Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer (NCT01188876), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD).

2. Clinical Question

The registry describes a Phase I/II investigation. Its primary outcome is a dose-finding question rather than a direct comparison of treatment outcomes between groups. The rationale in the record proposes that pralatrexate might enhance carboplatin’s antitumor effect, and describes the research aim as finding the highest pralatrexate dose that can be given safely in combination with carboplatin. That rationale is not itself evidence of a treatment effect.

The registered primary outcome is maximum tolerated dose, measured in mg/m^2, with a timeframe of 1 year. The dose-escalation rules describe how dose-limiting toxicities would guide decisions about advancing, adding participants at a dose level, or treating a preceding dose as the MTD. The registry record does not report the resulting MTD or the dose-limiting toxicity observations used to determine it. Overall survival, progression-free survival, treatment-related adverse events and drug concentration measures are listed as secondary outcomes, but their results are not detailed in the record details.

3. Trial Design

The registry record describes a completed Phase I/II study sponsored by Massachusetts General Hospital. The recorded study start is 2010-08, and primary completion is recorded as 2016-07. Enrollment is listed as 50. The conditions named are ovarian cancer, fallopian tube cancer and peritoneal cancer; the study title and primary outcome description further specify recurrent platinum-sensitive disease.

The design is classified as single group, with allocation listed as NA and masking listed as none. These details matter for interpretation: the record does not identify a separate control arm, and it does not support a randomized comparison. The combination named in the study title and arm description is carboplatin and pralatrexate. Folic acid and vitamin B12 injection also appear in the interventions list, but their role in the regimen is not described in the record details.

The primary outcome is the maximum tolerated dose of pralatrexate in combination with carboplatin. Its stated timeframe is 1 year, and the population for this outcome is participants in the Phase I dose-escalation portion. The registry describes a standard 3 + 3 escalation approach, with starting dose and escalation rules set out in the primary outcome description. The record does not report the observed dose level identified as the MTD.

Secondary outcomes include overall survival, progression-free survival, treatment-related adverse events, maximum concentration of drug in plasma and area under the plasma drug concentration-time curve. Seven outcome measures are recorded, while the number of analyses is 0. The record does not detail results for the listed secondary outcomes beyond the adverse-event summaries. The statistical analysis plan, recruitment flow, and details about how participants entered the Phase I and Phase II portions 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

Analysis population for the primary outcome, as defined in the registry: The participants that participated in the phase 1 dose escalation portion of the study

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 Maximum Tolerated Dose (MTD), measured over 1 year.

The primary endpoint is maximum tolerated dose (MTD), expressed in mg/m^2. It asks how high the pralatrexate dose can be taken in combination with carboplatin under the study’s dose-escalation rules. This is a dose-finding endpoint: the object is to identify a dose level based on dose-limiting toxicity observations, not to estimate a difference in clinical outcomes between randomized groups.

The registry describes a 3 + 3 escalation approach. Participants begin at a stated pralatrexate dose, and dose increases are guided by whether dose-limiting toxicities occur after a full cycle. If a dose-limiting toxicity is observed among the initial participants at a level, additional participants may be enrolled at that level. The stated rules also define when a preceding dose is considered the MTD and when escalation stops. The primary outcome timeframe is 1 year.

In general, a maximum tolerated dose is used in early-phase research to summarize a dose-escalation decision under a specified toxicity rule. It should not be read as proof that the dose is effective, optimal for every participant, or free of risk. The registry record does not report the MTD value, the dose-limiting toxicity data behind the decision, or a confidence interval for the endpoint. Therefore, the endpoint’s result and its precision cannot be assessed from the record details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the dose-escalation rule do?

The primary outcome description specifies a 3 + 3 dose-escalation cohort. The starting pralatrexate dose is 30 mg/m2. If no dose-limiting toxicities are experienced after a full cycle, 3 additional participants are enrolled at the next highest dose level. Each increase raises the pralatrexate dose by 15 mg/m2. If 1 participant out of 3 develops a dose-limiting toxicity, 3 additional participants are added at that dose level. If 2 out of 3 experience a dose-limiting toxicity, the preceding dose is considered the MTD. If 1/6 has a dose-limiting toxicity, the next higher level begins accrual unless the study is at level +5, when Phase I accrual stops. If 2 or more of 6 participants have a dose-limiting toxicity, the preceding dose is considered the MTD.

In general, a rule-based escalation design uses observed toxicities at each dose level to determine whether escalation continues. The MTD is consequently a decision produced by the specified rule and the observed dose-limiting toxicity pattern. It is not an estimate of an average treatment effect, and it does not directly compare the regimen with an alternative. The registry gives the decision rules but does not report the observed dose-level outcomes or the resulting MTD.

How should a single-group design be read?

The study is recorded as single group, with allocation listed as NA and masking as none. In general, a single-group study can describe outcomes observed among participants receiving the study regimen. Without a separate control group, it cannot directly estimate how those outcomes differ from outcomes under another treatment. Changes over time or event frequencies in a single group do not by themselves distinguish treatment effects from other possible explanations. This is particularly relevant to the registry’s rationale about a possible antitumor effect: that rationale is not a comparative estimate.

Because there is no registered control comparison, a calculation framed as a difference between two arms would not represent the study’s design. The sample-size assumptions described for the planning illustrations refer to equal allocation between two arms, a two-sided significance level of 0.05, a normal approximation and an effect set as a fraction of an observed effect. In general, those are planning assumptions used to illustrate what a future comparison might require. They are not observed power, and they do not turn this single-group study into a comparative trial. The registry record does not report an observed effect estimate for such a comparison.

What can event counts and percentages establish?

The adverse-event summary provides participants at risk and affected for serious and other adverse events, along with deaths and selected serious-event terms and percentages. In general, counts describe how many participants were recorded as affected under the registry’s event definitions, while percentages describe proportions as recorded. These summaries can characterize reported events, but they do not alone show whether an event was caused by treatment or whether its frequency differs from another regimen. The record details do not give the event definitions, follow-up completeness, severity grades, or causal assessments for the listed terms.

Statistical uncertainty is also relevant to event summaries. In general, estimates from a study are subject to sampling variability, and an interval estimate can convey some of that uncertainty. The registry entries do not give confidence intervals for the adverse-event percentages or for the MTD. Without those intervals and without fuller event details, the precision of the reported summaries cannot be assessed from the record.

What does the analysis record tell readers?

Seven outcome measures are recorded, and the number of analyses is 0. The listed outcomes include the primary MTD endpoint and secondary outcomes for overall survival, progression-free survival, treatment-related adverse events, maximum concentration of drug in plasma and area under the plasma drug concentration-time curve. The outcome list indicates what was registered for assessment; it does not supply the results or the analysis methods for those outcomes. The statistical plan, including any model choices, adjustment methods, or interim analyses, is not reported in the registry record.

In general, analysis methods should be matched to the type of outcome. A dose-finding endpoint is interpreted through its escalation rule; time-to-event outcomes such as overall survival and progression-free survival require information about event times, censoring and the analysis method; and pharmacokinetic outcomes require their own measurement and summary procedures. The record details do not describe those procedures or provide results for these secondary endpoints. No model or inferential method should therefore be attributed to the trial beyond the dose-escalation rules explicitly described.

The registry lists the primary outcome timeframe as 1 year and identifies the MTD population as participants who participated in the Phase I dose-escalation portion. The size and composition of that endpoint-specific population are not reported in the registry record. Overall enrollment is recorded as 50, but that figure alone does not establish how many participants contributed to each outcome or analysis.

10. Multiplicity, Missing Data and Analysis Populations

The record lists seven outcome measures, including MTD as the primary outcome and several secondary outcomes: overall survival, progression-free survival, treatment-related adverse events, maximum concentration of drug in plasma and area under the plasma drug concentration-time curve. The number of analyses is recorded as 0. The registry record does not report how multiple outcomes or multiple analyses were handled, whether any multiplicity adjustment was planned, or which results were designated as confirmatory.

In general, testing or emphasizing several outcomes can increase the chance that an apparently notable finding arises by chance. Prespecified priorities and suitable multiplicity methods can help readers understand how results should be interpreted. Since the analysis plan and outcome results are not reported in the record details, no multiplicity strategy can be attributed to this study. The listed outcomes should not be treated as though each had a reported, independently confirmed result.

Missing-data methods are not reported in the registry record. The record details do not state how missing outcome measurements, incomplete follow-up, withdrawal, or unavailable event information were handled. Nor do they describe imputation, censoring rules, or sensitivity analyses. The absence of those details limits assessment of whether missing information could affect outcome summaries.

The primary outcome description identifies the relevant population as participants in the Phase I dose-escalation portion. The registry does not report the endpoint-specific analysis population size or define analysis populations for the secondary outcomes. Overall enrollment is 50, but it should not be assumed that every enrolled participant contributed to every endpoint. How Phase I and Phase II participants were included in each analysis is not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (4.0%), thrombocytopenia (4.0%), thromboembolytic event (2.0%), mucositis oral (2.0%), dyspepsia (2.0%).

The registry’s adverse-event summary lists 50 participants at risk for serious adverse events and 4 affected. For other adverse events, it lists 50 at risk and 50 affected. Deaths are listed as 0. These are the recorded summary figures for the Carboplatin/Pralatrexate group; they are not a comparison with another treatment group.

The registry also lists serious-event terms with percentages: Febrile Neutropenia, 4.0%; Thrombocytopenia, 4.0%; Thromboembolytic event, 2.0%; Mucositis Oral, 2.0%; and Dyspepsia, 2.0%. These entries describe the terms and percentages as recorded. They do not provide a complete account of all events or indicate, by themselves, that a particular event was caused by the regimen. The record details do not give event timing, duration, severity grading, or the methods used to assess relatedness.

In general, a serious adverse event classification is distinct from the broader category of adverse events. The two summaries should not be interchanged or interpreted as if they were the same endpoint. Counts and percentages describe recorded observations; they do not establish comparative safety, and they do not show how precisely the underlying event frequency is known. No confidence intervals for these safety summaries are reported in the registry record.

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

The study addresses a dose-finding question for pralatrexate combined with carboplatin in recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer. Its registry record describes the design, the primary endpoint and the escalation rules. It also reports adverse-event summary figures. However, the registry record does not report the MTD result, which is the primary outcome, so the dose selected by the study cannot be stated from these registry entries.

The record also does not report results for the listed overall survival, progression-free survival or pharmacokinetic outcomes. The absence of those results in the registry record does not establish what the outcomes were; it means their findings cannot be assessed from the information recorded. The adverse-event summaries can be described as recorded, but they do not show a comparison with another regimen or establish causality.

The single-group design has an important interpretive boundary. It can provide observations from the group treated in the study, but the registry does not identify a control group for estimating a treatment contrast. The research rationale that pralatrexate might improve carboplatin’s antitumor effect is a hypothesis, not evidence that the combination did so. No conclusion about comparative effectiveness follows from the design or the rationale alone.

In general, a point estimate is more informative when accompanied by an uncertainty measure and adequate details about the population and analysis. The record details do not provide a numerical MTD, confidence interval, or analysis results for the clinical secondary outcomes. The endpoint timeframe and escalation rules help define the question, but they cannot substitute for the observed result. The adverse-event figures likewise need context such as event definitions and follow-up to support a fuller interpretation; these details are not reported in the registry record.

The appropriate reading is therefore bounded: the record documents a completed Phase I/II, single-group investigation with a stated dose-escalation approach and reported safety summaries, but it does not provide the primary endpoint result or a comparative efficacy analysis. It neither establishes that the regimen works nor establishes that it does not work. It also does not show that the regimen is free from risk.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is dose finding, not a randomized treatment comparison. The registered MTD endpoint and the 3 + 3 escalation rules describe a decision process based on dose-limiting toxicities. Reading the study through that framework helps distinguish the intended Phase I question from claims about clinical benefit. A dose selected under a toxicity rule is not, by itself, evidence of an antitumor effect.

The registry design is single group, with allocation listed as NA and masking as none. Those features set a clear boundary on what can be estimated: the record does not provide a control group for a like-for-like comparison. This matters when interpreting the stated rationale that pralatrexate might enhance carboplatin’s effect. Statistical interpretation must separate the rationale for conducting a trial from the evidence its reported outcomes can support.

The record also illustrates why outcome registration and outcome reporting are different. Seven outcome measures are listed, but the number of analyses is 0, and the primary MTD result is not reported in the registry record. Knowing the endpoint and its timeframe clarifies what investigators intended to assess; without results and analysis details, it does not establish the answer.

Finally, safety summaries are informative but limited. The record reports serious-event and other-event summaries, deaths, and selected serious-event terms. In general, such figures describe recorded observations, while uncertainty, event definitions and comparative context affect how far they can be interpreted. The registry does not supply those details in the record details. This combination of a defined dose-escalation method, a single-group design and incomplete outcome reporting makes the distinction between design, observation and inference especially important.

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 study’s central question is that the registry record does not report the MTD result. It describes the escalation scheme but does not provide the dose-level observations or toxicity pattern needed to verify how the dose decision was reached. The primary outcome timeframe is stated as 1 year, but no endpoint estimate or uncertainty measure is reported.

The single-group design has no recorded comparator, so the study does not support a like-for-like treatment comparison. Masking is listed as none. These design features do not erase the value of describing dose-finding observations, but they limit what can be concluded about comparative outcomes. The record’s proposed antitumor rationale should not be confused with an efficacy result.

Outcome reporting is also limited in the record details. Seven outcome measures are registered, while the number of analyses is 0. Results for overall survival, progression-free survival and the pharmacokinetic outcomes are not detailed. Analysis methods, multiplicity handling, missing-data procedures, interim analyses and the statistical plan are not reported in the registry record. The number of participants contributing to each endpoint is also not reported.

The adverse-event summary gives at-risk and affected figures, deaths, and selected serious-event terms with percentages, but not event timing, duration, grading, relatedness assessments, or uncertainty intervals. These omissions restrict detailed interpretation of the safety summaries. Enrollment is listed as 50, but the record does not establish that all enrolled participants contributed to each outcome. The planning assumptions described for illustrations involve two-arm equal allocation, whereas the registered design is single group; such illustrations should not be read as trial results or as observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer — NCT01188876.
• Registry record last updated 2018-01-19; status last verified 2017-12.
• Results first posted 2018-01-19.
• 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

The registry record describes NCT01188876, a completed Phase I/II study sponsored by Massachusetts General Hospital. The study concerns carboplatin and pralatrexate in recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer. It is recorded as single group, with allocation listed as NA and masking listed as none. Enrollment is 50; the recorded start is 2010-08 and primary completion is 2016-07.

The primary outcome is maximum tolerated dose of pralatrexate in combination with carboplatin, with a timeframe of 1 year and a 3 + 3 escalation description. The record lists seven outcome measures and 0 analyses. It reports adverse-event summaries, including 4 affected for serious adverse events among 50 at risk, 50 affected for other adverse events among 50 at risk, and deaths listed as 0. The primary MTD result and detailed results for the listed clinical secondary outcomes are not reported in the registry record.