This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
STAR-TREC is a randomized phase 2/3 trial in adenocarcinoma of the rectum. Its design evaluates whether organ-preservation approaches following radiotherapy or chemoradiotherapy can be studied against standard total mesorectal excision, with the phase II component focused on recruitment feasibility and the phase III component focused on successful organ preservation.
| Feature | STAR-TREC |
|---|---|
| ClinicalTrials.gov identifier | NCT02945566 |
| Acronym | STAR-TREC |
| Phase | 2/3 |
| Status | Active, not recruiting |
| Start date | 2017-06-14 |
| Primary completion | 2027-08 |
| Condition | Adenocarcinoma of the Rectum |
| Lead sponsor | University of Birmingham |
| Sponsor type | Other |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 380 |
2. Clinical Question
The trial addresses whether a strategy intended to preserve the rectum can be evaluated against standard total mesorectal excision in patients with adenocarcinoma of the rectum. The phase II component asks whether international recruitment is sufficient to sustain a phase III study, while the phase III component defines a successful organ-preservation outcome at 30 months from the start of (chemo)radiotherapy treatment.
Population
Patients with adenocarcinoma of the rectum enrolled into the randomized STAR-TREC study.
Organ-preservation strategies
Long course concurrent chemoradiation with capecitabine and radiotherapy, or short course radiotherapy.
Comparator
Standard total mesorectal excision surgery.
Primary questions
Can recruitment reach the prespecified feasibility targets, and what proportion of patients achieve successful organ preservation at 30 months?
3. Trial Design
STAR-TREC uses randomized allocation and a parallel design with three intervention arms. The trial is not masked. Its structure is unusual in that the phase II component is explicitly a feasibility study centered on recruitment, while the phase III component has a clinical outcome as its primary endpoint.
Standard TME surgery
- Standard total mesorectal excision surgery
- Procedure intervention
Long course chemoradiation
- Long course concurrent chemoradiation
- Capecitabine
- Radiotherapy
Short course radiotherapy
- Short course radiotherapy
- Radiation intervention
4. Trial Timeline and Status
Trial start
The registered study start date is 2017-06-14.
Recruitment feasibility assessment
Recruitment is measured at 12 and 24 months, with prespecified recruitment-rate targets and country-level accrual targets.
Organ-preservation endpoint
Successful organ preservation is assessed at 30 months from the start day of (chemo)radiotherapy treatment.
Primary completion
The registered primary completion date is 2027-08.
The registry status is ACTIVE_NOT_RECRUITING. The registered primary completion date is 2027-08, so the registry record describes a study that has not yet reached its registered primary completion date.
5. Primary Endpoints
| Endpoint | Time frame | Registry definition |
|---|---|---|
| Phase II (Feasibility study) Primary Outcome: Recruitment Rate | 24 Months | Measured at 12 and 24 months. Target recruitment rates are ≥4 and ≥6 patients randomised per month at 12 and 24 months respectively for total accrual of 120 international cases. |
| Phase III Primary Outcome: Organ Preservation | 30 Months from start day of (chemo)radiotherapy treatment. | Proportion of patients with successful organ preservation at 30 months. Defined as an in-situ rectum, including patients subject to transanal local resection, no defunctioning stoma, and an absence of active loco-regional cancer failure. |
Phase II: Recruitment Rate
The feasibility endpoint is a process outcome rather than a patient-level clinical efficacy endpoint. Recruitment is measured at both 12 and 24 months. The registry specifies targets of at least 4 patients randomized per month at 12 months and at least 6 patients randomized per month at 24 months, with total accrual of 120 international cases.
| Recruitment measure | Registry target |
|---|---|
| 12-month recruitment rate | ≥4 patients randomized per month |
| 24-month recruitment rate | ≥6 patients randomized per month |
| Total international accrual | 120 cases |
| UK minimum recruitment | 75 |
| Netherlands minimum recruitment | 75 |
| Denmark minimum recruitment | 30 |
The country-level targets are described as minimum recruitment required to sustain phase III. The registry states that if recruitment is on target in year two, consideration will be given to an early application for transition to phase III with a funding application and a formal protocol amendment.
Phase III: Organ Preservation
The primary phase III outcome is the proportion of patients with successful organ preservation at 30 months from the start day of (chemo)radiotherapy treatment. The registry specifies that this endpoint will be assessed for patients who prefer organ preservation.
The registry states that an in-situ rectum includes patients subject to transanal local resection.
The expected incidence of successful organ preservation is approximately 60%. This is a design expectation rather than an observed trial result.
6. Statistical Methodology
Recruitment-rate analysis
Recruitment rate is naturally treated as a count accumulated over a specified period of time. STAR-TREC defines its feasibility assessment around the number of patients randomized per month at two prespecified time points.
For STAR-TREC, the registry specifies decision targets of ≥4 patients randomized per month at 12 months and ≥6 patients randomized per month at 24 months.
The important statistical distinction is between describing the observed recruitment process and testing a clinical treatment effect. A recruitment-rate endpoint does not estimate a hazard ratio or treatment effect. It determines whether the trial has demonstrated sufficient recruitment performance to support continuation into the definitive phase.
Proportion-based analysis of organ preservation
The phase III primary outcome is a binary patient-level endpoint assessed at a fixed 30-month landmark. Each eligible patient can be classified according to whether the registry definition of successful organ preservation has been achieved at that time.
The principal quantity is a proportion, rather than a time-to-event hazard ratio. The registry's expected incidence is approximately 60%.
For a randomized three-arm study, comparisons of such proportions can be expressed as absolute differences in proportions, risk ratios, odds ratios, or model-based contrasts depending on the prespecified analysis plan. The registry endpoint description establishes the outcome definition but does not report a posted statistical analysis specifying which comparative estimator will be used.
Fixed-time endpoint versus time-to-event endpoint
The 30-month organ-preservation outcome is different from a conventional overall-survival or progression-free-survival endpoint. The registry specifies the outcome at a fixed landmark: 30 months from the start day of (chemo)radiotherapy treatment. This means the analysis is centered on the patient's status at that defined time point rather than on the instantaneous hazard of an event over continuous follow-up.
What the endpoint captures
Whether the patient satisfies the complete organ-preservation definition at the specified 30-month assessment.
What it does not automatically provide
A hazard ratio, median survival, or continuous time-to-event estimate. Those are different statistical quantities and require different endpoint definitions.
Three-arm randomized comparison
Randomization provides the basis for comparing outcomes across the three intervention strategies. Because there are three arms, a complete confirmatory analysis may involve an overall comparison followed by prespecified pairwise contrasts, depending on the statistical analysis plan.
The registry record identifies the randomized parallel design and the three interventions but does not report posted statistical analyses specifying the exact multiplicity strategy for multiple treatment contrasts.
7. Planned Analysis
Recruitment-rate endpoint
The phase II feasibility outcome would normally be summarized by the observed number of patients randomized per month at 12 and 24 months and compared with the prespecified thresholds of ≥4 and ≥6 patients randomized per month, respectively. The registry also specifies total international accrual of 120 cases and country-specific minimum recruitment targets.
The statistical interpretation is therefore primarily feasibility-oriented: the relevant question is whether recruitment performance reaches the prespecified operational targets required to support the planned phase III transition.
Organ-preservation endpoint
The phase III primary outcome would normally be analyzed as a binary proportion at 30 months. The analysis would begin with the number and proportion of patients satisfying the complete definition of successful organ preservation in each randomized arm.
For comparative inference, an appropriate analysis would normally estimate treatment-group differences with corresponding confidence intervals and a prespecified hypothesis-testing framework. Because this is a three-arm randomized study, the exact contrast structure and multiplicity adjustment are important parts of the statistical analysis plan.
Why the 30-month definition matters
The definition combines three clinical conditions: an in-situ rectum, no defunctioning stoma, and absence of active loco-regional cancer failure. Consequently, the endpoint is a composite success criterion at a fixed landmark. A patient who fails any one component does not meet the registry definition of successful organ preservation.
8. Statistical Methods Explained
Why does STAR-TREC have a recruitment-rate endpoint?
The phase II component is explicitly a feasibility study. Before a large definitive phase III comparison can be sustained, investigators need to know whether enough eligible patients can be randomized at the required rate. A recruitment-rate endpoint therefore evaluates the operational feasibility of the trial rather than the efficacy of one treatment strategy.
Why are recruitment rates evaluated at both 12 and 24 months?
The registry specifies different targets at the two time points: ≥4 patients randomized per month at 12 months and ≥6 patients randomized per month at 24 months. Evaluating recruitment at both points allows the feasibility assessment to consider whether recruitment is maintaining the required pace as the study progresses.
Why is organ preservation a proportion rather than a hazard ratio?
The registry defines successful organ preservation at a specific landmark: 30 months from the start day of (chemo)radiotherapy treatment. The primary quantity is therefore the proportion of patients who meet the complete success definition at that time. A hazard ratio would instead describe relative instantaneous event rates over time and would require a time-to-event endpoint.
What does a 60% expected incidence mean?
The registry's approximately 60% figure is the expected incidence of successful organ preservation. It is a planning assumption or expectation. It does not establish that 60% of participants actually achieved successful organ preservation.
Why does the three-arm design affect statistical analysis?
With three randomized arms, there are multiple possible comparisons. An overall three-group comparison and individual pairwise contrasts answer different questions. If several confirmatory comparisons are performed, the statistical plan must specify how type I error is controlled across those comparisons.
Why is the complete endpoint definition important?
The endpoint is not simply preservation of the rectum. Successful organ preservation requires an in-situ rectum, no defunctioning stoma, and absence of active loco-regional cancer failure at the specified time point. The composite definition therefore determines exactly which patients are counted as successes.
9. Non-Inferiority, Superiority, and Hypothesis Structure
The registry description does not provide a posted non-inferiority margin or a posted hypothesis-testing framework for the phase III organ-preservation endpoint. The primary endpoint is instead described as the proportion of patients with successful organ preservation at 30 months.
This distinction matters because the statistical interpretation of a trial depends on the prespecified hypothesis. A superiority analysis asks whether one strategy produces a sufficiently different outcome from another. A non-inferiority analysis asks whether the experimental strategy is not worse than the comparator by more than a prespecified clinically acceptable margin. The ClinicalTrials.gov record does not identify such a margin.
Known from the registry
The phase III endpoint is successful organ preservation at 30 months, expressed as a proportion.
Not specified in the registry data
No non-inferiority margin, posted p-value, confidence interval, or formal hypothesis-test result is reported.
10. Interim Analysis, Multiplicity, and Missing Data
Interim analysis
The registry describes a phase II feasibility decision process based on recruitment performance at 12 and 24 months. It states that if recruitment is on target in year two, consideration will be given to an early application for transition to phase III with a funding application and a formal protocol amendment.
This is an operational transition decision based on recruitment feasibility. The registry data does not report an interim efficacy analysis of the phase III organ-preservation endpoint or an alpha-spending procedure.
Multiplicity
The randomized design has three arms, creating multiple possible comparisons. However, the registry information does not report a formal multiplicity adjustment or a prespecified hierarchy for those comparisons. Such details would ordinarily be specified in the statistical analysis plan when multiple confirmatory comparisons are planned.
Missing data and imputation
The registry endpoint definition identifies the 30-month assessment but does not report a missing-data or imputation method. For a fixed-time binary endpoint, the treatment of patients without an evaluable 30-month status can materially affect the estimated proportion, so the prespecified analysis population and missing-data rules are important components of the final statistical analysis.
11. Stratification and Analysis Populations
The registry identifies randomized allocation and a parallel three-arm design, but the ClinicalTrials.gov record does not specify stratification factors or detailed analysis-population definitions.
| Analysis feature | Registry information |
|---|---|
| Randomization | Yes |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Number of arms | 3 |
| Detailed stratification factors | Not reported in the registry information provided |
| Detailed efficacy analysis population | Not reported in the registry information provided |
| Detailed missing-data strategy | Not reported in the registry information provided |
Randomization remains the key design feature supporting causal comparison. The lack of masking is also an important design characteristic: the registry identifies the trial as unmasked, meaning the intervention assignment is not blinded.
12. Safety and Adverse Events
The registry information provided identifies the trial's three interventions but does not report serious adverse-event counts or other posted safety results by randomized arm.
| Safety feature | Registry information |
|---|---|
| Serious adverse events by arm | Not reported |
| Arm-specific adverse-event estimates | Not reported |
| Posted statistical safety analysis | None |
Safety would ordinarily be summarized separately from the primary organ-preservation endpoint. Because the three arms involve materially different intervention types—standard TME surgery, long course chemoradiation, and short course radiotherapy—the denominators, exposure periods, event definitions, and severity categories would all matter in a complete safety analysis.
13. Why This Trial Matters Statistically
STAR-TREC is a useful statistical teaching case because its design connects feasibility assessment with a subsequent randomized clinical endpoint. The phase II component asks whether recruitment is sufficient to sustain the study, while the phase III component moves to a patient-level outcome defined at a fixed 30-month landmark.
| Statistical concept | How it appears in STAR-TREC |
|---|---|
| Randomization | Patients are assigned through a randomized three-arm design. |
| Parallel-group design | The three interventions are evaluated in parallel. |
| Feasibility analysis | Phase II uses recruitment rate as the primary outcome. |
| Recruitment rate | Targets are ≥4 and ≥6 patients randomized per month at 12 and 24 months. |
| Fixed-time binary endpoint | Phase III measures successful organ preservation at 30 months. |
| Composite endpoint definition | Organ preservation requires all specified clinical conditions to be satisfied. |
| Three-arm comparisons | Multiple possible treatment contrasts must be distinguished statistically. |
| Expected incidence | The registry gives an expected successful-organ-preservation incidence of approximately 60%. |
| Missing-data considerations | Thirty-month status must be defined and handled consistently in the final analysis. |
| Unmasked design | The registry identifies masking as none. |
14. Interpreting a Future Organ-Preservation Estimate
If a future analysis reports a successful organ-preservation proportion, that estimate should first be read as the percentage of evaluable patients meeting the complete 30-month definition. It should not be interpreted as a treatment effect until it is compared with the corresponding randomized group or groups.
An absolute difference between two randomized proportions would describe the difference in the probability of successful organ preservation between those groups at the specified 30-month landmark. Unlike a relative measure, it directly describes the separation in percentage points.
A confidence interval around a proportion or treatment contrast would quantify statistical uncertainty associated with the estimated effect under the chosen model and sampling framework. It would not describe the range of outcomes expected for every individual patient.
A p-value would address compatibility of the observed data with a specified null hypothesis under the prespecified statistical model. It would not measure the size or clinical importance of the organ-preservation effect.
15. Important Limitations and Interpretation Issues
- No posted results: the registry contains the study design and registered primary endpoints but no posted statistical analyses or numerical outcome results.
- Feasibility versus efficacy: recruitment rate and successful organ preservation are fundamentally different endpoint types and should not be analyzed or interpreted in the same way.
- Fixed-time endpoint: the phase III endpoint is defined at 30 months from the start day of (chemo)radiotherapy treatment, so the timing of assessment is part of the endpoint itself.
- Composite success criterion: successful organ preservation requires an in-situ rectum, no defunctioning stoma, and absence of active loco-regional cancer failure.
- Three-arm multiplicity: multiple potential treatment comparisons create a need for a prespecified contrast and multiplicity strategy if more than one comparison is confirmatory.
- Missing outcomes: the registry information provided does not specify how patients without an evaluable 30-month status will be handled statistically.
- Expected versus observed incidence: the approximately 60% expected incidence is a planning expectation, not an observed result.
- Unmasked design: the registry identifies masking as none, which is relevant when considering outcomes that can involve clinical assessment or treatment decisions.
- Recruitment targets: country-level recruitment targets are operational criteria and should not be confused with treatment efficacy endpoints.
16. Clinical Interpretation vs Statistical Interpretation
Statistical interpretation
The registered design creates a randomized three-arm comparison, with phase II recruitment feasibility followed by a phase III fixed-time organ-preservation endpoint. The registry does not contain posted estimates, confidence intervals, or p-values.
Clinical interpretation
The phase III outcome is clinically structured around preservation of the rectum without a defunctioning stoma and without active loco-regional cancer failure at 30 months. The registry's expected incidence is approximately 60%.
17. What the Registry Establishes About the Study
The ClinicalTrials.gov record establishes several important features of the trial design. STAR-TREC is randomized, uses three parallel arms, is unmasked, and has a primary purpose of treatment. Its registered status is active, not recruiting, with a start date of 2017-06-14 and a primary completion date of 2027-08.
| Domain | Registered information |
|---|---|
| Condition | Adenocarcinoma of the Rectum |
| Intervention 1 | Standard TME surgery |
| Intervention 2 | Long course concurrent chemoradiation with capecitabine and radiotherapy |
| Intervention 3 | Short course radiotherapy |
| Phase II primary outcome | Recruitment Rate |
| Phase III primary outcome | Organ Preservation |
| Phase II time frame | 24 Months |
| Phase III time frame | 30 Months from start day of (chemo)radiotherapy treatment. |
| Expected organ-preservation incidence | Approximately 60% |
18. Statistical Concepts in This Trial
STAR-TREC illustrates a different statistical pattern from a conventional two-arm time-to-event oncology trial. The key concepts are feasibility thresholds, randomized multi-arm comparison, fixed-time binary outcomes, composite endpoint construction, and interpretation of proportions.
19. Sources
- ClinicalTrials.gov: NCT02945566 — STAR-TREC.
- PubMed: PubMed record.
- PubMed: PubMed record.
- PubMed: PubMed record.
- PubMed: PubMed record.
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20. Record Summary
STAR-TREC provides a useful example of how clinical-trial statistics can change across development stages. The phase II component uses recruitment rate as a feasibility endpoint, with explicit monthly recruitment targets at 12 and 24 months and country-level accrual targets. The phase III component uses successful organ preservation at 30 months as its primary outcome, with a definition requiring an in-situ rectum, no defunctioning stoma, and absence of active loco-regional cancer failure. The randomized, three-arm, parallel design provides the framework for comparative analysis, while the absence of posted statistical analyses means that the registry currently supplies the endpoint definitions and design rather than observed treatment-effect estimates.