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 Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases (NCT03844750), a na phase 2 study. The primary outcome is Proportion of Patients With a >= 2-fold Increase in the Tumor-infiltrating Cells Per Unit Area (5 High Power Fields) in Post- Versus Pre Pembrolizumab Treatment Tumor Specimens..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03844750 |
| Phase | Phase 2 |
| Condition | Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Chloe Atreya, MD, PhD |
| Results posted | Yes |
2. Clinical Question
Population
Patients with colorectal cancer that had spread to the liver and could be removed surgically were the intended population. The brief summary describes treatment after standard-of-care chemotherapy. The listed conditions include stage IV colorectal cancer and metastatic malignant neoplasm in the liver.
Intervention
The study evaluated pembrolizumab and vactosertib in a treatment plan involving therapy before and after liver surgery. Hepatectomy was also listed as an intervention. The registry describes a neoadjuvant regimen, but the adjuvant regimen description is incomplete.
Comparator
There was no separate comparator arm: the design is recorded as single-group, with allocation listed as not applicable and masking as none. The study therefore does not provide a like-for-like control comparison of the intervention against another treatment or against no intervention.
Primary question
The primary endpoint asked what proportion of patients had at least a 2-fold increase in tumor-infiltrating immune cells per unit area in tumor specimens after versus before pembrolizumab treatment. The registry says the sponsor’s early termination of the study ended the funding needed for the planned endpoint analysis.
3. Trial Design
This was a phase II, single-group study of preoperative immunotherapy for patients with colorectal cancer and resectable hepatic metastases. The registry records enrollment of 6 and describes the study as terminated. Allocation is listed as not applicable, and masking as none. With no parallel control group, the design can describe outcomes among participants who received the study regimen but cannot make a randomized comparison with another treatment.
The brief summary describes pembrolizumab and vactosertib after standard-of-care chemotherapy, before liver metastases surgery, and after surgery. The listed interventions include pembrolizumab, vactosertib, and hepatectomy. The arm description specifies neoadjuvant pembrolizumab at a fixed dose of 200 mg intravenously for 1 cycle, alongside vactosertib 200 mg by mouth once daily, 5 days per week for 2 weeks. It also starts to describe adjuvant treatment, but that description is cut off in the registry record; the full regimen is not reported in the registry record.
The study’s stated primary outcome was a tissue-based measure rather than a direct comparison of survival or tumor response. Secondary outcomes listed in the record include adverse events, perioperative complications, R0 resection, pathologic response, objective response rate, and relapse-free survival. The registry lists a primary endpoint timeframe of up to 2 years. However, it states that early termination by the collaborating sponsor ended the funding available for the specific primary-endpoint analyses, and that no future funding plans currently exist for that analysis.
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 (Vactosertib, Pembrolizumab, Surgery) |
|---|---|
| STARTED | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Due to early study termination by the collaborating sponsor, the funds provided by the collaborating sponsor were no longer available to complete the specific analyses detailed in the primary endpoint. No plans currently exist to fund analysis of this endpoint in the future.
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 (Vactosertib, Pembrolizumab, Surgery) |
|---|---|---|
| Participants analysed | 6 | |
| Age, Customized: 40 - 49 years old | Participants | 1 |
| Age, Customized: 50 - 59 years old | Participants | 4 |
| Age, Customized: 60 - 69 years old | Participants | 1 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| 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 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Patients With a >= 2-fold Increase in the Tumor-infiltrating Cells Per Unit Area (5 High Power Fields) in Post- Versus Pre Pembrolizumab Treatment Tumor Specimens., measured over Up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns the proportion of patients whose tumor-infiltrating immune-cell count per unit area increased at least 2-fold in a post-pembrolizumab specimen compared with a pre-pembrolizumab specimen. The registry describes measuring these cells by immunohistochemistry and counting them per unit area across 5 high-power fields. It lists the timeframe as up to 2 years.
This endpoint is a tissue-based measure of change in immune-cell infiltration associated with treatment exposure. In general, measuring a biologic feature in paired pre- and post-treatment specimens can describe whether that feature changed within the sampled tumors. A proportion meeting a prespecified threshold can express how often that threshold was reached among the patients included in the analysis. It is not itself a direct measure of whether cancer recurred, whether surgery was successful, or whether patients lived longer.
The registry record says the collaborating sponsor’s early termination meant funds were no longer available to complete the analyses detailed in this endpoint, and that there are no current plans to fund the analysis in the future. Consequently, the primary endpoint result is not reported in the registry record. The endpoint definition is available, but the planned proportion and its statistical precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a small, single-group phase II study and gives an enrollment of 6. It also records the study status as terminated. The design and status matter for interpreting the posted information: there is no randomized comparator, and the record says the planned analysis of the primary endpoint could not be completed because sponsor funding ended after early termination.
The primary question was whether tumor-infiltrating immune cells increased by at least the stated threshold in post-treatment compared with pre-treatment specimens. The registry gives the method and timeframe for that endpoint, but it does not report the endpoint result. There is therefore no posted estimate of the proportion meeting the threshold, nor a confidence interval describing the precision of that estimate. Without those results, the primary endpoint cannot be interpreted as showing a particular degree of change.
The record does include safety counts for the treatment group. It lists 1 participant affected by a serious adverse event among 6 at risk, and 6 affected by other adverse events among 6 at risk. It records 0 deaths. Colitis is listed among the serious adverse-event terms at 16.7%. These are descriptive figures for the recorded group. They do not establish how the rates would compare with another treatment, because there is no control arm, and the registry does not provide a causal comparison.
The listed secondary outcomes include treatment-related adverse events, events of clinical interest, perioperative complications, R0 resection, pathologic response, objective response rate, and median relapse-free survival. Their presence as outcome names should not be mistaken for reported results. Outcome estimates and statistical analyses for these measures are not reported in the registry record.
In general, a confidence interval communicates the range of values compatible with an estimate under the analysis assumptions; wider intervals indicate greater uncertainty. No primary endpoint estimate or interval is reported, so the extent of statistical uncertainty around that endpoint cannot be assessed from the registry record. A single-group study can describe observed outcomes in its participants, but it cannot separate treatment effects from other explanations as a controlled comparison can.
9. Statistical Methods Explained
The registry describes the study’s design and endpoint, but does not report a statistical analysis for the primary endpoint. It states that the funding needed to complete the specified analyses was no longer available following early study termination. The record also lists no analyses. The following concepts explain how the stated endpoint and design would generally be interpreted; they are not claims about analyses carried out in this study.
What does the primary endpoint estimate?
The endpoint is a proportion: among the patients included in the relevant analysis, it would describe how many met the criterion of at least a 2-fold increase in tumor-infiltrating immune cells per unit area after versus before pembrolizumab treatment. The record specifies immunohistochemistry and a count per unit area across 5 high-power fields. The numerator would depend on the number of evaluable patients meeting the criterion, while the denominator would depend on which patients had the required specimen measurements and were included in the analysis. Those counts and the analysis population are not reported in the registry record.
In general, a proportion is a summary of how often a defined event occurs within a specified group. Its interpretation depends on a clear event definition and a clear denominator. For a paired tissue endpoint, both measurements must be available and sufficiently interpretable for the comparison to be made. The registry record does not report how missing specimens, unusable tissue, or incomplete measurements were to be handled.
Why does the single-group design matter?
The trial is recorded as single-group, with no masking and no allocation to a control arm. In general, a single-group study can describe outcomes observed among participants receiving the study regimen. It cannot directly estimate a treatment contrast against a concurrent control group. Changes between pre- and post-treatment specimens may be described, but that within-person comparison is not equivalent to a randomized comparison of treatment strategies. Other changes over time, specimen variation, and the characteristics of patients who contribute usable samples can affect interpretation.
Randomization, when used, is intended to make comparison groups more similar on average with respect to factors that could influence outcomes. Here there is no randomized control group to support that type of treatment-effect estimate. The registry record does not report a statistical adjustment strategy intended to address confounding or other differences from an external comparison.
What would precision measures add?
In general, a point estimate gives a single summary, while a confidence interval indicates the statistical uncertainty around that estimate under the chosen model and assumptions. For a proportion, precision depends in part on the number of evaluable observations and how many meet the endpoint definition. With a small study, estimates can be particularly sensitive to individual observations. No estimate, confidence interval, or inferential test for the primary endpoint is reported in the registry record.
General methods for proportions can use a model or interval procedure suited to binary outcomes. The appropriate choice depends on the analysis plan, the number of observations, and whether the endpoint is treated as a simple proportion or modeled with other factors. The registry does not report the method chosen for this endpoint, so a specific interval or model should not be attributed to the investigators.
How should planning illustrations be read?
Any sample-size planning illustrations associated with the posted results are not observed study outcomes and are not evidence of observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. The record says time-to-event planning uses a total number of events under the Schoenfeld method, while other planning values are participants per arm.
In general, such calculations explore how many observations a hypothetical study might require under specified assumptions. They do not describe the number of participants actually enrolled, prove that a study had adequate power, or recover an original protocol’s design rationale. The registry does not report the trial’s own sample-size justification or statistical plan. In addition, this study is single-group, so the equal-allocation, two-arm assumptions in a planning illustration do not describe the trial’s actual design.
What is not available for the primary analysis?
The primary endpoint description includes a timeframe of up to 2 years, but a timeframe alone does not establish when specimens were collected or analyzed for each participant. The registry record does not report the primary endpoint result, the analysis population, the handling of missing measurements, or an inferential method. It also does not report interim analyses or a detailed statistical analysis plan. These omissions limit assessment of the intended analysis and of the precision or robustness of any endpoint estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, spanning safety, surgical outcomes, tumor response, and relapse-free survival. When a study evaluates several outcomes, the chance of finding an apparently notable result can increase if each is tested separately without an appropriate analysis strategy. In general, multiplicity methods can control the overall false-positive risk or prioritize a prespecified endpoint hierarchy. The registry record does not report whether any such strategy was planned or used.
The primary endpoint is described, but its planned analysis was not completed because sponsor funding was no longer available after early termination. The endpoint result and its analysis population are not reported in the registry record. Results, analysis populations, and missing-data methods for the listed secondary outcomes are also not reported in the registry record. The record does not explain whether unavailable tissue, incomplete measurements, or participant withdrawal affected the endpoint data.
In general, missing outcome data can reduce precision and may bias an estimate if the probability of a missing measurement is related to the outcome or to participant characteristics. A statistical analysis should define which participants are included and how unavailable observations are handled. Those decisions cannot be inferred from the endpoint definition alone. The registry record does not report an intention-to-treat, per-protocol, or other named analysis population for the primary endpoint.
The record identifies the study as single-group and does not report a detailed statistical analysis plan. The protocol’s approach to multiplicity, missing data, analysis populations, or interim analyses is therefore not reported in the registry record. Without those details and without endpoint results, it is not possible to assess whether results across outcomes were analyzed under a prespecified inferential framework.
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 (Vactosertib, Pembrolizumab, Surgery) | 1 | 6 | 16.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Vactosertib, Pembrolizumab, Surgery) | 0 of 6 |
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 (Vactosertib, Pembrolizumab, Surgery) | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Vactosertib, Pembrolizumab, Surgery) |
|---|---|---|
| Colitis | Gastrointestinal disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Vactosertib, Pembrolizumab, Surgery) |
|---|---|---|
| Fatigue | General disorders | 3 of 6 |
| Headache | Nervous system disorders | 3 of 6 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 3 of 6 |
| Hypothyroidism | Endocrine disorders | 2 of 6 |
| Abdominal distension | Gastrointestinal disorders | 2 of 6 |
| Nausea | Gastrointestinal disorders | 2 of 6 |
| Hypercalcemia | Metabolism and nutrition disorders | 2 of 6 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 2 of 6 |
| Peripheral sensory neuropathy | Nervous system disorders | 2 of 6 |
| Acute kidney injury | Renal and urinary disorders | 2 of 6 |
Serious events with the highest arm-level rate: colitis (16.7%).
The registry lists one treatment group and reports 1 participant affected by a serious adverse event among 6 at risk. For other adverse events, it reports 6 affected among 6 at risk. The recorded number of deaths is 0. Colitis appears in the serious adverse-event terms at 16.7%. These are descriptive counts and a listed term; they are not comparative estimates against a control group.
In general, an at-risk count is the group used as the denominator for an adverse-event summary, while an affected count is the number recorded as experiencing the event category. Such summaries do not by themselves show event severity beyond the category stated, duration, recurrence, or whether an event was caused by treatment. The registry’s serious-event figure should not be read as a rate difference or relative risk, because no comparator arm is reported.
The record does not give additional detail in the safety figures about the clinical course of these events or the criteria used to attribute them to treatment. The listed secondary outcomes include treatment-related adverse events, events of clinical interest, and perioperative complications, but their outcome results are not reported in the registry record. The safety counts therefore describe only the posted summaries and do not establish a complete safety profile.
12. What the Result Does, and Does Not, Mean
The primary endpoint was designed to describe a tissue-level change: the proportion of patients with at least a 2-fold increase in tumor-infiltrating immune cells per unit area in post- versus pre-pembrolizumab specimens. The registry record does not report that proportion or its statistical precision. It also says the planned analysis could not be completed after the collaborating sponsor ended the funding needed for it. The endpoint’s biological rationale and measurement definition are not substitutes for an observed result.
The posted safety information gives descriptive figures for the single treatment group: 1 participant with a serious adverse event among 6 at risk, 6 with other adverse events among 6 at risk, and 0 deaths. Colitis is listed as a serious adverse-event term at 16.7%. These figures do not support a controlled comparison, and they do not show what would have happened under a different treatment strategy.
In general, an observed outcome in a single group can reflect the intervention, the underlying disease, other care, participant characteristics, and chance. A control group helps distinguish treatment-associated outcomes from these other influences, especially when allocation is randomized. This study’s design does not include such a comparator. The registry also does not report analysis results for the listed surgical, response, or relapse-free survival outcomes.
Accordingly, the registry supports a description of the study’s design, planned primary question, termination status, and posted safety counts. It does not provide a completed primary endpoint analysis or comparative evidence about treatment effects. The absence of a reported endpoint result should not be interpreted as evidence that the endpoint did or did not change; it means the result is not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates a central distinction in clinical research: defining an endpoint is not the same as reporting its result. The registry specifies a tissue-based primary question, including the comparison of pre- and post-pembrolizumab specimens and the threshold for an increase. It also states that the analysis could not be completed after sponsor funding ended. Without the endpoint estimate and its precision, readers cannot assess the observed pattern the study was designed to measure.
The design also affects what statistical conclusions would be possible. A single-group phase II study can provide descriptive information about participants who received the regimen, but it does not provide a randomized estimate of how outcomes differ from a control treatment. That limitation applies even when outcome definitions and measurement procedures are clearly stated. It is especially important when interpreting safety counts, because the record provides no concurrent comparison group.
The registry’s status and analysis information are relevant to research transparency. The study is recorded as terminated, and the primary endpoint population field explains that funding was unavailable for the specified analyses. Such context helps distinguish an endpoint that was planned from one for which an estimate was ultimately reported. The registry also lists clinically relevant secondary outcomes, but their results are not reported in the registry record.
More generally, this record shows why readers should consider study design, endpoint completion, analysis populations, missing-data handling, and precision together. A numerical count may be informative about what was recorded in the study group, while still being insufficient for a causal comparison. Clear separation of descriptive findings, planned questions, and unavailable analyses is essential to sound statistical interpretation.
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 study’s single-group design is a key limitation for causal interpretation. The record lists no comparator arm, allocation as not applicable, and no masking. Consequently, the posted safety counts cannot be contrasted with outcomes under another treatment within the study, and observed changes cannot be attributed to the regimen through a randomized between-group comparison.
The primary endpoint analysis was not completed according to the registry record because the collaborating sponsor’s early termination ended the funds available for the specified analyses. No current plans to fund that endpoint analysis are reported. The endpoint estimate, its precision, and the analysis population are therefore not available in the registry record. The record also does not describe how missing specimens or incomplete tissue measurements would have been handled.
The arm description is incomplete: it begins to describe adjuvant treatment but ends before giving the full regimen. The registry record does not report the full adjuvant schedule. Although the brief summary describes therapy before and after surgery, the incomplete details limit a full reconstruction of the planned treatment sequence from the record.
The registry lists secondary outcomes, but does not report their statistical results or a detailed analysis plan. It also does not report a sample-size justification, interim analyses, or a plan for multiplicity. The enrollment is recorded as 6, which limits the amount of descriptive information available, but no precision estimate for the primary endpoint is reported. These limitations mean that the record supports only a constrained account of study design and posted safety summaries, not a completed analysis of the primary clinical question.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases — NCT03844750.
- Registry record last updated 2025-12-31; status last verified 2025-12.
- Results first posted 2025-12-31.
- 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 describes a phase II, single-group study of pembrolizumab and vactosertib around surgery for colorectal cancer with resectable hepatic metastases. Enrollment is recorded as 6, and the study status is terminated. The listed interventions include pembrolizumab, vactosertib, and hepatectomy.
The primary endpoint was the proportion of patients with at least a 2-fold increase in tumor-infiltrating immune cells per unit area in post- versus pre-pembrolizumab specimens, measured by immunohistochemistry. Its timeframe is listed as up to 2 years. The record states that sponsor funding ended before the specified endpoint analyses could be completed and reports no current plans to fund them.
Posted safety summaries include 1 participant with a serious adverse event among 6 at risk, 6 with other adverse events among 6 at risk, and 0 deaths. Colitis is listed among serious adverse-event terms at 16.7%. The record does not report a control-group comparison or results for the primary endpoint.