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 Topotecan and Gefitinib (Iressa) for Ovarian, Peritoneal, or Fallopian Tube Cancer (NCT00317772), a na phase 1, phase 2 study. The primary outcome is Dose Limiting Toxicity (DLT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00317772 |
| Phase | Phase 1, Phase 2 |
| Condition | Ovarian Cancer, Peritoneal Neoplasms, Fallopian Tube Cancer |
| Allocation | Not applicable (single group) |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with relapsed, platinum-resistant ovarian, peritoneal, or fallopian tube cancer whose tumors were epidermal growth factor receptor positive at least 1+. The registry record describes this population in the study summary; further eligibility details are not reported in the registry record.
Intervention
Weekly intravenous topotecan combined with daily oral gefitinib. In Phase I, topotecan dose levels were 2.0, 3.0, or 4.0 mg/m^2 on Days 1, 8, and 15 of a 28 day cycle, with gefitinib 250 mg daily. Phase II used the maximum tolerated dose from Phase I with gefitinib 250 mg daily for 28 Days.
Comparator
No randomized comparator is listed. The record describes a sequential study with a Topotecan + Gefitinib arm, not a like-for-like control comparison. Therefore, the posted information does not provide a randomized estimate comparing the combination against another treatment or control.
Primary question
The primary outcome concerns the number of dose-limiting toxicities, defined as any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity. The study summary also describes determining the maximum tolerated weekly topotecan dose with standard-dose gefitinib. The registry record does not report the primary outcome result or a maximum tolerated dose result.
The study also aimed to assess response rate and response duration in the described population treated at the maximum tolerated dose. Response Rate is listed as a secondary outcome. Its result, response duration results, and further details of how response was assessed are not reported in the registry record. The study question is therefore primarily a dose-finding and tolerability question, accompanied by planned assessment of tumor response. The posted record identifies the treatment schedule and the toxicity definition, but does not provide the outcome estimates needed to characterize those results.
3. Trial Design
The registry record identifies this as a Phase I/II study and lists M.D. Anderson Cancer Center as the sponsor. Its status is completed. The recorded start date is 2004-09-02, and the primary completion date is 2020-11-04. Enrollment is 19. Allocation is listed as NA, masking as none, and the model as sequential. The record does not describe a randomized control group; its listed arm is Topotecan + Gefitinib.
The Phase I schedule used intravenous topotecan on Days 1, 8, and 15 of a 28 day cycle at dose levels of 2.0, 3.0, or 4.0 mg/m^2. Gefitinib was given orally at 250 mg daily. For Phase II, the topotecan starting dose was the maximum tolerated dose from Phase I, given on the same days of the 28 day cycle; gefitinib was 250 mg by mouth daily for 28 Days. The registry record does not report which topotecan dose was selected as the maximum tolerated dose.
The primary outcome is Dose Limiting Toxicity (DLT), recorded as a number of dose-limiting toxicities. The listed timeframe is continual reassessment prior to each 28 day cycle, with an average of 60 days. The study summary describes determining dose-limiting toxicity and the maximum tolerated dose, then assessing response rate and response duration at that dose. Response Rate is listed as a secondary outcome. The registry record does not report the detailed protocol, the dose-assignment sequence, the planned sample-size justification, or the complete statistical analysis plan.
Because allocation is not randomized and there is no listed control arm, the design does not support a direct randomized comparison with another treatment. The sequential dose levels and expansion phase serve different roles within the described study; their participants should not be treated as if they formed independent randomized treatment groups. The registry record does not provide enough detail to reconstruct all enrollment decisions or the analysis populations.
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 | Phase 1 Dose Level 1 | Phase 1 Dose Level 2 | Phase 1 Dose Level 3 | Expansion Phase |
|---|---|---|---|---|
| STARTED | 3 | 3 | 3 | 10 |
| COMPLETED | 1 | 1 | 2 | 1 |
| NOT COMPLETED | 2 | 2 | 1 | 9 |
Reasons for not completing this period:
| Reason | Phase 1 Dose Level 1 | Phase 1 Dose Level 2 | Phase 1 Dose Level 3 | Expansion Phase |
|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 2 |
| Disease Progression | 2 | 2 | 1 | 7 |
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 | Phase 1 Dose Level 1 | Phase 1 Dose Level 2 | Phase 1 Dose Level 3 | Expansion Phase | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 3 | 10 | 19 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 2 | 1 | 7 | 13 |
| Age, Categorical: >=65 years | Participants | 0 | 1 | 2 | 3 | 6 |
| Age, Continuous | years | 55 (46 to 65) | 55 (42 to 76) | 68 (61 to 74) | 60 (47 to 71) | 60 (42 to 76) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 3 | 10 | 19 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 3 | 9 | 18 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 3 | 3 | 3 | 7 | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 1 | 1 |
| Region of Enrollment: United States | participants | 3 | 3 | 3 | 10 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Dose Limiting Toxicity (DLT), measured over Continual reassessment method, prior to each 28 day cycle, an average of 60 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Dose Limiting Toxicities |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of dose-limiting toxicities. The registry definition counts any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity as a DLT. The timeframe is described as assessment by the continual reassessment method prior to each 28 day cycle, over an average of 60 days. The endpoint is relevant to the dose-finding purpose because the study sought to identify the maximum tolerated weekly topotecan dose when combined with daily gefitinib.
In general, a dose-limiting toxicity rule translates observed harms into a prespecified outcome that can inform dose decisions. A clear definition matters: the toxicity categories and severity threshold determine which events count toward the endpoint. The endpoint does not encompass every adverse event, and an event listed in the safety record cannot be assumed to meet the DLT definition unless its type and grade are reported.
The registry record gives the DLT definition and assessment timeframe, but does not report a DLT count, a dose-specific DLT estimate, or the selected maximum tolerated dose. The record also does not report the result of the secondary Response Rate outcome. Consequently, the endpoint definition explains what the study intended to measure, but the posted record does not give the outcome values needed to evaluate the observed toxicity pattern or dose-finding result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record identifies a sequential Phase I/II study of topotecan with gefitinib, with dose-limiting toxicity as its primary outcome. It gives the toxicity definition, treatment schedules, enrollment, and safety-event counts. It does not report the primary DLT result, the maximum tolerated dose, a response-rate estimate, or response duration results. This means the record describes the study question and some safety reporting, but does not provide the main efficacy and dose-finding results sought in the study summary.
The serious adverse event fields list zero affected participants at each Phase 1 dose level and in the expansion phase. The corresponding at-risk counts are 3, 3, 3, and 10. Deaths are listed as zero in each group. These figures describe the registry’s serious-event reporting; they are not the primary DLT result. The record also lists other adverse events affecting 3, 3, 3, and 9 participants across those groups. Those other-event counts do not reveal event grades or whether an event met the DLT definition.
These counts should be read within the study’s sequential design. The dose levels and expansion phase are not randomized comparison groups, and the study does not list a control arm. Differences in counts across groups cannot be interpreted as causal treatment contrasts. The registry record does not describe enough about exposure duration, follow-up, or event ascertainment to make a more detailed comparison across phases or dose levels.
Precision cannot be assessed for the primary outcome because no DLT estimate or interval is reported. More generally, a point estimate describes an estimated outcome, while a confidence interval conveys the range of values compatible with the data under the method used. Without a reported estimate and confidence interval, readers cannot judge the statistical precision of a DLT or response result. No p-value or inferential analysis result is reported in the registry record.
The enrollment figure and the safety counts do not substitute for missing outcome estimates. Nor do the safety-event counts establish that no dose-limiting toxicities occurred: the safety fields do not report the grade-specific information required to map those events to the stated DLT definition. The registry record lists no serious adverse event terms. This should be distinguished from a comprehensive account of all harms, which is not available in the posted record.
Accordingly, the posted information supports a description of the trial design and the recorded adverse-event counts, but not a conclusion about the magnitude or precision of the primary endpoint or response outcomes. The absence of a reported outcome is not evidence that an outcome was absent. The registry record does not report whether any additional analyses were performed or how the results were assessed outside the posted fields.
9. Statistical Methods Explained
The record describes a sequential Phase I/II design and identifies continual reassessment as the method associated with the DLT timeframe. In general, continual reassessment methods use accumulated toxicity information to guide dose selection during dose finding. They differ from a design in which all participants are assigned to dose levels in a randomized comparison. The registry record does not report the model specification, target toxicity level, dose-assignment rules, or detailed implementation, so those features cannot be reconstructed.
What does the primary endpoint count?
The primary outcome is a count of dose-limiting toxicities using the recorded definition: any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity. The distinction between a count and a rate is important. A count reports the number of events meeting the endpoint; a rate or proportion requires a clearly defined denominator and observation window. The registry record does not report the primary DLT count or an estimate of its rate. It also does not report whether repeated events in a participant were counted separately or how the endpoint was handled at the participant level.
In general, a toxicity endpoint depends on both its clinical definition and how events are collected and classified. If event grades, timing, and attribution are not available, a reader cannot independently determine which reported adverse events meet a DLT rule. The record’s adverse-event counts therefore cannot be substituted for a DLT analysis. Details about adjudication, attribution, and handling of incomplete toxicity follow-up are not reported in the registry record.
How should the design shape interpretation?
A sequential dose-finding study has a different aim from a randomized treatment-effect study. Its early phase is intended to inform dosing through observed toxicity, while the expansion phase is described as using the maximum tolerated dose from Phase I and assessing response outcomes. The registry record does not report the selected dose, the dose assignments actually made, or the results by phase. Without these data, readers cannot assess the dose-finding process or determine how the intended Phase II schedule was implemented.
General statistical interpretation also depends on the analysis population and follow-up. For a toxicity outcome, the number of events can be affected by the duration of observation and by whether participants complete the assessment period. For response, interpretation depends on the response definition, assessment schedule, and handling of participants without an evaluable assessment. Those details are not reported in the registry record. The record also does not describe the populations included in each analysis.
What do uncertainty measures add?
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the chosen statistical method. A narrow interval indicates greater precision than a wide interval, though neither interval alone resolves limitations in study design or data collection. No primary outcome estimate, confidence interval, or p-value is reported in the registry record. Precision of the DLT and response findings therefore cannot be evaluated from the posted outcomes.
The record lists 0 analyses. This does not establish what analyses may have been conducted outside the registry record; it means that no analyses are listed there. No model results, adjusted estimates, or analysis-level uncertainty measures are reported. An unadjusted recalculation from summary statistics is not available for the primary endpoint because its summary result is not reported.
How should planning assumptions be read?
Any sample-size illustration associated with the record is a planning exercise, not observed power. The 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 set as a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is total events; for other outcomes, it is participants per arm. These assumptions do not describe the actual sequential study design, which does not list a randomized two-arm comparison. The registry record does not report the trial’s own sample-size justification, so the planning illustration should not be treated as evidence that the study had a particular probability of detecting an effect.
Over-dispersion is a general statistical issue for count data: it occurs when observed variation exceeds what a simple count model assumes, and can make standard errors too small if ignored. Whether it is relevant to a particular analysis depends on the data and model. The registry record does not report a fitted model or count-data analysis, so no conclusion about over-dispersion can be made for this study.
10. Multiplicity, Missing Data and Analysis Populations
The record lists Dose Limiting Toxicity as the primary outcome and Response Rate as a secondary outcome. The study summary also describes response duration as an aim. The record lists three outcome measures, but does not report a multiplicity strategy, such as how interpretation would account for assessing more than one outcome. It also does not report a hierarchy or adjustment procedure. Without those details and the outcome results, the impact of multiple assessments on statistical interpretation cannot be evaluated.
Missing-data methods and analysis populations are not reported in the registry record. The record does not describe how participants with incomplete toxicity observation, missing response assessments, or other unavailable measurements were handled. It also does not report whether all enrolled participants were included in each outcome analysis or whether any participants were excluded. These details matter because analysis populations and missingness can affect the interpretation of estimated outcomes.
No response-rate result, response-duration result, DLT result, or analysis-level estimate is reported. The record lists 0 analyses, but that does not establish whether analyses were conducted outside the registry record. It indicates that analysis results are not listed there. Without reported estimates, uncertainty measures, analysis populations, and missing-data procedures, readers cannot assess the robustness of the outcome findings or the statistical consequences of multiple outcomes.
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 |
|---|---|---|---|
| Phase 1 Dose Level 1 | 0 | 3 | 0.0% |
| Phase 1 Dose Level 2 | 0 | 3 | 0.0% |
| Phase 1 Dose Level 3 | 0 | 3 | 0.0% |
| Expansion Phase | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase 1 Dose Level 1 | 0 of 3 |
| Phase 1 Dose Level 2 | 0 of 3 |
| Phase 1 Dose Level 3 | 0 of 3 |
| Expansion Phase | 0 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Phase 1 Dose Level 1 | 3 of 3 |
| Phase 1 Dose Level 2 | 3 of 3 |
| Phase 1 Dose Level 3 | 3 of 3 |
| Expansion Phase | 9 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase 1 Dose Level 1 | Phase 1 Dose Level 2 | Phase 1 Dose Level 3 | Expansion Phase |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 3 of 3 | 3 of 3 | 3 of 3 | 9 of 10 |
| Fatigue | General disorders | 3 of 3 | 3 of 3 | 3 of 3 | 9 of 10 |
| Hemoglobin | Blood and lymphatic system disorders | 2 of 3 | 3 of 3 | 3 of 3 | 9 of 10 |
| Abdominal pain | Gastrointestinal disorders | 2 of 3 | 3 of 3 | 2 of 3 | 9 of 10 |
| Constipation | Gastrointestinal disorders | 3 of 3 | 2 of 3 | 1 of 3 | 9 of 10 |
| Neutrophils | Blood and lymphatic system disorders | 2 of 3 | 3 of 3 | 2 of 3 | 6 of 10 |
| Nausea | Gastrointestinal disorders | 2 of 3 | 1 of 3 | 2 of 3 | 6 of 10 |
| Acne | Skin and subcutaneous tissue disorders | 3 of 3 | 2 of 3 | 0 of 3 | 6 of 10 |
| Neuropathy | Nervous system disorders | 2 of 3 | 2 of 3 | 2 of 3 | 5 of 10 |
| Hypomagnesemia | Metabolism and nutrition disorders | 1 of 3 | 3 of 3 | 0 of 3 | 6 of 10 |
The serious adverse event fields report zero affected participants in each listed group. The at-risk counts are 3 for Phase 1 Dose Level 1, 3 for Phase 1 Dose Level 2, 3 for Phase 1 Dose Level 3, and 10 for the Expansion Phase. Deaths are reported as zero for each group. The registry record lists no serious adverse event terms.
Other adverse events are reported separately: the affected counts are 3, 3, 3, and 9 in the corresponding groups. These are not serious-event counts, and the record does not report their grades or whether they met the DLT definition. The listed groups reflect the sequential dose levels and expansion phase, not randomized comparison arms. Their counts should not be read as a comparative treatment effect.
Serious adverse event counts are not a complete account of tolerability, and the recorded zeros do not establish that no dose-limiting toxicities occurred. The registry record does not provide the event-level information or primary DLT result needed to make that determination. It also does not report further detail on event timing, exposure, or follow-up.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed Phase I/II study of weekly topotecan with daily gefitinib in patients with platinum-resistant ovarian, peritoneal, or fallopian tube cancer. It specifies the primary DLT definition, the treatment schedules, and the intended dose-finding and response questions. It also reports serious adverse event counts and other adverse-event counts for the listed dose-level and expansion groups.
The record does not report the primary DLT result, the maximum tolerated dose, or results for Response Rate and response duration. It therefore does not establish from the posted results what toxicity outcomes were observed under the endpoint definition, what dose was selected, or what response outcomes occurred. The absence of these results in the registry record should not be interpreted as a finding of no toxicity or no response.
The design is sequential and has no listed randomized comparator. As a result, the record does not provide a randomized estimate of the combination’s effect relative to another treatment or control. The reported safety counts are descriptive and cannot be interpreted as like-for-like comparisons across groups. The registry record also does not report confidence intervals, p-values, analysis populations, or methods for missing data, limiting assessment of precision and robustness.
In general, a trial result must be interpreted in light of its endpoint definition, design, outcome estimates, and uncertainty. Here, the definition and design are available, but the primary and response estimates are not. Readers can understand the question the study set out to address and some of the adverse-event reporting, but cannot use the posted record alone to quantify the study’s primary outcome or response findings.
13. Why This Trial Matters Statistically
This study illustrates why design and outcome reporting must be read together. A sequential Phase I/II study asks a dose-finding question and then describes assessment of response at the selected dose. Its logic differs from a randomized comparison intended to estimate a treatment contrast. The registry record identifies the sequential design and the primary toxicity endpoint, making clear that the reported groups should not be treated as randomized controls.
The DLT definition is also central to interpretation. The primary endpoint is not simply any adverse event; it is limited to the stated severity categories. Separate adverse-event counts cannot answer the primary question unless their event types and grades are reported in a way that permits classification under that definition. The record’s serious-event counts and other-event counts therefore offer safety context, but do not replace a DLT result.
Statistically, reporting an endpoint estimate with a measure of uncertainty is necessary to assess how precisely an outcome was measured. The registry record does not report the primary estimate or uncertainty measures, nor does it report a response result. This leaves the study’s main dose-finding and response questions unresolved in the posted results, even though the study status is completed.
The record also illustrates the importance of distinguishing design planning from observed findings. General sample-size illustrations based on equal allocation between two arms do not match the listed sequential design and should not be read as observed power. The trial’s own sample-size justification is not reported. These distinctions prevent planning assumptions from being mistaken for evidence about the precision or strength of the study’s results.
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.
Several study-specific limitations in interpreting the registry record follow from the information that is not reported. The primary DLT result and maximum tolerated dose are absent, as are the response-rate and response-duration results. Consequently, the central outcomes described in the study summary cannot be evaluated from the posted results.
The study is sequential, with no randomized comparator listed. The groups reported for Phase 1 dose levels and the expansion phase do not constitute a like-for-like control comparison. The record does not report dose assignments in sufficient detail to reconstruct the dose-finding process or determine which dose was used in Phase II.
The adverse-event information is limited to counts by group. The record does not report the grades or event details needed to identify which events met the DLT definition, and it does not list serious adverse event terms. Further information on follow-up, exposure, event ascertainment, and analysis populations is not reported in the registry record. Missing-data procedures and the handling of participants without evaluable outcomes are also not reported.
The record does not report statistical estimates, confidence intervals, p-values, or a multiplicity strategy. It does not provide the trial’s own sample-size justification or a detailed statistical analysis plan. These omissions limit assessment of precision, robustness, and the relationship between planned and conducted analyses. They do not by themselves show that the analyses were not performed; they indicate that those details and results are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Topotecan and Gefitinib (Iressa) for Ovarian, Peritoneal, or Fallopian Tube Cancer — NCT00317772.
- Registry record last updated 2022-02-07; status last verified 2022-01.
- Results first posted 2022-02-07.
- 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
NCT00317772 is a completed Phase I/II study sponsored by M.D. Anderson Cancer Center. It evaluated weekly topotecan with daily gefitinib in patients with platinum-resistant ovarian, peritoneal, or fallopian tube cancer. The listed design is sequential, with no masking and no randomized comparator. Enrollment is 19.
The primary outcome is the number of dose-limiting toxicities, defined as any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity. The record describes continual reassessment before each 28 day cycle over an average of 60 days. Response Rate is listed as a secondary outcome. The registry record does not report the primary outcome result, maximum tolerated dose, or response results.
Serious adverse event counts and deaths are listed as zero in each group; other adverse-event counts are also reported. These safety counts do not provide the missing DLT or response outcomes. The start date is 2004-09-02 and the primary completion date is 2020-11-04.