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 A Dose Escalation Study of MLN7243 (TAK-243) in Adult Participants With Advanced Solid Tumors (NCT02045095), a non-randomized phase 1 study. The primary outcome is Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02045095 |
| Phase | Phase 1 |
| Condition | Advanced Malignant Solid Tumors |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Millennium Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with advanced solid tumors were eligible for study participation. The registry lists advanced malignant solid tumors as the condition and reports an enrollment of 29. The safety population included participants who received at least one dose of TAK-243; the number who received a dose in each cohort is described in the adverse-event results.
Intervention
The study evaluated intravenous TAK-243, an inhibitor of ubiquitin-activating enzyme. Schedule A included dose cohorts at 1 mg, 2 mg, 4 mg, 8 mg, 12 mg, and 18 mg, as well as a homozygous mutant 4 mg cohort. The recorded schedule was dosing on Days 1, 4, 8, and 11, followed by rest in a 21-day cycle.
Comparator
There was no randomized control group. The registry classifies allocation as non-randomized and the design as single-group. Dose cohorts can be described separately, but they are not like-for-like control groups: cohort assignment was not randomized, and the registry does not report a controlled comparison between doses.
Primary question
The study’s stated purpose was to evaluate safety and tolerability, establish a maximum tolerated dose, inform a recommended phase 2 dose, and identify dose-limiting toxicities. The primary outcome recorded the number of participants with one or more treatment-emergent adverse events and serious adverse events, from baseline through 30 days after the last dose of study drug.
3. Trial Design
This was a phase 1, open-label, multicenter, non-randomized study of TAK-243 in adults with advanced solid tumors. The registry lists a single-group model, while also describing separate dose cohorts. It reports no masking and no randomized comparator. Enrollment was 29. The study started on 2014-01-31, and the primary completion date was 2016-11-09. Its status is terminated; the reason for termination is not reported in the registry record.
The intervention was intravenous TAK-243, administered in Schedule A at dose levels of 1 mg, 2 mg, 4 mg, 8 mg, 12 mg, and 18 mg, with an additional homozygous mutant 4 mg cohort. The recorded schedule was infusion on Days 1, 4, 8, and 11, followed by 10 days of rest in a 21-day treatment cycle. Treatment could continue for a maximum of 12 months or until a listed discontinuation condition, such as symptomatic deterioration or disease progression. The description for the 1 mg cohort is truncated in the registry record, so its complete discontinuation wording is not reported there.
The stated aim was to assess safety and tolerability, establish the maximum tolerated dose, inform a recommended phase 2 dose, and identify dose-limiting toxicities. The registry records 19 outcome measures, including pharmacokinetic measures such as plasma concentration and measures of drug exposure, clearance, distribution, and urinary excretion. No detailed dose-escalation rules, cohort assignment procedure, or protocol for selecting a recommended dose is reported in the registry record. The listed dose cohorts therefore describe the intervention groups, but do not by themselves establish how decisions about escalation were made.
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.
Before assignment: Participants with diagnosis of advanced malignant solid tumors were enrolled in Schedule A of dose escalation phase to receive TAK-243 (MLN7243). The study was terminated prior to start of Schedule B of dose escalation phase and planned expansion because of realignment of the sponsor's pipeline program.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | Schedule A: TAK-243 1 mg | Schedule A: TAK-243 2 mg | Schedule A: TAK-243 4 mg | Schedule A: TAK-243 8 mg | Schedule A: TAK-243 12 mg | Schedule A: TAK-243 18 mg |
|---|---|---|---|---|---|---|
| STARTED | 3 | 4 | 4 | 4 | 5 | 8 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 4 | 4 | 4 | 5 | 8 |
Reasons for not completing this period:
| Reason | Schedule A: TAK-243 1 mg | Schedule A: TAK-243 2 mg | Schedule A: TAK-243 4 mg | Schedule A: TAK-243 8 mg | Schedule A: TAK-243 12 mg | Schedule A: TAK-243 18 mg |
|---|---|---|---|---|---|---|
| Other | 0 | 0 | 1 | 0 | 0 | 2 |
| Progressive Disease | 3 | 3 | 2 | 4 | 2 | 4 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 0 |
| Adverse Event | 0 | 1 | 1 | 0 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: The safety population included all participants who received at least 1 dose of TAK-243.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: The safety population included all participants who received at least 1 dose of TAK-243.
| Characteristic | Unit | Schedule A: TAK-243 Total |
|---|---|---|
| Participants analysed | 29 | |
| Age, Continuous | years | 56.8 (SD 9.27) |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 22 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 5 |
| 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 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 |
| Race (NIH/OMB): White | Participants | 22 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | Participants | 29 |
| Height | centimeter (cm) | 170.88 (SD 12.101) |
| Weight | kilogram (kg) | 79.69 (SD 16.829) |
| Body Surface Area | square meter (m^2) | 1.936 (SD 0.2364) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over Baseline up to 30 days after last dose of study drug (Cycle 10 Day 41).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome counts participants who reported one or more treatment-emergent adverse events and serious adverse events. The registry specifies the safety population as all participants who received at least one dose of TAK-243. The observation window runs from baseline through 30 days after the last dose of study drug, with the timeframe also identified as Cycle 10 Day 41.
Counting participants with an event is a binary-outcome approach: each participant is classified according to whether they experienced at least one event of the specified kind during the observation period. It is a way to describe how many participants had an event, not how many separate episodes occurred. If one participant experiences multiple events, a participant-level count does not represent those events as multiple participants.
Safety and tolerability outcomes are used in early-phase studies to describe adverse events observed during exposure and to support evaluation of dose levels. Seriousness and treatment-emergent timing are distinct concepts: the outcome includes serious adverse events and other treatment-emergent adverse events, while the registry does not establish from these counts whether an event was caused by study drug. The reported figures should therefore be read as event reporting in the defined safety population and timeframe, not as proof of causation or as a direct measure of treatment benefit. The registry does not report a separate numerical result for maximum tolerated dose, recommended phase 2 dose, or dose-limiting toxicities in the registry record for this analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The adverse-event results are descriptive counts within each dose cohort. In the 1 mg cohort, 1 of 3 participants had a serious adverse event and 3 of 3 had another treatment-emergent adverse event. At 2 mg, the corresponding counts were 1 of 4 and 4 of 4. At 4 mg, they were 2 of 4 and 4 of 4; at 8 mg, 2 of 4 and 4 of 4. At 12 mg, 1 of 5 participants had a serious adverse event and 3 of 5 had another treatment-emergent adverse event. At 18 mg, the counts were 4 of 8 and 8 of 8. In the homozygous mutant 4 mg cohort, 0 of 1 had a serious adverse event and 1 of 1 had another treatment-emergent adverse event.
These are small cohort counts, and each describes only the participants recorded in that particular cohort. A count such as 1 of 3 is not a precise estimate of the frequency that would be expected in a broader population. With few participants, a change in the experience of one person can substantially change the apparent pattern. The results should not be treated as a ranked comparison of dose safety: allocation was non-randomized, there was no control group, and the cohorts may not be comparable. The registry does not report an adjusted comparison, uncertainty interval, or inferential test for differences between dose levels.
The registry also lists serious-event terms and percentages: Escherichia bacteraemia, 33.3%; pneumonia, 25.0%; abdominal pain, 25.0%; breathing abnormalities, 25.0%; dyspnoea, 25.0%; and respiratory failure, 25.0%. These are reported as top serious terms. The registry record does not specify in the registry record the denominator used for those percentages, nor whether each participant could contribute more than one term. They should not be interpreted as cohort-specific risks or as evidence of causation.
No deaths count is reported for the listed cohorts. That is different from a statement that no deaths occurred: the death information is not reported in the registry record. Similarly, the registry information summarized for this analysis does not include numerical efficacy results, an estimate of the maximum tolerated dose, a recommended phase 2 dose, or a dose-limiting toxicity result. The available statistics support a descriptive reading of adverse-event reporting, not a conclusion about efficacy or a causal effect of TAK-243.
9. Statistical Methods Explained
The primary outcome is a participant-level binary measure. A participant either had at least one event in the defined category during the observation window or did not. This differs from an event count, which could count repeated episodes in the same person. The reported cohort figures pair the number of participants affected with the number at risk, allowing the reader to see the observed counts within each dose group without treating the groups as randomized comparisons.
What does a cohort count tell us?
A count is a direct description of what was recorded among the participants in that cohort. It does not, by itself, quantify how uncertain the corresponding population frequency is. Confidence intervals are one general statistical tool for expressing uncertainty around an estimate: they describe a range of values compatible with the data and the method used. No confidence intervals are reported for these cohort results in the registry record. With small groups, descriptive counts are especially important to read alongside the group size, because the observations are limited and a single participant’s experience can have a visible influence on the pattern.
Serious adverse events and other treatment-emergent adverse events are reported as separate categories in the cohort results. Those categories should not be presumed to be mutually exclusive, because the registry information does not state that a participant with a serious event could not also be counted among participants with another treatment-emergent event. Nor should the participant counts be read as the total number of episodes. The primary outcome description concerns participants reporting one or more events.
Why is a between-dose comparison limited?
In a randomized comparison, assignment is designed to make treatment groups comparable in expectation. This study is recorded as non-randomized and has no control group. Participants in different dose cohorts therefore cannot automatically be treated as if dose were the only meaningful difference between groups. Differences in observed counts may reflect the composition and experience of the small cohorts as well as dose; the registry does not provide information that would allow those influences to be separated. The cohort results are useful as descriptive safety information, but not as a controlled estimate of a dose effect.
Over-dispersion is a general statistical issue that can arise when variation in event counts is greater than a chosen model assumes. It matters because a model that understates variation may give overly narrow uncertainty estimates. The results described for this study are participant counts, and no model for count variation or adjustment for over-dispersion is reported in the registry record. No statistical comparison or inferential analysis is listed; the record reports zero analyses.
What is known about the analysis plan?
The registry identifies the safety population as all participants who received at least one dose of TAK-243 and gives the primary outcome timeframe as baseline through 30 days after the last dose, identified as Cycle 10 Day 41. These details define who contributes to the safety outcome and the period covered. Other analysis-population rules, including how participants with incomplete follow-up were handled, are not reported in the registry record. The registry also does not report a statistical analysis plan, a method for handling missing outcome information, or a planned inferential test.
The record lists 19 outcome measures, including pharmacokinetic outcomes such as concentration at the end of infusion, measures of area under the concentration-time curve, clearance, volume of distribution, and urinary excretion. Listing outcomes does not supply their numerical results or analysis methods. Those details are not reported in the registry record for the information.
How should sample-size illustrations be read?
The sample-size material is a planning illustration, not the trial’s original design justification and not observed power. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For outcomes other than time-to-event, the illustrations are expressed as participants per arm; time-to-event illustrations use a total event count with the Schoenfeld method. Such illustrations show how assumptions can inform future planning. They do not establish that this non-randomized dose-escalation study was designed with those assumptions, and they cannot establish the power of the completed study. The registry does not report the study’s own sample-size justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 19 outcome measures, including the primary safety outcome and secondary pharmacokinetic measures. When a study evaluates multiple outcomes, the chance of observing an apparently notable result by chance can increase if many statistical tests are conducted. A multiplicity strategy is a general statistical approach for addressing that issue, for example by specifying which outcome is primary or adjusting interpretation across multiple tests. The registry record does not report a multiplicity plan, and no statistical analyses are listed.
The safety population is defined as participants who received at least one dose of TAK-243. The primary outcome timeframe extends from baseline to 30 days after the last dose. These specifications identify the population and observation period for the stated safety measure, but do not describe how missing observations, incomplete follow-up, or withdrawals were handled. Missing-data methods and rules for participants who lacked complete outcome information are not reported in the registry record.
The registry does not report an intention-to-treat population or another analysis population for efficacy comparisons. The listed primary population is a safety population based on exposure to at least one dose. No statistical analysis plan, prespecified hypothesis test, adjustment for covariates, or method for comparing dose cohorts is reported. Because the study is non-randomized and has no control group, the separate cohort counts are descriptive; the record does not provide a basis for a confirmatory comparison of doses.
The planning illustrations use specified assumptions, but they are not the study’s original sample-size justification. The registry record does not report the rationale for the enrollment target or how the actual enrollment was determined. The absence of a reported method should not be read as evidence that a particular method was or was not used outside 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 |
|---|---|---|---|
| Schedule A: TAK-243 1 mg | 1 | 3 | 33.3% |
| Schedule A: TAK-243 2 mg | 1 | 4 | 25.0% |
| Schedule A: TAK-243 4 mg | 2 | 4 | 50.0% |
| Schedule A: TAK-243 8 mg | 2 | 4 | 50.0% |
| Schedule A: TAK-243 12 mg | 1 | 5 | 20.0% |
| Schedule A: TAK-243 18 mg | 4 | 8 | 50.0% |
| Schedule A: TAK-243 Homozygous Mutant 4 mg | 0 | 1 | 0.0% |
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 |
|---|---|
| Schedule A: TAK-243 1 mg | 3 of 3 |
| Schedule A: TAK-243 2 mg | 4 of 4 |
| Schedule A: TAK-243 4 mg | 4 of 4 |
| Schedule A: TAK-243 8 mg | 4 of 4 |
| Schedule A: TAK-243 12 mg | 3 of 5 |
| Schedule A: TAK-243 18 mg | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Schedule A: TAK-243 1 mg | Schedule A: TAK-243 2 mg | Schedule A: TAK-243 4 mg | Schedule A: TAK-243 8 mg | Schedule A: TAK-243 12 mg | Schedule A: TAK-243 18 mg |
|---|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 3 | 0 of 4 | 0 of 4 | 1 of 4 | 1 of 5 | 0 of 8 |
| Breathing abnormalities | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 2 of 8 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 2 of 8 |
| Escherichia bacteraemia | Infections and infestations | 1 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 0 of 8 |
| Viraemia and fungaemia not elsewhere classified (NEC) | Infections and infestations | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
| Sepsis | Infections and infestations | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
| Duodenal and small intestinal stenosis and obstruction | Gastrointestinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
| Small intestinal obstruction | Gastrointestinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
| Flatulence, bloating and distension | Gastrointestinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
| Abdominal distension | Gastrointestinal disorders | 0 of 3 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Schedule A: TAK-243 1 mg | Schedule A: TAK-243 2 mg | Schedule A: TAK-243 4 mg | Schedule A: TAK-243 8 mg | Schedule A: TAK-243 12 mg | Schedule A: TAK-243 18 mg |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 3 | 3 of 4 | 1 of 4 | 0 of 4 | 0 of 5 | 3 of 8 |
| Anaemia | Blood and lymphatic system disorders | 0 of 3 | 1 of 4 | 1 of 4 | 1 of 4 | 0 of 5 | 4 of 8 |
| Vomiting | Gastrointestinal disorders | 0 of 3 | 2 of 4 | 0 of 4 | 0 of 4 | 1 of 5 | 4 of 8 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 3 | 2 of 4 | 2 of 4 | 1 of 4 | 0 of 5 | 2 of 8 |
| Fatigue | General disorders | 1 of 3 | 0 of 4 | 1 of 4 | 1 of 4 | 2 of 5 | 1 of 8 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 3 | 1 of 4 | 0 of 4 | 2 of 4 | 0 of 5 | 1 of 8 |
| Headache | Nervous system disorders | 1 of 3 | 1 of 4 | 1 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
| Diarrhoea | Gastrointestinal disorders | 0 of 3 | 1 of 4 | 0 of 4 | 1 of 4 | 0 of 5 | 1 of 8 |
| Constipation | Gastrointestinal disorders | 0 of 3 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 5 | 2 of 8 |
| Asthenia | General disorders | 1 of 3 | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 5 | 1 of 8 |
Serious events with the highest arm-level rate: escherichia bacteraemia (33.3%), pneumonia (25.0%), abdominal pain (25.0%), breathing abnormalities (25.0%), dyspnoea (25.0%).
The serious adverse event figures report the number of participants affected and the number at risk in each cohort. The counts are 1 of 3 at 1 mg, 1 of 4 at 2 mg, 2 of 4 at 4 mg, 2 of 4 at 8 mg, 1 of 5 at 12 mg, 4 of 8 at 18 mg, and 0 of 1 in the homozygous mutant 4 mg cohort. The other treatment-emergent adverse-event counts are 3 of 3, 4 of 4, 4 of 4, 4 of 4, 3 of 5, 8 of 8, and 1 of 1, respectively.
These figures describe participants, not the total number or duration of individual events. They also do not establish that TAK-243 caused an event. The registry’s listing of serious-event terms includes Escherichia bacteraemia at 33.3%, and pneumonia, abdominal pain, breathing abnormalities, dyspnoea, and respiratory failure at 25.0% each. The denominator and event-counting details for these term percentages are not reported in the registry record, so they should not be read as risks for particular dose cohorts.
The death values are not reported in the registry record. This does not establish that no deaths occurred. The small cohort sizes also make the raw counts imprecise descriptions of any broader population frequency. They are most appropriately read as reported safety observations within the study’s safety population and stated timeframe.
12. What the Result Does, and Does Not, Mean
The results provide a record of adverse-event reporting among participants who received at least one dose of TAK-243. They show the number of participants with serious and other treatment-emergent adverse events within each dose cohort over the registry’s stated observation period. This is relevant descriptive information for a phase 1 study whose stated purpose was safety and tolerability, including evaluation of dose-limiting toxicities and informing dose selection.
The results do not establish that TAK-243 caused any reported event. Treatment-emergent means that an event was observed after treatment began within the defined reporting framework; it does not, on its own, determine causality. The registry does not provide a randomized control group or an adjusted analysis that could separate events associated with treatment from events that may occur in the study population for other reasons.
The cohort counts also do not establish that one dose is safer or less safe than another. Dose assignment was non-randomized, and the groups were small. No formal dose comparison or uncertainty estimates are reported. The observed counts can describe what happened among the participants recorded in each cohort, but cannot by themselves predict the experience of a larger population.
The registry record considered for these results does not report a numerical maximum tolerated dose, a recommended phase 2 dose, or a specific dose-limiting toxicity finding. It also does not report numerical efficacy outcomes. The safety counts therefore should not be interpreted as evidence that the intervention does or does not provide clinical benefit. They describe adverse-event reporting, with the limits imposed by the study design and the information recorded in the registry.
13. Why This Trial Matters Statistically
This study illustrates how early-phase dose-escalation results differ from the results of a randomized comparative trial. The central statistical task described by the registry is to characterize safety and tolerability across dose cohorts, with a stated interest in maximum tolerated dose, a recommended phase 2 dose, and dose-limiting toxicities. The reported participant counts supply a cohort-by-cohort description, not a controlled estimate of what would have happened under another treatment or no treatment.
The distinction matters because small, non-randomized cohorts support limited precision and limited causal interpretation. A participant count can be clinically informative as an observation, but it is not automatically a stable estimate of frequency. Differences across dose groups should not be taken as proof of a dose-response relationship: groups were not randomized, no control group is recorded, and no inferential comparison is reported.
The registry also makes visible the difference between a study’s purpose and its posted numerical outcomes. Its stated aim includes dose selection and identification of dose-limiting toxicities, but the results report participant counts for treatment-emergent and serious adverse events. No numerical dose-selection conclusion or statistical analysis is reported. Keeping those distinctions clear helps prevent descriptive safety data from being overread as a formal dose recommendation or an efficacy finding.
Finally, the study demonstrates why analysis populations, observation windows, and missing-data rules matter when interpreting safety outcomes. The registry defines a safety population and a follow-up window, but does not report how incomplete observations were handled. Understanding both what is recorded and what is not reported is essential for an appropriately cautious reading of early-phase evidence.
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 registry reports small dose cohorts, with between 1 and 8 participants recorded at risk in the listed groups. Such group sizes mean that the counts are limited descriptions of the participants enrolled and provide little basis for precise estimates of event frequency. No confidence intervals are reported, so the precision of cohort-level estimates is not quantified in the registry record.
Allocation was non-randomized, there was no masking, and no randomized comparator is listed. Cohort differences therefore should not be interpreted as treatment effects or as a clean comparison of dose levels. The registry does not report details of cohort assignment, escalation rules, or the decision process used to select a dose. Although the stated study purpose includes maximum tolerated dose, recommended phase 2 dose, and dose-limiting toxicities, numerical results for those aims are not reported in the information.
The registry defines the safety population and primary outcome timeframe, but does not report missing-data procedures, event-attribution methods, or details for the denominator behind the listed serious-event term percentages. The death information is not reported in the registry record. The study status is terminated, but the reason is not reported. The record also does not provide numerical efficacy results or an analysis comparing dose groups. These omissions limit interpretation and should not be filled by assumptions about the protocol or study conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Dose Escalation Study of MLN7243 (TAK-243) in Adult Participants With Advanced Solid Tumors — NCT02045095.
- Registry record last updated 2019-03-14; status last verified 2018-11.
- Results first posted 2019-03-14.
- 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
NCT02045095 is a phase 1, open-label, multicenter, non-randomized dose-escalation study of TAK-243 in adults with advanced solid tumors. The registry reports enrollment of 29 and lists dose cohorts from 1 mg through 18 mg, plus a homozygous mutant 4 mg cohort. The intervention was intravenous, on Days 1, 4, 8, and 11 of a 21-day cycle. The study status is terminated.
The stated purpose was to assess safety and tolerability, establish a maximum tolerated dose, inform a recommended phase 2 dose, and identify dose-limiting toxicities. The primary outcome counted participants with one or more treatment-emergent adverse events and serious adverse events in the safety population, from baseline through 30 days after the last dose. Cohort-specific safety counts are reported, but no statistical analyses are listed. A reason for termination, detailed missing-data methods, numerical dose-selection results, and efficacy results are not reported in the registry record.