Testing AZD1775 inC Combination With Radiotherapy and Chemotherapy in Cervical, Upper Vaginal and Uterine Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing AZD1775 inC Combination With Radiotherapy and Chemotherapy in Cervical, Upper Vaginal and Uterine Cancers (NCT03345784), a na phase 1 study. The primary outcome is Recommended Phase 2 Dose Defined as the Dose Level With < 1/6 Patients With Dose Limiting Toxicities.

2. Clinical Question

The central statistical question is therefore dose selection and tolerability in an early-phase, single-group study, rather than whether the combination improves outcomes relative to another treatment. Dose-limiting toxicity is used in this setting as a decision measure: it can help identify a dose level for later study while limiting reliance on comparisons that the design cannot support. A phase I study can describe observed safety and guide further investigation, but the record does not establish a treatment effect on cancer outcomes.

The listed secondary outcomes include toxicity frequency and severity, pharmacodynamic effects, and progression-free survival. Their analysis results are not reported in the registry record. The study status is terminated, but the reason for termination is not reported in the registry record.

3. Trial Design

This was a phase I, single-group study sponsored by the National Cancer Institute (NCI). The registry lists an enrollment of 10. Allocation is recorded as NA, masking as none, and the model as single group. These design features mean that the record does not describe random assignment or blinding, and the treatment groups should not be interpreted as randomized comparison arms.

The treatment regimen combined adavosertib with external beam radiation therapy and cisplatin. The arm descriptions distinguish dose level 1, with AZD1775 3 days per week, from dose level -1, with AZD1775 2 days per week. Both descriptions include radiation therapy and cisplatin. The regimen description specifies radiation on days 1–5; adavosertib on days 1, 3, and 5 or once daily on days 1–5; and cisplatin intravenously over 1 hour on day 1 or 3. Cycles could repeat weekly for up to 5 weeks in the absence of disease progression or unacceptable toxicity.

The registry lists the study start as 2018-05-29 and primary completion as 2022-05-10. The current status is terminated. The record does not report why the study was terminated, whether the listed enrollment is the final number enrolled, or how many participants were evaluable for the primary endpoint. The primary endpoint population is described as participants evaluable for response, but the number in that population is not reported in the registry record.

The design is suited to an early assessment of dose and toxicity, not to a definitive comparative estimate of benefit. Because the two dose levels were not randomized against each other, any observed difference between their outcomes could reflect differences in participant characteristics, treatment exposure, or chance as well as dose. The registry does not report the detailed statistical plan, eligibility criteria beyond the listed cancer types and stages, or a sample-size justification. These omissions limit the extent to which the protocol and intended inference can be reconstructed.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants that were evaluable for response.

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.

6. Primary Endpoint

The registry lists the primary outcome as Recommended Phase 2 Dose Defined as the Dose Level With < 1/6 Patients With Dose Limiting Toxicities, measured over Up to week 5.

The primary endpoint is the recommended phase II dose, defined in the registry as the dose level with < 1/6 patients experiencing dose-limiting toxicities. The timeframe is up to week 5, and the outcome is expressed as a count of participants. The stated objective is to determine the recommended phase II dose and safety profile of AZD1775 combined with radiotherapy and concurrent cisplatin in patients with gynecological cancers.

In general, a dose-limiting toxicity endpoint is used in early-phase research to support a decision about how much of an investigational treatment combination to take forward. The decision rule links a dose level to the observed frequency of toxicities that meet the study’s dose-limiting criteria. That approach is intended to balance learning about dose against the risk of unacceptable toxicity. The exact toxicity definitions, assessment procedures, and decision algorithm beyond the stated threshold are not reported in the registry record.

The endpoint does not directly measure whether cancer shrinks, whether participants live longer, or whether the combination is better than another treatment. Those are different questions. Although progression-free survival appears among the secondary outcomes, its results are not reported in the registry record. Nor does the posted information state which dose level met the primary endpoint rule. Consequently, the endpoint definition is available, but its result and the resulting recommended phase II dose cannot be determined from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what this study was designed to assess from what can be concluded from its registry entry. The interpretation below separates general methodological context from study-specific details. The record describes an early-phase dose-selection objective, but does not report a complete statistical analysis plan or endpoint results.

What does a single-group design imply?

In general, a single-group study observes outcomes among participants receiving the study regimen without a randomized control group. Such a design can describe which adverse events were recorded and can support dose-selection decisions when the protocol defines suitable criteria. It cannot by itself isolate the treatment’s effect from the natural course of disease, concurrent care, participant characteristics, or other influences. The record describes two dose-level groups, but allocation is listed as NA and the study model as single group. The groups are therefore not a randomized, like-for-like comparison.

Even if the observed event counts differ across dose levels, that difference is descriptive. With small groups, chance variation and differences among participants can have a substantial influence on the counts. A causal interpretation would require stronger design or assumptions than the registry entry establishes. The study should therefore be read primarily as an early-phase assessment of dose and safety, not as a comparative effectiveness trial.

How does the dose-selection endpoint work?

The primary endpoint defines the recommended phase II dose as the dose level with < 1/6 patients experiencing dose-limiting toxicities, with assessment up to week 5. In general, a decision rule of this kind uses observed toxicity to guide selection of a dose for later evaluation. It is not the same as estimating a precise long-term risk, and it does not directly answer whether a regimen improves disease outcomes.

The rule depends on how dose-limiting toxicity is defined, how participants are classified as evaluable, and how incomplete observations are handled. The registry describes the primary population as participants evaluable for response, but does not report the number evaluable or the full toxicity-evaluation procedures. It also does not report the toxicity definitions or a detailed algorithm for applying the threshold. Those details matter because different rules for evaluability, timing, or toxicity classification can affect a dose-selection decision.

What does a confidence interval communicate?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified method. It is not a guarantee that the true value lies in that particular interval, nor does it correct for design limitations, incomplete follow-up, or bias. The record does not report confidence intervals for the primary endpoint or the safety counts. Without participant-level data and specified analysis methods, a defensible interval cannot be reconstructed from the registry entry alone.

For a small study, uncertainty is especially important. A reported count tells how many participants in the recorded denominator experienced an event; it does not, by itself, establish a stable population rate. General statistical methods can quantify uncertainty, but any such estimate depends on assumptions and should not be mistaken for a result reported by the study. The registry’s safety figures are best read as descriptive observations in the listed groups.

Why do denominators and missing outcomes matter?

In general, an event count is meaningful only alongside the population at risk and the rules used to determine who was assessed. A participant who stops treatment early, misses an assessment, or lacks follow-up may not have the same opportunity for an event to be observed as a participant with complete observation. This can affect both toxicity summaries and time-to-event outcomes. The record lists the numbers at risk for the posted safety groups, but does not report details about missing observations, follow-up completeness, or handling of participants who were not evaluable.

Progression-free survival is listed as a secondary outcome. In general, time-to-event analyses account for differing follow-up times and may treat some participants as censored if the event has not been observed by the last available assessment. The registry does not report a progression-free survival analysis, event count, follow-up summary, or censoring method. No survival estimate or interpretation can therefore be drawn from the listed outcome name alone.

What can planning calculations establish?

In general, sample-size planning uses assumptions about the outcome, treatment effect or event frequency, significance level, allocation, and analysis method. A planning illustration based on an observed effect is not an observed power calculation and does not show that a study had a particular probability of detecting an effect after the fact. It also cannot substitute for the original design rationale.

The registry record does not report the trial’s sample-size justification, and no actual endpoint analyses are listed. It therefore cannot establish the assumptions used to choose enrollment or whether the study was intended to test a comparative hypothesis. The record’s enrollment entry is 10, but that entry alone does not explain the rationale or indicate the number included in any analysis. A planning calculation, where presented, should be treated as an illustration under its stated assumptions rather than as a trial result or a description of the original design.

Finally, multiplicity matters when many outcomes or comparisons are assessed. In general, evaluating several outcomes increases the chance of finding an apparently notable result by chance if the analyses are treated as confirmatory without adjustment or a prespecified hierarchy. This record lists a primary endpoint and secondary outcomes, but does not report multiplicity procedures or analysis results. No conclusion about statistical significance across the outcomes is available.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint focused on the recommended phase II dose and lists secondary outcomes involving toxicity, pharmacodynamic effects, and progression-free survival. It does not report analysis results for these outcomes, and the record lists 0 analyses. The statistical plan for managing multiple outcomes is not reported in the registry record.

In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are considered. If many tests are treated as confirmatory without a prespecified strategy, the chance of at least one apparently positive result can increase. Common strategies include designating a primary outcome, setting an order for testing, or adjusting inference for multiple comparisons. The registry entry does not say whether any such approach was planned. With no posted analyses, there are no findings from which to assess whether multiplicity affected interpretation.

Missing-data methods are also not reported. The primary endpoint population is described as participants evaluable for response, but the number evaluable and the handling of participants who were not evaluable are not stated. The record does not explain how incomplete toxicity assessments or missing follow-up for progression-free survival were treated. In general, missingness can affect an estimate when the chance that an observation is missing is related to a participant’s health, treatment, or outcome. The direction and magnitude of any such effect cannot be determined without information about the missing data and analysis method.

The registry does not report analysis populations, participant flow through the study, or a detailed statistical analysis plan. It is therefore unclear which participants would have been included in each outcome analysis or how deviations from the intended regimen were handled. These gaps prevent an assessment of whether the analyses followed prespecified procedures or whether exclusions could have changed the reported results.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: grade 3 diarrhea (25.0%), grade 3 lymphocyte count decreased (20.0%).

The serious adverse event entries report participants at risk and participants affected in each dose-level group. For radiation therapy, AZD1775 3 days per week, and cisplatin at dose level 1, the record lists 1 serious adverse event participant among 4 at risk and 4 participants with other adverse events among 4 at risk. For radiation therapy, AZD1775 2 days per week, and cisplatin at dose level -1, it lists 1 serious adverse event participant among 5 at risk and 5 participants with other adverse events among 5 at risk. Deaths are listed as 0 in both groups.

The record names Grade 3 Diarrhea at 25.0% and Grade 3 Lymphocyte Count Decreased at 20.0% among the top serious terms. These terms and percentages are not a full safety profile. The registry entry does not provide the participant-level details or enough context to determine how the percentages relate to the group denominators. They should not be converted into counts or compared across groups without that information.

In general, serious adverse events and other adverse events are distinct categories in safety reporting. Counts describe observed participants, not necessarily the number of separate event episodes. Small denominators make event-frequency estimates uncertain, and nonrandomized dose-level groups do not support a controlled safety comparison. These figures describe the posted safety entries; they do not establish comparative risk.

12. What the Result Does, and Does Not, Mean

The registry record describes a phase I study intended to assess safety and identify a recommended phase II dose for adavosertib with radiation therapy and cisplatin. It provides the endpoint rule, treatment schedules, status, and selected adverse-event counts. It does not post a primary endpoint result, a recommended phase II dose, or results for the listed secondary outcomes. The available information therefore does not show whether the dose-selection criterion was met.

The safety counts are observations from the listed groups. They can indicate that adverse events were recorded among participants at risk, but the small group sizes and absence of randomization limit comparisons between dose levels. The counts do not establish that a particular schedule causes more or fewer events, and they do not quantify risk for a broader population with precision. The serious event terms and percentages offer additional descriptive information, but do not form a complete account of toxicity.

The study’s termination status is recorded, but the reason for termination is not reported in the registry record. It would be inappropriate to infer that termination was caused by safety, lack of benefit, recruitment difficulty, or any other factor. The record also does not report the final analyzed population, missing-data handling, or the statistical methods used for outcomes.

In general, an early-phase dose-finding study answers a narrower question than a confirmatory trial. Its findings can inform whether and how a regimen proceeds to further research, but they do not by themselves demonstrate clinical benefit or establish comparative safety. Here, the registry information supports description of the study’s intended question and selected recorded safety figures. It does not support a conclusion about efficacy, an optimal dose, or the treatment’s effect relative to another option.

13. Why This Trial Matters Statistically

This study is statistically distinctive because its central aim is dose selection rather than a conventional test of superiority between treatments. A phase I dose rule uses observed toxicity to help choose a dose for later research. Understanding that aim helps prevent a common interpretive error: treating groups used to explore dose levels as if they were randomized treatment and control groups.

The record makes the design distinction consequential. It lists two schedules of AZD1775 alongside radiation therapy and cisplatin, but describes a single-group study with allocation recorded as NA. The safety counts can be read descriptively within each group, yet they cannot establish that one schedule is safer than the other. The groups were not identified as a randomized comparison, and the counts are small.

The endpoint also illustrates how a decision rule differs from a complete outcome analysis. The registry defines the recommended phase II dose using a dose-limiting toxicity threshold through week 5, but does not report whether any dose level met that rule. The endpoint definition alone is not a result. Distinguishing protocol intent from posted findings is essential when a registry entry contains detailed design information but limited outcome reporting.

Finally, the record lists secondary questions about toxicity, pharmacodynamic effects, and progression-free survival, while reporting 0 analyses. This matters statistically because outcome names do not supply estimates, uncertainty, or analysis methods. Without those elements, readers cannot evaluate precision, missingness, multiplicity, or the strength of any inference. The study’s statistical value in the registry record is therefore mainly in clarifying the intended dose-selection framework and showing the limits of what can be concluded from the posted safety data.

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 main limitation is that the registry entry does not report the primary endpoint result. It gives the definition of the recommended phase II dose, but not dose-limiting toxicity counts, the number evaluable for the endpoint, or the dose level selected. This prevents assessment of whether the stated decision rule was met.

The record lists 10 participants for enrollment, but does not report whether this is the final enrollment or how many participants contributed to each outcome. Safety denominators are listed for the two dose-level groups, but details about participant characteristics, treatment received, discontinuations, and follow-up are not reported. The registry also does not explain the reason for termination.

Design limits interpretation of the safety entries. The study is described as single group, allocation is NA, and masking is none. The two dose-level groups are not a randomized control comparison. Differences in their observed counts therefore cannot be attributed to dosing schedule alone. The small denominators further limit precision, and the record does not provide confidence intervals or participant-level data.

Important analysis details are absent: toxicity definitions, dose-limiting toxicity assessment procedures, the statistical analysis plan, missing-data handling, and analysis populations are not reported in the registry record. The secondary outcomes are named, but their results and methods are not posted. Without those details, the completeness and robustness of outcome analyses cannot be assessed.

The listed serious adverse event terms and percentages are only selected safety summaries, not a comprehensive account. The registry does not provide enough information to reconstruct their denominators or determine the full pattern of events. These limitations mean the posted information should be interpreted as a partial description of the trial, not as a complete report of its outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Testing AZD1775 inC Combination With Radiotherapy and Chemotherapy in Cervical, Upper Vaginal and Uterine Cancers — NCT03345784.
• Registry record last updated 2024-02-20; status last verified 2024-01.
• Results first posted 2023-06-06.
• 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.

18. Record Summary

NCT03345784 is a phase I, single-group study sponsored by the National Cancer Institute (NCI). It investigated adavosertib (AZD1775) with external beam radiation therapy and cisplatin for cervical, vaginal, and uterine cancers. The registry lists enrollment of 10, a start date of 2018-05-29, primary completion on 2022-05-10, and status as terminated.

The primary endpoint was the recommended phase II dose, defined as the dose level with < 1/6 patients experiencing dose-limiting toxicities up to week 5. The registry does not report the endpoint result or selected dose. It lists two dose-level safety groups and reports 0 deaths in each, along with serious and other adverse event counts. The reason for termination, detailed analysis methods, missing-data handling, and results for the secondary outcomes are not reported in the registry record.