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 TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer (NCT04166435), a na phase 2 study. The primary outcome is Overall Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04166435 |
| Phase | Phase 2 |
| Condition | Colorectal Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced colorectal cancer whose tumors had MGMT promoter hypermethylation. The registry lists colorectal cancer as the condition and describes the study population as subjects with MGMT promoter hypermethylated advanced colorectal cancer. The enrollment recorded for the study is 11, but that figure alone does not establish how many participants contributed to each endpoint.
Intervention
The combination of temozolomide and olaparib. The listed regimen was temozolomide 75 mg/m2 orally on days 1-7 every 3 weeks, together with olaparib 150 mg orally twice daily on days 1-21 in a 21-day cycle.
Comparator
There was no separate comparison group. The registry describes a non-randomized, single-group study with allocation recorded as NA and no masking. Consequently, the study does not directly compare the combination with another treatment or with a control group.
Primary question
The primary endpoint was overall response rate, assessed using RECIST before and after treatment, with a timeframe of up to 1.5 years. The registry describes response categories and defines clinical benefit as CR, PR, or SD after treatment from the start of treatment. It does not report a numerical response result, so the primary question cannot be answered from the posted results alone.
3. Trial Design
This was a Phase II, non-randomized, open-label, single-group study sponsored by Yale University. The registry lists the study as completed, with enrollment of 11. Its recorded start date is 2020-06-17 and its primary completion date is 2022-01-06. Allocation is recorded as NA, and masking as none. These design features mean that participants received the listed combination without a randomized control group and without masking.
The intervention was temozolomide plus olaparib. The registry describes temozolomide at 75 mg/m2 orally on days 1-7 every 3 weeks and olaparib at 150 mg orally twice daily on days 1-21, in a 21-day cycle. The study population was described as patients with MGMT promoter hypermethylated advanced colorectal cancer.
The primary outcome was overall response rate, with assessment by RECIST before and after treatment and a timeframe of up to 1.5 years. Secondary outcomes listed in the registry were the count of participants with adverse events greater or equal to 3, progression-free survival, and overall survival. The record lists 4 outcome measures but 0 analyses. It does not report the full details of the protocol, eligibility criteria, treatment exposure, or methods used to analyze the outcomes.
With a single group, the design can describe outcomes among participants who received the combination, if outcome results are reported. It cannot provide a randomized estimate of how outcomes would differ under another treatment or under no treatment. Any interpretation of outcome counts also depends on knowing which participants were assessed and how missing observations were handled; those details are not reported in the registry record.
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 | Temozolomide + Olaparib |
|---|---|
| STARTED | 11 |
| COMPLETED | 9 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Temozolomide + Olaparib |
|---|---|
| 2 patients ineligible for response | 2 |
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 | Temozolomide + Olaparib |
|---|---|---|
| Participants analysed | 9 | |
| Age, Customized | years | 59 (45 to 78) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 4 |
| Race/Ethnicity, Customized: White | Participants | 8 |
| Race/Ethnicity, Customized: Black | Participants | 1 |
| Region of Enrollment: United States | participants | 9 |
| ECOG performance status: 0-Fully active, able to carry on all pre-disease performance without restriction | Participants | 3 |
| ECOG performance status: 1-No physically strenuous activity but ambulatory and can carry out light or sedentary activities | Participants | 6 |
| ECOG performance status: 2-Capable of selfcare but can't carry out any work activities; up to about 50% of waking hours | Participants | 0 |
| ECOG performance status: 3-Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours | Participants | 0 |
| ECOG performance status: 4-Completely disabled; cannot carry on any selfcare; totally confined to bed or chair | Participants | 0 |
| ECOG performance status: 5-Dead | Participants | 0 |
| Side of primary tumor: Left | Participants | 4 |
| Side of primary tumor: Right | Participants | 5 |
| Tumor Grade: Poorly differentiated | Participants | 3 |
| Tumor Grade: Moderately differentiated | Participants | 6 |
| Molecular Results: KRAS mutated | Participants | 7 |
| Molecular Results: KRAS/RAF wildtype | Participants | 2 |
| Number of prior therapies: 2 | Participants | 2 |
| Number of prior therapies: ≥ 3 | Participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate, measured over Up to 1.5 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is overall response rate, measured in participants and assessed using the Response Evaluation Criteria in Solid Tumors, or RECIST. The registry states that response was assessed before and after treatment. It defines complete response as disappearance of all target lesions, partial response as at least a 30% decrease in the sum of target-lesion diameters, and stable disease as neither sufficient shrinkage for partial response nor sufficient increase for progressive disease. It separately defines clinical benefit as the sum of complete response, partial response, or stable disease after treatment from the start of treatment.
Response endpoints are used to describe whether measurable disease has met prespecified categories of change during an assessment period. They can offer a standardized way to characterize tumor response in a clinical study. General explanation: a response rate is a proportion based on participants meeting a response definition, so its interpretation depends on the definition, assessment schedule, and participants included in the analysis.
The registry does not report the number of participants with complete or partial response, a numerical overall response rate, a confidence interval, or a test result. It also does not clarify in the posted results how the endpoint calculation relates to its separate definition of clinical benefit. Therefore, the endpoint's intended measurement is described, but its observed result and precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record identifies a completed Phase II study with enrollment of 11 and a primary endpoint of overall response rate. It does not include a numerical result for that endpoint. In particular, no count of participants with complete response or partial response, overall response rate, confidence interval, or statistical test is reported. The endpoint therefore cannot be interpreted as showing a particular response frequency or degree of precision.
The record lists 4 outcome measures and 0 analyses. Although it describes the primary endpoint and the RECIST response categories, a definition is not an outcome result. The stated timeframe is up to 1.5 years, but the record does not report the timing or completeness of individual assessments. It also does not report how many participants were evaluable for response or how missing response assessments were handled.
The safety information is limited to the recorded participant counts. For the temozolomide plus olaparib group, 9 participants were listed as at risk for serious adverse events and 1 as affected; 0 deaths were recorded. For other adverse events, 9 participants were listed as at risk and 9 as affected. Nausea is listed among the top serious terms at 11.1%. These figures describe the registry entries, not a comparison with another group. The record does not give event-level detail, observation time, or a comprehensive account of how events were collected.
Because the study had a single group and no randomized comparator, the results cannot establish how outcomes would differ under an alternative treatment. A single-group outcome can describe what was observed among participants, but it cannot separate treatment effects from other explanations, such as the course of the disease or differences among participants. The absent response result further prevents a quantitative interpretation of the primary endpoint.
General explanation: a confidence interval describes uncertainty around an estimate, while a statistical test evaluates data against a specified null hypothesis under stated assumptions. Neither can be interpreted without a reported estimate and analysis. No confidence interval, p-value, or analysis result for the primary endpoint is reported in the registry record. The record also does not report the trial's own sample-size justification or a statistical analysis plan, so those should not be inferred from the registry's design label or enrollment count.
9. Statistical Methods Explained
The record describes a binary primary outcome measured as participants: overall response rate. In this setting, the underlying observations would ordinarily distinguish participants who meet the response definition from those who do not. The registry names RECIST and defines complete response, partial response, and stable disease. It does not report the response counts or the analysis result, so no observed response estimate can be interpreted from the record.
What an estimate would represent
General explanation: a response-rate estimate describes the fraction of the analyzed participants who meet the specified response criterion. Its meaning depends on which categories count as a response, which participants are included in the denominator, and the assessment time. Here, the registry identifies overall response rate as the primary endpoint and lists RECIST categories, but does not report a numerical estimate or explain the analysis denominator. It also defines clinical benefit to include stable disease, a category distinct from the complete and partial response definitions. The posted results do not resolve how the endpoint calculation handled that distinction.
Why uncertainty matters
General explanation: a confidence interval expresses the range of values reasonably compatible with the observed data under the method used. Wider intervals indicate less precision, while narrower intervals indicate greater precision, subject to the method's assumptions. A point estimate without an interval can conceal substantial uncertainty, especially when the analyzed group is limited. No interval is reported for the primary endpoint, and no response count or estimate is available from which to assess its precision.
What a test result would mean
General explanation: a p-value is interpreted in relation to a specified null hypothesis, an analysis method, and the data. It is not a measure of clinical importance, and it does not by itself establish that a treatment caused an outcome. The registry lists 0 analyses and reports no p-value for the primary endpoint. The record does not state a null hypothesis or a testing procedure, so a test-based interpretation is not possible.
Design and comparison
The trial is recorded as single-group, non-randomized, and open-label, with no masking. General explanation: random allocation can help balance measured and unmeasured participant characteristics between groups, while masking can reduce some forms of knowledge-related influence on assessment. Neither feature supplies a guarantee of unbiased results, but their absence means that this study does not offer a randomized between-group comparison. A before-and-after response assessment within participants is not the same as a controlled estimate of the difference between treatments.
The allocation field is NA, consistent with the listed single-group design. There is no like-for-like control arm, so a relative treatment effect cannot be estimated from a randomized comparison in this study. The registry does not report adjustments for prognostic factors or other analysis methods that might have been used; those methods should not be assumed.
Planning calculations are not trial results
General explanation: sample-size planning asks how many participants might be needed to detect an assumed effect under chosen statistical assumptions. Such calculations are planning illustrations, not observed outcomes and not evidence that a study had a particular probability of finding an effect. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. The record explicitly distinguishes these illustrations from the trial's own design. They should not be read as the trial's original sample-size justification or as observed power. The trial itself is recorded as a single-group study, so the equal-allocation assumption in a planning illustration does not describe its design.
The record does not report the trial's own sample-size justification, assumptions used when planning enrollment, or interim analyses. Nor does it provide the primary endpoint's analysis method, confidence interval, or test result. These omissions limit what can be concluded statistically: the design and endpoint are described, but the primary outcome's magnitude and uncertainty are not.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and secondary outcomes, but does not report an analysis plan explaining how multiple outcomes or statistical tests were handled. No adjustment for multiplicity, hierarchy of testing, or strategy for interpreting results across endpoints is reported in the registry record. Without those details, it is not possible to determine whether any reported tests were intended as confirmatory or exploratory; in any case, the record lists 0 analyses.
Missing-data handling is also not reported. The enrollment count is 11, while the serious and other adverse-event counts use 9 participants at risk. Those figures should not be assumed to describe the same analysis population as the primary endpoint. The registry does not explain why the safety denominators differ from enrollment, whether participants lacked follow-up, or how the response endpoint treated participants without an assessment.
The record does not identify a primary analysis population, such as all enrolled participants or only those evaluable for response. It also does not report the number assessed for the primary outcome, exclusions from any analysis, or sensitivity analyses for missing observations. General explanation: missing observations can affect both an estimated outcome and its precision, and different handling choices can lead to different interpretations. Without the analysis population and missing-data methods, the primary endpoint cannot be reconstructed from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Temozolomide + Olaparib | 1 | 9 | 11.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Temozolomide + Olaparib | 0 of 9 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Temozolomide + Olaparib | 9 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Temozolomide + Olaparib |
|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temozolomide + Olaparib |
|---|---|---|
| White blood cell decreased | Investigations | 6 of 9 |
| Neutrophil count decreased | Investigations | 5 of 9 |
| Platelet count decreased | Investigations | 5 of 9 |
| Anemia | Blood and lymphatic system disorders | 4 of 9 |
| Nausea | Gastrointestinal disorders | 3 of 9 |
| Lymphocyte count decreased | Investigations | 3 of 9 |
| Fatigue | General disorders | 2 of 9 |
| Anorexia | Metabolism and nutrition disorders | 2 of 9 |
| Aspartate aminotransferase increased | Investigations | 2 of 9 |
| Constipation | Gastrointestinal disorders | 1 of 9 |
Serious events with the highest arm-level rate: nausea (11.1%).
The registry records 9 participants at risk for serious adverse events and 1 participant affected in the temozolomide plus olaparib group. It records 0 deaths. For other adverse events, 9 participants are listed as at risk and 9 as affected. Nausea is listed among the top serious terms at 11.1%.
These entries should be read as counts and a listed term, not as a comparison with another treatment group. There is no control group in this single-group study. The serious-event figures are distinct from the listed secondary outcome concerning participants with adverse events greater or equal to 3; the registry does not provide a result for that outcome in the posted record. Seriousness and a severity threshold are not interchangeable concepts, so the categories should not be treated as equivalent.
The record does not give event-level descriptions, timing, duration, exposure-adjusted rates, or detail about the safety analysis population. The 9 participants at risk for safety outcomes should not be assumed to represent all 11 enrolled participants or the primary endpoint population. These limitations prevent broader comparisons or conclusions about the frequency of events outside the recorded counts.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed Phase II study of temozolomide plus olaparib in people with MGMT promoter hypermethylated advanced colorectal cancer. It provides the planned primary endpoint, the RECIST response categories, the treatment regimen, and selected safety counts. It does not report the numerical overall response rate or an analysis of that endpoint. The central efficacy result therefore cannot be determined from the posted results.
The record's safety entries show that 1 of the 9 participants listed as at risk was affected by a serious adverse event, that 9 of 9 listed as at risk were affected by other adverse events, and that 0 deaths were recorded. Nausea is listed among the top serious terms at 11.1%. These are descriptive registry figures. With no comparator group, they do not establish how the counts would compare with another treatment or with a different study population.
General explanation: an outcome observed after treatment does not, by itself, show that treatment caused the outcome. A control group and a suitable comparison design can help distinguish treatment-related differences from other influences. This study's single-group, non-randomized design does not make that controlled comparison. Likewise, the absence of a reported response estimate means the primary endpoint cannot be judged for size or precision from the registry entry.
The record also does not report analysis details for the listed secondary outcomes, a statistical analysis plan, or missing-data methods. Those omissions do not establish that an analysis was never conducted; they mean that it is not reported in the registry record. The enrollment count alone cannot substitute for endpoint-specific denominators or results.
Accordingly, the record supports a description of the study's design, intervention, endpoint definitions, and posted safety entries. It does not support a quantitative conclusion about the primary response outcome or a causal comparison with another treatment. The stated completion status is a study-record status, not a substitute for reported outcome estimates.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a defined endpoint and a reported result. The registry names overall response rate as the primary outcome and describes RECIST categories, but does not include the response estimate, participant count by category, confidence interval, or test result. A detailed endpoint definition can clarify what investigators intended to measure, but it cannot show what the measured outcome was.
The single-group design also matters for interpretation. A study without random allocation to a comparator can describe outcomes among participants receiving the combination, but it cannot estimate a randomized difference between treatments. This is especially important when readers are tempted to interpret a post-treatment observation as evidence of a treatment effect. The design supports a narrower descriptive question than a controlled comparative trial.
The distinction between enrollment and endpoint populations is another statistical issue. The registry reports enrollment of 11 and safety denominators of 9 at risk, yet does not report the primary-endpoint denominator. Readers cannot assume that all enrolled participants contributed to every outcome. Clear reporting of who was analyzed and how missing assessments were treated is necessary to understand estimates and their uncertainty.
Finally, the registry lists 0 analyses and does not report methods for multiplicity, missing data, or the trial's own sample-size justification. Planning illustrations based on an observed effect are not evidence of observed power and do not replace the original design rationale. In this record, design details and outcome definitions are available, while the principal efficacy estimate and key inferential details are not. That contrast makes careful separation of reported details from unreported results essential.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. No overall response rate, response counts, confidence interval, or test result is available. Although RECIST categories are defined and the assessment timeframe is listed as up to 1.5 years, the record does not describe the timing or completeness of response assessments or the endpoint denominator.
The study is recorded as non-randomized and single-group, with no masking. It therefore lacks a control group for estimating a comparative treatment effect. The registry record does not report an adjustment strategy that could address differences in participant characteristics, and none should be assumed. Open-label assessment may also matter for outcomes involving judgment, but the record does not state how assessments were conducted beyond naming RECIST.
The enrollment count of 11 does not resolve the size of the analysis population. Safety entries list 9 participants at risk, but the record does not explain the difference or state how many participants were evaluable for response. Missing-data methods and analysis populations are not reported. These gaps limit interpretation of both the safety counts and any potential response result.
Other limitations specific to this record include the absence of reported analyses despite the listing of 4 outcome measures, and the lack of reported details on multiplicity, interim analyses, and the trial's own sample-size justification. The posted safety information includes selected counts and a top serious term, but not comprehensive event-level data or exposure duration. These are limitations of what is reported in the registry record and should not be taken as evidence that unreported analyses or information do not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: TMZ + Olaparib for MGMT Hypermethylated Colorectal Cancer — NCT04166435.
- Registry record last updated 2023-09-06; status last verified 2023-08.
- Results first posted 2023-01-30.
- 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
NCT04166435 is a completed, open-label, non-randomized Phase II single-group study sponsored by Yale University. It enrolled 11 participants and evaluated temozolomide plus olaparib in advanced colorectal cancer with MGMT promoter hypermethylation. The listed regimen was temozolomide 75 mg/m2 orally on days 1-7 every 3 weeks and olaparib 150 mg orally twice daily on days 1-21 in a 21-day cycle.
The primary endpoint was overall response rate by RECIST, with a timeframe of up to 1.5 years. The registry lists 4 outcome measures and 0 analyses, and does not report a numerical primary endpoint result. Safety entries list 9 participants at risk for serious adverse events, 1 affected, 0 deaths, and 9 at risk and 9 affected for other adverse events. Nausea is listed among the top serious terms at 11.1%. The record does not provide a randomized comparison or the analysis details needed to interpret efficacy estimates.