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 Alimta® Plus Cisplatin & Paclitaxel Given Intraperitonelly; First Line Tx Stage III Ovarian Cancer (NCT00702299), a na phase 1 study. The primary outcome is Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00702299 |
| Phase | Phase 1 |
| Condition | Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Arizona |
| Results posted | Yes |
2. Clinical Question
Population
Women with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer were the intended population. The registry lists ovarian cancer, fallopian tube cancer, and peritoneal cavity cancer among the conditions. Enrollment was 15.
Intervention
The study evaluated intraperitoneal pemetrexed disodium in a dose-escalation regimen with intraperitoneal cisplatin and paclitaxel. Pemetrexed was given on day 1, cisplatin on day 2, and paclitaxel on day 8. The regimen also included a biologic sample preservation procedure.
Comparator
There was no separate control group. The study is registered as a single-group trial with allocation listed as not applicable and no masking. Dose levels were escalated within the treatment group; they were not randomized treatment arms for a like-for-like comparison.
Primary question
The primary question was which pemetrexed dose could be given with the specified cisplatin and paclitaxel regimen while meeting the registry’s dose-limiting-toxicity rule. The record does not report the maximum tolerated dose identified or the observed dose-limiting toxicities by dose level.
This is a dose-finding question, not a randomized test of whether the regimen improves outcomes compared with another treatment. The study’s stated purpose was to examine side effects and the best dose of intraperitoneal pemetrexed in combination with intraperitoneal cisplatin and paclitaxel. Progression-free survival at 18 months, overall survival, and pemetrexed pharmacokinetics were also listed as secondary outcomes. Results for these outcomes are not reported in the registry record.
3. Trial Design
This was a phase I, open-label, single-group study. The registry lists enrollment of 15 and describes dose escalation across five pemetrexed dose levels, with three patients accrued to each level. The dose range was 60-1,000 mg/m2. The record does not provide the individual dose levels in that range. Intraperitoneal pemetrexed was scheduled for day 1, intraperitoneal cisplatin 75 mg/m2 for day 2, and intraperitoneal paclitaxel 60 mg/m2 for day 8.
In a single-group dose-escalation study, the central purpose is to observe tolerability at successive doses under a specified regimen. Here, the dose—not assignment to competing treatments—was varied. Allocation is listed as not applicable, and masking as none. Consequently, the study does not provide a concurrent control group for comparing outcomes or adverse events. The dose levels should not be read as randomized comparison arms.
The registry identifies the sponsor as the University of Arizona and gives the study status as completed. The recorded start was 2007-09, and primary completion was 2012-01. The primary outcome timeframe is listed as 18 months. The description of its decision rule refers to dose-limiting toxicity after the first cycle of therapy; how that rule relates to the stated timeframe is not explained in the registry record.
The record does not report the protocol’s full statistical analysis plan, eligibility criteria in detail, dose-escalation safeguards beyond the stated rule, or the reasons for the enrollment target. A sample-size justification is not reported in the registry record. The listed enrollment and dose-escalation structure describe the study’s scale, but they do not by themselves establish the precision of a dose estimate.
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 | Receiving Treatment |
|---|---|
| STARTED | 15 |
| COMPLETED | 15 |
| NOT COMPLETED | 0 |
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 | Receiving Treatment |
|---|---|---|
| Participants analysed | 15 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 |
| Age, Categorical: >=65 years | Participants | 9 |
| Age, Continuous | years | 61.73 (SD 9.76) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2), measured over 18 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/m2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of pemetrexed, expressed in mg/m2, when combined with day 2 intraperitoneal cisplatin 75 mg/m2 and day 8 intraperitoneal paclitaxel 60 mg/m2. It is a dose-finding endpoint: it aims to identify the pemetrexed dose that meets a toxicity-based rule in the context of this specific combination and schedule. It is not an endpoint measuring whether the regimen controls cancer or extends survival.
The registry’s rule says that if none of the initial three patients at a dose level experienced a dose-limiting toxicity after the first cycle, escalation proceeded to the next level. If two or more patients at any dose level experienced a dose-limiting toxicity, the maximum tolerated dose would be the next lower dose level. The record does not state the decision for a level at which exactly one patient experienced a dose-limiting toxicity, nor does it report the observed toxicities or selected dose.
Maximum tolerated dose is used in early-phase studies to guide dose selection using tolerability observed under a defined regimen. The result depends on the toxicity definition, observation period, dose sequence, and escalation rules. The endpoint’s timeframe is listed as 18 months, while the rule specifically refers to the first cycle; further operational details are not reported in the registry record. No numerical primary endpoint result is reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed phase I dose-escalation study, but it does not post a result for the primary endpoint. In particular, the maximum tolerated dose is not reported in the registry record. Without dose-level toxicity results, the escalation rule cannot be applied independently to identify which dose met the study’s criterion. The listed dose range and planned regimen describe the design, not the observed outcome.
This distinction matters because a dose-finding study does not answer the same question as a comparative efficacy trial. Its primary question concerns dose and tolerability in the enrolled group under the specified schedule. The registry lists progression-free survival at 18 months as assessed by cancer antigen 125, overall survival, and pemetrexed pharmacokinetics among secondary outcomes, but outcome estimates for these measures are not reported in the registry record. No treatment-effect estimate or between-group contrast is available from the described single-group design.
General statistical interpretation: an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the data under the statistical model and its assumptions. In a small dose-escalation study, estimates can be imprecise, and observed toxicity at a dose may not precisely represent toxicity in a wider population. The registry record does not report a confidence interval or another uncertainty measure for the primary endpoint.
The record lists six outcome measures and zero analyses. It does not provide a results analysis for the primary endpoint or the named secondary outcomes. Thus, the posted information supports a description of the planned question and regimen, but not a conclusion about the dose selected, the frequency of dose-limiting toxicity at each dose, or the pattern of secondary outcomes. These results are not reported in the registry record.
Because the study has no control group, observed outcomes would not by themselves establish what would have happened under another regimen or no treatment. General statistical explanation: a control group helps distinguish changes associated with an intervention from changes related to other influences, although it does not eliminate every source of uncertainty. Here, the registry’s design is suited to describing a dose-escalation study, not to estimating a randomized treatment contrast.
Any planning illustration based on an observed effect is distinct from an analysis of the trial’s observed outcomes. The record’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a fraction of the observed effect. Those assumptions do not convert this single-group study into a two-arm trial, and a planning calculation is not observed power. No results for such a planning calculation are needed to interpret the registry’s unreported primary endpoint.
9. Statistical Methods Explained
General explanation: phase I dose escalation is designed to learn about tolerability as dose changes, rather than to make a definitive comparison of clinical benefit. The interpretation depends on the dose levels tested, the definition and timing of dose-limiting toxicity, and the rule for moving between dose levels. In this study, the registry describes five pemetrexed dose levels, three patients accrued at each level, and a decision rule based on toxicities after the first cycle. The individual dose levels and observed toxicity counts at each level are not reported in the registry record.
What does the escalation rule mean?
The record states that escalation proceeds if none of the initial three patients at a dose level experiences a dose-limiting toxicity after the first cycle. If two or more patients at any dose level experience a dose-limiting toxicity, the maximum tolerated dose is determined to be the next lower dose level. This is the decision rule as registered; it does not provide enough detail to resolve every possible pattern. In particular, the rule for exactly one dose-limiting toxicity among the initial three patients is not reported in the registry record. Nor does the record give the observed dose-limiting toxicities needed to apply the rule.
General explanation: a rule based on a small group at each dose can guide escalation, but the result is inherently dependent on which patients are observed and how toxicity is defined. A maximum tolerated dose selected under a rule is an operational study result, not a guarantee that every patient will experience the same tolerability. The registered dose range, 60-1,000 mg/m2, does not identify the selected dose.
Why does the single-group design matter?
The study has one treatment group and no masking. Dose levels were part of the escalation process, not randomized comparison groups. General explanation: randomization supports balanced comparisons by assigning participants to different interventions through a chance process. Without that structure and a concurrent control group, differences across dose cohorts can reflect factors other than dose. In this study, the main registered aim is to select a dose using a toxicity rule, rather than to estimate a causal contrast between treatment strategies.
The registry lists allocation as not applicable and identifies the model as single group. It does not report a control regimen. The design therefore cannot supply a direct comparison of the combination regimen against another treatment. The absence of a comparator also limits interpretation of secondary outcomes such as progression-free survival and overall survival: without a control group, the record cannot establish how those outcomes compare with another course of care.
What can be learned from uncertainty measures?
General explanation: a point estimate gives a single summary of an observed quantity, while an uncertainty interval communicates how variable that estimate may be under a statistical model. A narrow interval indicates greater precision than a wide interval, although precision does not remove possible bias or guarantee generalizability. Dose-finding results are more useful when the estimate is accompanied by its uncertainty and by the underlying toxicity counts. The registry record does not report the primary endpoint estimate, interval, or dose-level counts, so precision cannot be assessed from the posted primary outcome information.
General explanation: over-dispersion occurs when observed variability is greater than a model expects. If a model assumes less variability than is present, its uncertainty estimates may be too small and its intervals too narrow. The registry does not report a model-based dose-response analysis or a dispersion assessment, so there is no basis to characterize either for this study.
How should planning calculations be distinguished from trial results?
General explanation: a sample-size calculation is a planning exercise based on assumptions about the outcome, effect, allocation, and analysis. It does not measure the power achieved after a study is completed. The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also specifies that time-to-event calculations use the total number of events, while other calculations use participants per arm. These are planning conventions, not features that change the registered study’s single-group design.
The record does not report the trial’s own sample-size justification. A planning illustration based on an observed effect should not be interpreted as observed power or as evidence that the study could reliably establish a treatment effect. General explanation: power depends on the assumed effect and variability, as well as the analysis design; an observed effect may itself be unstable, particularly in a small study. No such calculation can substitute for the missing primary endpoint and outcome results.
What analysis details remain unavailable?
The registry record lists six outcome measures and zero analyses, but does not report a full statistical analysis plan. The handling of missing data, the analysis population for each outcome, the statistical model for pharmacokinetics, any adjustment for covariates, and the approach to repeated or multiple outcomes are not reported in the registry record. These omissions prevent a detailed audit of how the outcomes were intended to be analyzed or how reported estimates would have been derived.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures. It names progression-free survival at 18 months as assessed by cancer antigen 125, overall survival, and pemetrexed pharmacokinetics (mean Cmax, ug/mL) for different dosages as secondary outcomes. The primary outcome is maximum-tolerated dose. The remaining outcome details and the results for the listed outcomes are not reported in the registry record.
When a study evaluates multiple outcomes or makes multiple statistical comparisons, the chance of obtaining a seemingly notable result by chance can increase. General explanation: multiplicity methods may control that risk, but the appropriate method depends on which outcomes and comparisons are considered confirmatory and how they are related. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an adjustment procedure. It also lists zero analyses, so no analysis results or adjustment decisions are posted.
Missing-data methods and analysis populations are not reported in the registry record. The record does not state how participants with incomplete follow-up, unevaluable toxicity, or missing measurements would be handled, nor does it specify whether outcomes were analyzed in all enrolled participants or another defined population. These details matter because excluding participants or handling missing measurements differently can alter the interpretation of estimates. No assumptions about the handling of missing data can be inferred from the dose-escalation description alone.
The registry’s stated dose rule is specific about some toxicity patterns but does not describe the decision for exactly one dose-limiting toxicity among the initial three patients. This is a separate design detail from multiplicity and missing-data handling; both are relevant to reproducibility, and neither is fully addressed in 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 |
|---|---|---|---|
| Receiving Treatment | 5 | 15 | 33.3% |
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 |
|---|---|
| Receiving Treatment | 13 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Receiving Treatment |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 2 of 15 |
| Mortality | General disorders | 1 of 15 |
| Upper Respiratory | Respiratory, thoracic and mediastinal disorders | 1 of 15 |
| Small Bowel Obstruction | Gastrointestinal disorders | 1 of 15 |
| Unknown Hospitalization not required | General disorders | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Receiving Treatment |
|---|---|---|
| Fatigue | General disorders | 3 of 15 |
| Other-Skin | Skin and subcutaneous tissue disorders | 3 of 15 |
| Anoxeria | Psychiatric disorders | 3 of 15 |
| Diarrhea | Gastrointestinal disorders | 2 of 15 |
| Nausea | Gastrointestinal disorders | 2 of 15 |
| Oral Mucositis | Gastrointestinal disorders | 2 of 15 |
| Vomiting | Gastrointestinal disorders | 2 of 15 |
| Anemia | Blood and lymphatic system disorders | 2 of 15 |
| Leukopenia | Blood and lymphatic system disorders | 2 of 15 |
| Neutropenia | Blood and lymphatic system disorders | 2 of 15 |
Serious events with the highest arm-level rate: diarrhea (13.3%), mortality (6.7%), upper respiratory (6.7%), small bowel obstruction (6.7%), unknown hospitalization not required (6.7%).
The registry reports that 5 of 15 participants were at risk for serious adverse events and were recorded as affected; it reports that 13 of 15 were at risk for other adverse events and were recorded as affected. These are participant-level group summaries. They do not describe the severity, timing, duration, recurrence, or relationship to a particular dose for each event.
The listed top serious adverse event terms are diarrhea, 13.3%; mortality, 6.7%; upper respiratory, 6.7%; small bowel obstruction, 6.7%; and unknown hospitalization not required, 6.7%. The registry record does not provide event counts by dose level or explain the detailed coding and grouping behind these terms. The death count is not reported in the registry record. The term mortality in the list should therefore be read as a reported adverse-event term, not as a complete account of deaths or their causes.
General explanation: adverse-event summaries describe events recorded during a study; they do not by themselves establish that the study treatment caused an event. In a single-group study, there is no concurrent control group for estimating how event rates compare with another regimen. These summaries also cannot show whether risk differs across the pemetrexed dose levels without dose-specific data. The registry does not report those dose-specific safety results.
12. What the Result Does, and Does Not, Mean
The study addresses an important early-phase statistical task: selecting a pemetrexed dose for use with intraperitoneal cisplatin and paclitaxel under a registered toxicity rule. It documents the intended population, schedule, dose range, and escalation approach. The registry record does not report the selected maximum tolerated dose, observed dose-limiting toxicities by dose, or outcome estimates for the named secondary measures.
That absence limits what can be concluded from the posted information. The study’s completed status does not itself establish that its primary question was answered in the public record. The listed enrollment of 15 and the plan to accrue three patients to each of five dose levels describe the study structure, but do not reveal the observed toxicity pattern or the precision of any dose estimate.
The design also does not support a controlled comparison of treatment effects. As a single-group, open-label study with allocation listed as not applicable, it has no randomized comparator. Even if survival or tumor-marker outcomes had been reported, a single-group result would describe outcomes in the enrolled participants, not the difference caused by treatment relative to another strategy. Those secondary results are not reported in the registry record.
General explanation: statistical conclusions depend both on the data and on the design that generated them. A dose-finding rule can organize decisions about escalation, while a randomized comparative design addresses a different question. Neither design makes results automatically applicable beyond the studied participants and treatment schedule. Here, the registry record does not provide enough outcome detail to assess the dose decision or its uncertainty.
The appropriate reading is therefore limited: the record describes a phase I dose-escalation study and reports group-level adverse-event summaries, but does not report the primary dose result or detailed outcome analyses. It does not establish whether the regimen is effective, ineffective, or preferable to another treatment. Those claims cannot be drawn from the posted information.
13. Why This Trial Matters Statistically
This trial illustrates how a clinical study’s statistical question follows from its design. A phase I, single-group dose-escalation study is structured around tolerability and dose selection, rather than a randomized comparison of clinical outcomes. Keeping that distinction clear prevents a dose-finding study from being interpreted as if it were an efficacy trial.
The registered escalation rule also shows why operational detail matters. The rule specifies what happens when none of the initial three patients at a dose level has a dose-limiting toxicity and when two or more have one. It does not specify the outcome for exactly one such toxicity. Reporting the full decision algorithm and the observed results at each dose would allow readers to understand how the maximum tolerated dose was selected and how robust that decision may be.
General statistical explanation: a transparent report connects the design, endpoint definition, analysis population, observed data, and uncertainty estimate. When these elements are available, readers can distinguish the intended decision rule from the result obtained and assess how much information supports that result. The registry record lists the intended dose range and some adverse-event summaries, but does not report the primary dose estimate, dose-level toxicity counts, or an uncertainty measure.
The record also underscores that adverse-event summaries and clinical outcome analyses answer different questions. Event counts can describe safety observations, while a controlled comparison is needed to estimate a treatment contrast. The posted safety summaries do not supply a comparison, and the named secondary outcome results are not reported in the registry record.
For biostatisticians and clinical researchers, the key statistical lesson is to align interpretation with the design and the completeness of reporting. The registered objective can be described, but conclusions about the selected dose or outcomes require results that the registry record does not report.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpretation is that the registry record does not report the primary endpoint result. The selected maximum tolerated dose, dose-limiting toxicity counts by level, and the evidence used to apply the escalation rule are not reported. The dose range of 60-1,000 mg/m2 is not a substitute for the actual dose sequence or the selected dose.
The dose-escalation description leaves a decision-rule detail unresolved: it does not state what happens when exactly one of the initial three patients at a level experiences a dose-limiting toxicity. The dose-limiting toxicity definition and additional assessment details are not reported in the registry record. The timeframe is listed as 18 months, while the rule refers to toxicity after the first cycle; the relationship between these descriptions is not explained.
Enrollment was 15, and the study was single group and open label. There is no control group for a like-for-like comparison, and dose levels were not randomized treatment arms. The record does not report detailed eligibility criteria, participant disposition, baseline characteristics, or dose-specific adverse-event results. These omissions constrain assessment of who contributed data and how representative the enrolled group may be.
Analysis details are also limited. The registry record does not report the statistical analysis plan, analysis populations, missing-data methods, multiplicity approach, or uncertainty estimates. It names secondary outcomes but does not report their results. The serious adverse event summary includes top terms, but the death count is not reported, and the record does not provide event timing, dose level, or a causal assessment for those terms.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Alimta® Plus Cisplatin & Paclitaxel Given Intraperitonelly; First Line Tx Stage III Ovarian Cancer — NCT00702299.
- Registry record last updated 2016-01-01; status last verified 2015-12.
- Results first posted 2013-07-19.
- 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.
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18. Record Summary
NCT00702299 is a completed phase I, open-label, single-group study sponsored by the University of Arizona. The recorded start was 2007-09, and primary completion was 2012-01. Enrollment was 15. The study examined dose escalation of intraperitoneal pemetrexed with intraperitoneal cisplatin and paclitaxel for women with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.
The primary outcome was maximum-tolerated dose of pemetrexed with the specified cisplatin and paclitaxel schedule. The registry describes escalation across five dose levels, with three patients accrued per level, within a dose range of 60-1,000 mg/m2. The selected maximum tolerated dose and dose-level toxicity results are not reported in the registry record.
Named secondary outcomes include progression-free survival at 18 months, overall survival, and pemetrexed pharmacokinetics. Their results are not reported in the registry record. The record lists serious and other adverse-event summaries but does not report the death count.