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 Trial of Pemetrexed and Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer (NCT00489359), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00489359 |
| Phase | Phase 1, Phase 2 |
| Condition | Ovarian Cancer, Primary Peritoneal Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 86 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned patients with recurrent ovarian or primary peritoneal cancer. Its stated purpose was to assess the combination in patients with platinum-sensitive ovarian cancer, and it also included patients with primary peritoneal cancer. The registry record reports enrollment of 86, but the population analyzed for the primary endpoint was zero because the maximum tolerated dose was not determined.
Intervention
Patients received pemetrexed with carboplatin in Phase 1 or Phase 2. Both drugs were administered intravenously on Day 1 of a 21-day cycle. Pemetrexed was infused over approximately 10 minutes; carboplatin was infused over approximately 30 minutes, beginning approximately 30 minutes after the pemetrexed infusion ended. Phase 1 explored dose combinations, while the Phase 2 regimen is identified as pemetrexed 500 with carboplatin AUC 6.
Comparator
There was no randomized control group. The trial is recorded as non-randomized, unmasked, and single-group. Phase 1 dose groups and the Phase 2 cohort represent different dose combinations or phases of the study; they should not be read as randomized, like-for-like treatment and control groups. The registry record does not report a separate comparator treatment.
Primary question
The primary Phase 1 question was the maximum tolerated dose of pemetrexed in combination with carboplatin, measured in mg/m^2. The registry description says dose escalation was to be guided by dose-limiting toxicities. It also states that the maximum tolerated dose was not determined in this study, so zero participants were analyzed for that endpoint. This primary result therefore does not provide a dose estimate.
The clinical question is about dose finding, not a randomized comparison of treatment effectiveness. The registry lists additional outcomes, including toxicity, tumor response, time to response, duration of response, and time to disease progression. Their names indicate the outcomes of interest, but outcome names alone do not establish how the combination performed. The registry record does not report a comparative estimate of efficacy, and the single-group design would not supply a randomized control contrast.
3. Trial Design
This was a completed Phase 1 and Phase 2 clinical trial of pemetrexed combined with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. The registry records the allocation as non-randomized, the masking as none, and the model as single-group. Enrollment was 86. The study start is recorded as 2005-07 and primary completion as 2010-02.
The interventions are the two drugs administered in both phases. In the Phase 1 and Phase 2 descriptions, pemetrexed was given intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin was given intravenously over approximately 30 minutes on Day 1, starting approximately 30 minutes after the pemetrexed infusion ended. The Phase 1 adverse-event groups list several dose combinations. The Phase 2 group is identified as pemetrexed 500 + carboplatin AUC 6.
Phase 1 was intended to determine a maximum tolerated dose based on the observed pattern of dose-limiting toxicity. The record describes planned increases in pemetrexed dose up to 900 mg/m^2 and carboplatin AUC up to 6 mg/mL*min. It also says that further dose escalations were not explored based on results from a different Phase 2 study. The maximum tolerated dose was not determined in this study.
Because allocation was not randomized and there was no masking, the dose groups do not create a randomized comparison. The registry record does not report a separate control arm, a statistical analysis plan, or a sample-size justification. Enrollment is the overall study figure; it should not be substituted for the endpoint-specific analyzed population, which is reported as zero for the primary endpoint.
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: Phase 1 and Phase 2 were conducted in different participants (i.e., Phase 1 participants did not also participate in Phase 2).
Overall Study
| Stage | Pemetrexed/Carboplatin Phase 1 | Pemetrexed/Carboplatin Phase 2 |
|---|---|---|
| STARTED | 20 | 66 |
| COMPLETED | 13 | 37 |
| NOT COMPLETED | 7 | 29 |
Reasons for not completing this period:
| Reason | Pemetrexed/Carboplatin Phase 1 | Pemetrexed/Carboplatin Phase 2 |
|---|---|---|
| Death | 0 | 2 |
| Progressive Disease | 5 | 6 |
| Lost to Follow-up | 1 | 0 |
| Withdrawal by Subject | 1 | 5 |
| Adverse Event | 0 | 16 |
Analysis population for the primary outcome, as defined in the registry: MTD was not determined in this study, so zero participants were analyzed.
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 | Pemetrexed/Carboplatin Phase 1 | Pemetrexed/Carboplatin Phase 2 | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 66 | 86 | |
| Age Continuous | years | 56.99 (SD 11.06) | 57.71 (SD 10.44) | 57.54 (SD 10.52) |
| Sex: Female, Male: Female | Participants | 20 | 66 | 86 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Caucasian | participants | 20 | 59 | 79 |
| Race/Ethnicity, Customized: Hispanic | participants | 0 | 7 | 7 |
| Region of Enrollment: Canada | participants | 0 | 7 | 7 |
| Region of Enrollment: Argentina | participants | 0 | 14 | 14 |
| Region of Enrollment: Poland | participants | 0 | 5 | 5 |
| Region of Enrollment: Germany | participants | 20 | 31 | 51 |
| Region of Enrollment: Sweden | participants | 0 | 9 | 9 |
| Performance Status: ECOG Status 0 | participants | 3 | 46 | 49 |
| Performance Status: ECOG Status 1 | participants | 17 | 20 | 37 |
| Tumor Type: Ovarian Cancer | participants | 15 | 61 | 76 |
| Tumor Type: Peritoneal Cancer | participants | 5 | 5 | 10 |
| Platinum-free interval: <6 months | participants | 0 | 3 | 3 |
| Platinum-free interval: 6-12 months | participants | 6 | 23 | 29 |
| Platinum-free interval: >12 months | participants | 14 | 40 | 54 |
6. Primary Endpoint
The registry lists the primary outcome as Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin, measured over First treatment to toxicity (up to 18 months).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/m^2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the Phase 1 maximum tolerated dose of pemetrexed in combination with carboplatin, expressed in mg/m^2. The registry describes dose escalation as being guided by the observed pattern of dose-limiting toxicity. It states that the intended pemetrexed doses could increase up to 900 mg/m^2 and carboplatin AUC up to 6 mg/mL*min, subject to the escalation rules and observed toxicity.
In general, a maximum tolerated dose is used in dose-finding research to identify a dose level judged acceptable under a prespecified toxicity rule. Such an endpoint helps distinguish dose selection from later questions about comparative effectiveness. It is meaningful only alongside the rule used to define toxicity, the observation period, and the participants actually assessed. Here, the record describes the toxicity-based approach and gives the timeframe as first treatment to toxicity, up to 18 months.
The registry record says that the maximum tolerated dose was not determined in this study, and that zero participants were analyzed for this endpoint. Therefore, the primary endpoint has no reported dose estimate. The fact that the record describes planned dose levels does not mean the endpoint was reached or that the highest listed dose was established as tolerable. The record also states that further dose escalations were not explored based on results from a different Phase 2 study. A completed study status does not change the reported absence of a determined maximum tolerated dose.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical finding is limited but clear: the registry record states that the Phase 1 maximum tolerated dose was not determined, and zero participants were analyzed for that primary endpoint. This is not an estimate with wide uncertainty; it is an endpoint for which the registry reports no dose determination. The description of planned escalation levels should not be mistaken for an achieved dose-finding result.
The trial also lists toxicity and tumor-response outcomes, as well as time-to-event outcomes for response and disease progression. The registry reports 14 outcome measures and zero analyses. The listed outcome names do not supply estimates, uncertainty intervals, or tests. No efficacy estimate, confidence interval, or p-value is reported in the registry record. Consequently, the posted information does not quantify a treatment effect or its precision.
Serious adverse-event figures are presented by dose group, with counts of participants at risk and affected. For example, the Phase 2 pemetrexed 500 + carboplatin AUC 6 group reports 66 at risk and 15 affected for serious adverse events. The Phase 1 groups report smaller at-risk counts, and affected counts differ by dose group. These are descriptive safety counts, not a randomized comparison. Differences between groups cannot be interpreted as causal dose effects from this non-randomized design.
The listed serious-event terms include percentages, such as Anaemia and Constipation at 33.3%, and Gastrointestinal haemorrhage at 25.0%. The registry record does not identify the denominator for those term percentages in the information recorded. They should therefore be read as listed serious-event percentages, not automatically as percentages of all enrolled participants or as comparative risks.
In general, a confidence interval describes the range of values compatible with an estimate under a statistical method and its assumptions. No confidence interval for the primary dose endpoint or the listed efficacy outcomes is reported in the registry record, so precision cannot be assessed from those measures. Likewise, no inferential analysis is listed. The record’s evidence is best read as a description of trial design, a primary endpoint not determined, and group-specific safety counts, without a reported efficacy comparison.
9. Statistical Methods Explained
What does the design allow?
The registry describes a non-randomized, unmasked, single-group trial with Phase 1 and Phase 2 components. In general, random allocation helps balance measured and unmeasured characteristics between treatment groups, while masking can reduce some forms of assessment or reporting bias. Neither feature is recorded for this trial. The Phase 1 dose groups are not randomized controls, and the Phase 2 cohort is not a concurrent comparator. Descriptive differences between dose groups can be reported, but they do not by themselves establish that dose caused a difference in outcomes.
How was the primary endpoint intended to be assessed?
The primary endpoint was the maximum tolerated dose of pemetrexed with carboplatin. The registry describes dose escalation based on the observed pattern of dose-limiting toxicity. If none of 3 initial participants at a dose level experienced a dose-limiting toxicity in Cycle 1, enrollment proceeded to the next dose level. If at least 2 participants experienced a dose-limiting toxicity in Cycle 1 at a dose level, that level was considered the maximum tolerated dose. The registry does not describe the decision rule for every possible pattern between those stated conditions; that detail is not reported in the registry record.
The record says the planned pemetrexed dose could increase up to 900 mg/m^2 and carboplatin AUC up to 6 mg/mL*min. It further states that, based on results from a different Phase 2 study, further dose escalations were not explored. Most importantly for interpretation, the registry reports that the maximum tolerated dose was not determined and that zero participants were analyzed for that endpoint. The planned algorithm and dose limits are protocol descriptions, not a measured endpoint result.
What do the adverse-event counts represent?
In general, a count of participants affected is a descriptive measure of how many people in a group had the specified event during the recorded assessment. Its interpretation depends on the definition of the event, follow-up, and the denominator used. The registry gives at-risk and affected counts for serious and other adverse events in each listed group. These counts can describe what was recorded in those groups, but without randomization they do not provide a controlled estimate of the effect of one dose compared with another.
The term percentages also need their denominator to be clear. The registry lists serious-event terms and percentages, but the relevant denominator is not reported in the registry record. The percentages should not be reinterpreted as overall trial incidence, nor compared across groups as though they were generated from a common randomized analysis, unless the denominator and method are established.
What would inferential statistics add?
In general, a point estimate gives a numerical summary of an outcome, while a confidence interval communicates its statistical uncertainty. A hypothesis test evaluates data against a specified null hypothesis under stated assumptions. Those methods require an estimand, an analysis population, a statistical model, and a definition of how missing observations are handled. The registry lists zero analyses, and it does not report estimates, confidence intervals, p-values, or a statistical analysis plan. No inferential conclusion can therefore be drawn from the endpoint names alone.
For count outcomes, methods may need to account for variability beyond that expected under a simple model. In general, over-dispersion means the observed variation exceeds the model’s assumed variation; ignoring it can make standard errors too small and confidence intervals too narrow. The registry does not identify a count model or report an analysis of this kind. This general consideration does not imply that over-dispersion occurred in this trial.
How should planning figures be understood?
In general, a sample-size calculation is a design aid based on assumptions about the effect to detect, significance level, allocation, and statistical method. The registry’s planning illustration is described as being computed from an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event outcomes, it uses a total number of events; for other outcomes, it gives participants per arm. It describes the target effect as a stated fraction of the observed effect.
These are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The registry record does not report the trial’s own sample-size justification. No planning output values are reported in the record details, so none can be interpreted as a recommended or achieved sample size. More generally, power calculated after observing a result does not establish the probability that the result is true or the probability that a treatment effect exists.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures, including primary and secondary outcomes across Phase 1 and Phase 2. When a study assesses many outcomes, the chance of at least one apparently notable finding can increase if each is tested separately. In general, multiplicity procedures can control error rates or prioritize a prespecified outcome hierarchy. The registry record does not report a multiplicity adjustment, a hierarchy for interpreting the outcomes, or an analysis plan. It also lists zero analyses, so there are no reported tests for which an adjustment can be evaluated.
The primary endpoint population is specifically described: the maximum tolerated dose was not determined, so zero participants were analyzed for that endpoint. The overall enrollment of 86 is not the same as an analyzed population for each outcome. Outcome-specific analysis populations, including the participants included in tumor-response and time-to-event analyses, are not reported in the registry record.
Missing-data methods and the amount or pattern of missing outcome data are not reported in the registry record. In general, missingness can affect estimates when participants with unavailable measurements differ from those with observed measurements. The impact depends on why data are missing and on the analysis method. Without reported denominators, follow-up details, or missing-data procedures, that impact cannot be assessed.
The registry also does not report whether interim analyses were planned or conducted. No interim-analysis procedure or stopping rule beyond the described dose-escalation criteria is reported in the registry record. The dose escalation description is not a substitute for a general interim efficacy-analysis plan.
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 |
|---|---|---|---|
| Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | 1 | 4 | 25.0% |
| Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | 0 | 3 | 0.0% |
| Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | 0 | 4 | 0.0% |
| Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | 0 | 3 | 0.0% |
| Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | 1 | 3 | 33.3% |
| Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) | 1 | 3 | 33.3% |
| Pemetrexed 500 + Carboplatin AUC 6 (Phase 2) | 15 | 66 | 22.7% |
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 |
|---|---|
| Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | 4 of 4 |
| Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | 3 of 3 |
| Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | 4 of 4 |
| Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | 3 of 3 |
| Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | 3 of 3 |
| Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) | 2 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) |
|---|---|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 1 of 3 | 0 of 3 |
| Constipation | Gastrointestinal disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 1 of 3 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Pancytopenia | Blood and lymphatic system disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Tachycardia | Cardiac disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Abdominal pain | Gastrointestinal disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Ascites | Gastrointestinal disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Ileus | Gastrointestinal disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
| Nausea | Gastrointestinal disorders | 0 of 4 | 0 of 3 | 0 of 4 | 0 of 3 | 0 of 3 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 4 of 4 | 2 of 3 | 3 of 4 | 3 of 3 | 3 of 3 | 2 of 3 |
| Vomiting | Gastrointestinal disorders | 2 of 4 | 2 of 3 | 4 of 4 | 3 of 3 | 3 of 3 | 1 of 3 |
| Fatigue | General disorders | 3 of 4 | 2 of 3 | 4 of 4 | 2 of 3 | 3 of 3 | 1 of 3 |
| Constipation | Gastrointestinal disorders | 4 of 4 | 2 of 3 | 2 of 4 | 3 of 3 | 1 of 3 | 2 of 3 |
| Headache | Nervous system disorders | 2 of 4 | 3 of 3 | 3 of 4 | 1 of 3 | 1 of 3 | 2 of 3 |
| Thrombocytopenia | Blood and lymphatic system disorders | 2 of 4 | 1 of 3 | 3 of 4 | 3 of 3 | 2 of 3 | 0 of 3 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 4 | 2 of 3 | 3 of 4 | 1 of 3 | 2 of 3 | 0 of 3 |
| Abdominal pain | Gastrointestinal disorders | 2 of 4 | 2 of 3 | 1 of 4 | 1 of 3 | 2 of 3 | 0 of 3 |
| Leukopenia | Blood and lymphatic system disorders | 0 of 4 | 2 of 3 | 2 of 4 | 1 of 3 | 2 of 3 | 0 of 3 |
| Flushing | Vascular disorders | 1 of 4 | 2 of 3 | 3 of 4 | 0 of 3 | 0 of 3 | 1 of 3 |
Serious events with the highest arm-level rate: anaemia (33.3%), constipation (33.3%), gastrointestinal haemorrhage (25.0%), drug hypersensitivity (4.5%), vomiting (3.0%).
The serious adverse-event figures are organized by dose group and phase. For Pemetrexed 500 + Carboplatin AUC 5 in Phase 1, 4 participants were at risk and 1 was affected. For Pemetrexed 600 + Carboplatin AUC 5, 3 were at risk and 0 were affected. For Pemetrexed 600 + Carboplatin AUC 6, 4 were at risk and 0 were affected. For Pemetrexed 700 + Carboplatin AUC 6, 3 were at risk and 0 were affected. For Pemetrexed 800 + Carboplatin AUC 6, 3 were at risk and 1 was affected. For Pemetrexed 900 + Carboplatin AUC 6, 3 were at risk and 1 was affected. In Phase 2, Pemetrexed 500 + Carboplatin AUC 6 had 66 at risk and 15 affected.
These are group-specific descriptive counts. The groups were not randomized controls, and their sizes differ. The counts do not establish that a dose caused more or fewer serious events. The registry lists Anaemia and Constipation at 33.3%, Gastrointestinal haemorrhage at 25.0%, Drug hypersensitivity at 4.5%, and Vomiting and Dyspnoea at 3.0% among the top serious-event terms. The denominator and calculation method for those term percentages are not reported in the registry record. Death counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record describes a completed trial combining pemetrexed and carboplatin in recurrent ovarian or primary peritoneal cancer. Its primary endpoint was a Phase 1 maximum tolerated dose, and that dose was not determined. Zero participants were analyzed for that primary endpoint. This is the main limit on what can be concluded about dose finding from the posted record.
The study’s Phase 1 dose-escalation description and the listed dose groups provide context for what was investigated, but they do not establish a recommended dose. The record states that further dose escalations were not explored based on results from a different Phase 2 study. That explanation does not substitute for an endpoint determination within this study.
The registry also lists tumor response and time-to-event outcomes, but it reports zero analyses. No effect estimate, confidence interval, or p-value for those outcomes is reported in the registry record. The presence of outcome names should not be read as evidence that an outcome was achieved or that the combination changed it. The information recorded does not allow a quantitative assessment of efficacy or the precision of an efficacy estimate.
The adverse-event counts and serious-event term percentages are descriptive. They can be read as recorded safety information for the stated groups, with the caveat that the term-percentage denominator is not reported in the registry record. Since the study was non-randomized and had no control group, these safety data do not provide a randomized comparison of risks between treatments.
In general, a completed trial may still leave its primary question unanswered in the registry record. Here, completion status indicates the study is recorded as completed; it does not imply that the maximum tolerated dose was determined or that an efficacy analysis was reported. The sound interpretation is therefore narrow: the trial investigated the combination across phases, but its recorded primary dose-finding outcome is undetermined and its efficacy analyses are not reported.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a study’s intended endpoint and the result actually reported for that endpoint. The Phase 1 primary question was a toxicity-guided maximum tolerated dose. The registry describes the escalation logic and the range of dose levels, but it explicitly says the dose was not determined and that zero participants were analyzed for the endpoint. A protocol description is not an endpoint estimate.
It also illustrates why design labels matter. Non-randomized dose groups can be useful for describing experience at different dose combinations, but they do not provide the exchangeability expected from randomized groups. Group-specific event counts should therefore not be treated as direct causal comparisons. The single-group designation and absence of masking also shape the scope of interpretation.
The record distinguishes overall enrollment from endpoint-specific analysis. Enrollment is 86, while the primary endpoint population is reported as zero. That difference is not a contradiction: the endpoint was not determined, and the study’s other outcomes may have different analysis populations, which are not reported in the registry record.
Finally, the record lists many outcomes but no analyses. This underscores the importance of estimates, denominators, uncertainty intervals, and clear analysis populations when interpreting clinical data. Without them, readers cannot quantify the magnitude or precision of efficacy outcomes, assess missingness, or determine how multiple outcomes were handled. The posted information supports a careful description of design and recorded safety counts, not a broad conclusion about treatment effects.
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 the trial’s main question is that the registry says the maximum tolerated dose was not determined. It reports zero participants analyzed for that endpoint, so no primary dose estimate is available. The listed dose levels and escalation criteria do not fill that gap.
The design was non-randomized, unmasked, and single-group, with no separate comparator reported. Phase 1 dose groups and the Phase 2 cohort cannot be treated as randomized treatment and control groups. The posted safety counts are descriptive, and apparent differences between groups cannot be attributed to dose from this design alone.
Although the registry lists response and time-to-event outcomes, it records zero analyses. Outcome estimates, confidence intervals, p-values, and the statistical analysis plan are not reported in the registry record. The outcome-specific analysis populations and missing-data methods are also not reported. The registry record does not report the denominator or calculation method for the listed serious-event term percentages, limiting their interpretation as rates.
Enrollment of 86 should not be taken as the denominator for every endpoint. The registry identifies zero participants for the primary endpoint analysis, and does not specify analyzed populations for the other outcomes in the information recorded. The sample-size justification, interim analyses, and multiplicity procedures are not reported in the registry record. The stated planning illustration is not the trial’s own design justification and should not be read as observed power.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial of Pemetrexed and Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer — NCT00489359.
- Registry record last updated 2011-06-16; status last verified 2011-05.
- Results first posted 2011-06-16.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry identifies NCT00489359 as a completed Phase 1 and Phase 2 trial of pemetrexed with carboplatin in recurrent ovarian or primary peritoneal cancer. The study was non-randomized, unmasked, and single-group, with enrollment of 86. Both drugs were administered intravenously on Day 1 of a 21-day cycle.
The primary endpoint was the Phase 1 maximum tolerated dose of pemetrexed with carboplatin. The registry states that it was not determined and that zero participants were analyzed for the endpoint. The record lists secondary toxicity, response, and time-to-event outcomes, but reports zero analyses. Serious adverse-event counts are provided by dose group; the denominator for the listed serious-event term percentages is not reported in the registry record. No randomized comparator or efficacy estimate is reported.