, and the record does not supply a comparative safety analysis or the definitions and follow-up details needed to interpret every count fully.
Overall, the record supports a description of the study design, the intended response measure, and the posted safety counts. It does not support a numerical statement about comparative efficacy or a conclusion that one regimen produced more responses than the other. Missing estimates should not be replaced with assumptions based on the study's purpose, design, or completion status.
9. Statistical Methods Explained
The registry record describes a randomized phase II comparison of nivolumab alone with oral THU/decitabine plus nivolumab. Randomization is a design method for assigning treatment by chance. In general, it helps make treatment groups comparable with respect to both measured and unmeasured characteristics, although it does not guarantee balance in a small study. The record does not report the allocation method, ratio, or any stratification details.
What does the primary endpoint measure?
The primary endpoint is objective response by RECIST 1.1. Its definition counts a participant as having an objective response when best overall response is complete response or partial response. The overall response rate is the proportion meeting that definition among the randomized subjects. The registry labels the outcome unit as participants and gives a timeframe of up to 52 weeks after therapy begins.
Best overall response is based on response designations in a specified observation window. The registry description sets the end of that window at objectively documented progression or subsequent anti-cancer therapy, whichever occurs first. If neither is documented, all available response designations contribute. If treatment continues beyond progression, the response designations at the initial RECIST 1.1-defined progression are used. These rules specify which observations contribute to the endpoint; they do not supply the observed response counts.
Why is a proportion useful?
As a general statistical concept, a proportion expresses the share of an analysis population meeting a binary definition. It is straightforward to interpret when the outcome definition and denominator are clear. A response proportion does not describe the timing of response, the duration of response, or survival. Those questions require different outcome summaries. In this trial, time to progression and overall survival are listed separately as secondary outcomes.
A comparison of response proportions would ordinarily need group-specific response results and a stated contrast, such as a difference or ratio, together with a measure of uncertainty. Those comparative results are not reported as a single summary in the registry record. No confidence interval or primary-outcome p-value is reported in the information, so neither statistical precision nor compatibility with a range of possible effects can be assessed from a single estimate.
What does uncertainty mean?
Generally, a confidence interval describes uncertainty around an estimate under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, but an interval does not remove limitations in study design or reporting. The registry record does not provide a confidence interval for a single primary-outcome comparison. It is therefore not possible to discuss the precision of that comparison using an interval.
Statistical significance is also not the same as clinical importance. In general, a p-value assesses how compatible data are with a specified null model, given the analysis assumptions; it does not measure the probability that a treatment works. No primary-outcome p-value or analysis method is reported. The statistical plan, including any adjustment or model used for the primary endpoint, is not reported in the registry record.
How should the planning illustrations be read?
The planning illustrations use the observed effect as a reference and consider detecting a stated fraction of that effect. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. These are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. They should not be read as estimates of the trial's achieved ability to detect an effect.
Sample-size planning depends on choices about the target effect, significance level, allocation, and analysis method. In general, planning estimates are conditional on those assumptions; changing them can change the number of participants needed. The registry record does not report the trial's own sample-size justification or establish that the later planning illustration reproduces the original design calculation. No calculated planning values are stated in the record information.
The safety counts are descriptive. A count of participants with an event does not by itself describe event timing, recurrence, severity beyond the serious-versus-other classification, or causality. Comparative interpretation also depends on consistent definitions and observation periods. Those additional details are not reported in the registry record. The listed serious-event terms and percentages should therefore be read as registry descriptions, not as adjusted treatment comparisons.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome title, objective response by RECIST 1.1, and secondary outcomes of time to progression, overall survival, and long-term overall survival. It also indicates that the primary outcome information includes several categories or time points and is not reduced to a single comparison. The record does not report a multiplicity strategy for interpreting several outcomes, categories, or time points. Without such a strategy, the registry information does not establish how any statistical testing across outcomes was controlled or prioritized.
The record does not report a statistical analysis plan for missing outcome data, including how participants without evaluable response assessments were handled. It does not state whether missing observations were imputed, excluded, or addressed through another method. Those details are important because a proportion depends on its analysis population and on how unavailable outcomes are treated.
The primary outcome definition says the overall response rate is based on all randomized subjects. The endpoint population field instead describes participants enrolled in the study. The registry record does not explain how those population descriptions relate to the analysis used for the posted results. It also does not report a distinct intention-to-treat or per-protocol analysis definition.
For the secondary outcomes, the available record lists outcome names but does not provide the analysis populations, censoring rules, missing-data procedures, or statistical methods. These omissions limit interpretation of those outcomes. The absence of these details should be treated as unreported information, not as evidence that no methods were used.
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 |
|---|---|---|---|
| Oral THU/Decitabine + Nivolumab | 4 | 8 | 50.0% |
| Nivolumab | 1 | 5 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Oral THU/Decitabine + Nivolumab | 6 of 8 |
| Nivolumab | 3 of 5 |
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 |
|---|---|
| Oral THU/Decitabine + Nivolumab | 8 of 8 |
| Nivolumab | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Oral THU/Decitabine + Nivolumab | Nivolumab |
|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 8 | 1 of 5 |
| Neutrophil count decreased | Investigations | 2 of 8 | 0 of 5 |
| Chronic obstructive pulmonary disease exacerbation | Respiratory, thoracic and mediastinal disorders | 0 of 8 | 1 of 5 |
| dehydration | Metabolism and nutrition disorders | 1 of 8 | 0 of 5 |
| Dizziness | Nervous system disorders | 1 of 8 | 0 of 5 |
| Edema Limbs | General disorders | 0 of 8 | 1 of 5 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 8 | 0 of 5 |
| Fever | General disorders | 1 of 8 | 0 of 5 |
| Hypotension | Vascular disorders | 1 of 8 | 0 of 5 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 8 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Oral THU/Decitabine + Nivolumab | Nivolumab |
|---|---|---|---|
| anemia | Blood and lymphatic system disorders | 6 of 8 | 2 of 5 |
| Fatigue | General disorders | 5 of 8 | 1 of 5 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 3 of 8 | 2 of 5 |
| anorexia | Metabolism and nutrition disorders | 3 of 8 | 1 of 5 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 8 | 1 of 5 |
| hyponatremia | Metabolism and nutrition disorders | 2 of 8 | 2 of 5 |
| lymphocyte count decreased | Investigations | 3 of 8 | 1 of 5 |
| White blood cell decreased | Investigations | 4 of 8 | 0 of 5 |
| Alkaline phosphatase increased | Investigations | 3 of 8 | 0 of 5 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 8 | 1 of 5 |
Serious events with the highest arm-level rate: neutrophil count decreased (25.0%), chronic obstructive pulmonary disease exacerbation (20.0%), dyspnea (20.0%), edema limbs (20.0%), dehydration (12.5%).
For the Oral THU/Decitabine plus Nivolumab group, the registry reports 8 participants at risk for serious adverse events, 4 affected by serious adverse events, 8 at risk for other adverse events, 8 affected by other adverse events, and 6 deaths. For the Nivolumab group, it reports 5 participants at risk for serious adverse events, 1 affected by serious adverse events, 5 at risk for other adverse events, 5 affected by other adverse events, and 3 deaths. These are the registry's counts; they are not an adjusted comparison.
The serious-event terms listed include neutrophil count decreased at 25.0%, chronic obstructive pulmonary disease exacerbation at 20.0%, dyspnea at 20.0%, edema limbs at 20.0%, dehydration at 12.5%, and dizziness at 12.5%. The registry information does not specify a group attribution for each listed term, so those percentages should not be assigned to a particular arm.
Counts of participants with events do not show whether events were caused by treatment. The registry record does not report the event definitions, timing, recurrent-event counts, or details that would explain the deaths or establish their relationship to study treatment. These figures are descriptive safety information, not proof of causation or a complete safety comparison.
12. What the Result Does, and Does Not, Mean
The registry record establishes the intended comparison: nivolumab alone versus oral THU/decitabine with nivolumab in a randomized phase II study of second-line therapy for non-small cell lung cancer. It also provides a primary endpoint definition based on best overall response under RECIST 1.1. These details clarify the scientific question and what would count as a response.
They do not establish the observed comparative response result. The primary outcome information is not reduced to a single comparison across its reported categories or time points. No single treatment contrast, confidence interval, or p-value for that endpoint is reported in the registry information used. Therefore, the size, direction, and precision of a response difference cannot be stated from this record.
The study's completed status means the registry lists it as completed; it does not by itself tell readers what the findings were. Likewise, the trial purpose describes what investigators intended to assess, not what the observed data demonstrated. A treatment rationale or mechanism in the study description is not a substitute for comparative outcome evidence.
The safety information gives counts of participants with serious and other adverse events and counts of deaths. Such counts can help describe what the registry recorded, but they do not establish causation or provide a complete comparison of risks. The record does not report enough context to interpret every safety count as a treatment effect.
In general, conclusions from a clinical trial depend on the outcome estimates, their uncertainty, the analysis population, missing-data methods, and the prespecified analysis plan. Several of these elements are not reported in the registry record. The appropriate statistical reading is therefore limited: the design and endpoint can be described, and the posted safety counts can be stated, but comparative efficacy conclusions cannot be drawn from an unreported primary-outcome contrast.
13. Why This Trial Matters Statistically
This trial is statistically notable for the contrast between a clearly stated response question and the absence of a single reported comparative response estimate in the registry information. The objective response definition is detailed, including the RECIST 1.1 criteria and the rules for determining best overall response. Yet a detailed definition cannot answer the treatment question without group-level results and uncertainty measures.
The randomized, parallel-group phase II design sets up a direct comparison of nivolumab alone with the combination regimen. Enrollment of 13 participants makes precision an important consideration. In general, estimates from small studies can be strongly influenced by a small number of outcomes, and uncertainty should be assessed rather than inferred from a point estimate alone. Here, the registry record does not provide a single point estimate or interval for the primary comparison.
The record also illustrates why outcome lists and outcome results must be distinguished. Time to progression and overall survival are named as secondary outcomes, while the primary response endpoint includes categories or time points that are not consolidated into one comparison. Without the analysis plan and the corresponding results, readers cannot assess multiplicity handling or determine how the reported outcomes relate to a planned hierarchy.
Planning calculations have a different role from observed results. The stated planning assumptions describe an illustration based on an observed effect and specified design choices; they do not establish the trial's original sample-size rationale or its observed power. Keeping planning assumptions separate from outcome evidence is necessary for sound interpretation.
More broadly, this record shows why transparent reporting of group-specific estimates, denominators, analysis populations, missing-data methods, and uncertainty matters. Without those elements, a randomized design alone does not make the comparative result interpretable.
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.
A central limitation is that the primary endpoint is not presented as a single comparative result. The registry describes objective response and its assessment rules, but the outcome information is not reduced across its categories or time points to one treatment contrast. Group-level response counts and uncertainty for a single comparison are therefore not available in the registry record addressed.
Enrollment was 13, which limits the amount of information available for estimating effects. As a general statistical point, small studies often yield imprecise estimates, but no precision estimate for the primary comparison is reported. The registry record also does not report the original sample-size justification, so the intended design target cannot be evaluated.
The record identifies a randomized, open-label, parallel design, but it does not describe the randomization method, allocation ratio, or any stratification. It does not report a statistical analysis plan, multiplicity approach, missing-data method, or the analysis population used for posted results. The endpoint population field and the definition's reference to all randomized subjects are not reconciled in the registry record.
For secondary outcomes, the record lists time to progression and overall survival, including long-term follow-up, but does not provide their estimates or the details needed to interpret follow-up and analysis. Safety information consists of counts and a list of serious-event terms and percentages; attribution of those terms to arms and further event context are not reported in the information.
These limitations concern reporting and interpretability. They do not establish that analyses were not conducted, nor do they determine what the unreported outcomes were.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Rational EpigenetiC Immunotherapy for SEcond Line Therapy in Patients With NSCLC: PRECISE Trial — NCT02664181.
- Registry record last updated 2024-09-03; status last verified 2024-08.
- Results first posted 2020-12-10.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
PRECISE (NCT02664181) is a completed, randomized, open-label, parallel-group phase II trial sponsored by Case Comprehensive Cancer Center. It enrolled 13 participants and compared nivolumab alone with oral THU/decitabine plus nivolumab as second-line therapy for non-small cell lung cancer. The recorded study start was 2017-06-06, with primary completion on 2019-07-02.
The primary endpoint was objective response by RECIST 1.1, defined using complete or partial response as best overall response. Time to progression, overall survival, and long-term overall survival were listed as secondary outcomes. The registry record does not reduce the primary endpoint's categories or time points to a single comparative result, and it does not report a single treatment contrast with its precision.
Safety information includes counts of participants with serious and other adverse events and deaths in each group, along with listed serious-event terms and percentages. The registry information does not establish causality or provide all details needed for a comparative safety interpretation.