This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase I/II Study of Ganetespib in Combination With Doxorubicin (NCT02261805), a non-randomized phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02261805 |
| Phase | Phase 1, Phase 2 |
| Condition | Cancer, Small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Georgetown University |
| Results posted | Yes |
2. Clinical Question
Population
The Phase I part enrolled patients with advanced solid tumors. The planned safety dose expansion was for people with relapsed or refractory small cell lung cancer. The record reports enrollment of 11, but does not specify how many participants were assessed in each part or the characteristics of the enrolled population.
Intervention
The treatment combined ganetespib with doxorubicin. The Phase Ib descriptions specify ganetespib at 100 mg/m2 or 150 mg/m2, given intravenously on days 1 and 8 of a 21-day cycle, with doxorubicin 50 mg/m2 intravenously on day 1 of a 21-day cycle. The Phase II expansion description uses the 150 mg/m2 ganetespib dose with the same doxorubicin schedule.
Comparator
There was no randomized control group. The registry identifies the allocation as nonrandomized and describes sequential study parts and dose levels. These treatment groups are not like-for-like controls, so the record cannot support a randomized between-group treatment comparison.
Primary question
The primary outcome was maximum tolerated dose: the ganetespib dose at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity. The study also planned a safety dose expansion to assess whether there was a signal of efficacy in relapsed or refractory small cell lung cancer, with objective response rate listed as a secondary outcome. The registry record does not report the maximum tolerated dose or an objective response result.
3. Trial Design
This was a Phase I/II, nonrandomized, unmasked study with a sequential model. The record describes a dose-finding part in patients with advanced solid tumors followed by a safety dose expansion in relapsed or refractory small cell lung cancer. The Phase I purpose was to determine the recommended Phase II dose of ganetespib when combined with doxorubicin. The Phase II expansion was intended to use that dose and assess safety and a possible efficacy signal in the specified lung cancer population.
The registry lists two Phase Ib dose levels. At Dose Level 1, ganetespib was 100 mg/m2 intravenously on days 1 and 8 of a 21-day cycle, and doxorubicin was 50 mg/m2 intravenously on day 1. At Dose Level 2, ganetespib was 150 mg/m2 on days 1 and 8, with doxorubicin on the same schedule. The Phase II Expansion description also specifies ganetespib 150 mg/m2 and doxorubicin 50 mg/m2 on those schedules. These are descriptions of the assigned regimens, not evidence that a particular dose was established as the recommended Phase II dose.
The study began in 2014-10, and the recorded primary completion date is 2016-10. Its status is terminated. The registry record does not state why the study was terminated or give a termination date. It reports enrollment of 11; it does not give the distribution of enrollment across the dose levels and study parts.
Because allocation was nonrandomized and masking was absent, the design does not provide a randomized control comparison. The sequential dose structure is suited to dose and safety assessment, but comparisons across its groups would not by themselves isolate a treatment effect. The registry record does not report a detailed allocation procedure or a statistical analysis plan.
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 | Ganetespib and Doxorubicin - Phase Ib Dose Level 1 | Ganetespib and Doxorubicin - Phase Ib Dose Level 2 | Ganetespib and Doxorubicin - Phase II Expansion |
|---|---|---|---|
| STARTED | 3 | 6 | 2 |
| COMPLETED | 3 | 6 | 2 |
| NOT COMPLETED | 0 | 0 | 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 | Ganetespib and Doxorubicin |
|---|---|---|
| Participants analysed | 11 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose, measured over 1 year.
| 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 is maximum tolerated dose, recorded in mg/m^2. The registry defines it as the dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity, with a timeframe of 1 year. This is a dose-finding endpoint: it is intended to identify a dose boundary based on observed dose-limiting toxicity in the context of the combination with doxorubicin. It is not an estimate of how much the combination changes a clinical outcome relative to a control group.
In general, dose-finding studies use this kind of endpoint to inform the dose selected for further study. Its interpretation depends on the toxicity definition, observation period, and dose-escalation procedure. The registry does not describe the detailed definition of dose-limiting toxicity or the procedure used to move between dose levels. Most importantly, it does not report the observed maximum tolerated dose or a dose-limiting toxicity result by dose level. The planned Phase II expansion and its regimen therefore should not be taken as confirmation of the primary endpoint.
Objective response rate is listed as a secondary outcome, but no response estimate is reported in the registry record. The record also does not provide an endpoint result that would establish the presence or size of an efficacy signal.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives design information and a limited set of safety counts, but it does not report a numerical result for the primary endpoint. Maximum tolerated dose is named as the primary outcome, and its definition is stated, yet the registry does not provide the dose identified, dose-limiting toxicity counts by dose level, or an analysis of the endpoint. The recommended Phase II dose is therefore not established by the result information in the record. The dose listed for the Phase II expansion is a regimen description, not a substitute for a reported dose-finding result.
Objective response rate is named as a secondary outcome. No response estimate, response count, or analysis is included in the registry record. Consequently, the record does not permit an assessment of the size or precision of a response result. The study summary says the expansion was intended to determine whether there was a signal of efficacy, but an aim is not an observed finding.
The recorded enrollment is 11. That figure alone does not show how many participants received each regimen, entered the expansion, were evaluable for the primary endpoint, or contributed to the response outcome. Those analysis-population details are not reported in the registry record. It would be inappropriate to infer the dose-specific denominators or the distribution between the study parts from the overall enrollment.
The safety record lists a combined Ganetespib and Doxorubicin group with 11 at risk for serious adverse events and 1 affected. Neutrophil count decreased is the listed top serious adverse event term, at 9.1%. The record also lists 11 at risk and 11 affected for other adverse events, and deaths of 0 in that group. These are descriptive counts, not a comparison with another treatment group. The serious adverse event figure should not be conflated with the separate all-adverse-event count.
There was no randomized comparison, and no masked assessment. The treatment groups described are parts of a sequential dose-finding and expansion design, not equivalent control arms. Any differences between dose levels or study parts could reflect their different roles and participant populations as well as treatment exposure. The record offers no comparative analysis to separate these possibilities.
The status is terminated, but the reason is not reported in the registry record. Termination alone does not establish whether it was due to safety, lack of efficacy, recruitment, or another operational reason. Without endpoint results, analysis details, and the reason for termination, the posted information supports a description of the study's design and recorded safety counts, not a conclusion about efficacy or a preferred dose.
9. Statistical Methods Explained
Statistical interpretation begins with the question a design can answer. This study was organized around sequential dose levels and a safety expansion, rather than randomized allocation to a treatment and control. Its primary question was about ganetespib dose in combination with doxorubicin. That is different from estimating a treatment effect against an untreated or alternative-treatment group. Since no randomized comparator was used, the design does not control the comparison through random assignment.
What does a maximum tolerated dose represent?
In general, a maximum tolerated dose is a dose-finding summary based on dose-limiting toxicity observations under a defined treatment and observation plan. It is not a general property of a drug independent of regimen or population: interpretation relates to the combination, dosing schedule, toxicity rules, and patients observed. In this registry, the endpoint is defined as the ganetespib dose at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity, with a timeframe of 1 year. That definition identifies the intended decision criterion, but does not itself report the observed dose or toxicity pattern.
The registry gives dose schedules for two Phase Ib levels and the expansion regimen. It does not state the full escalation algorithm, how dose-limiting toxicity was adjudicated, whether all participants completed the stated observation period, or how the dose recommendation was derived from the observed data. Those details matter because dose selection depends on how toxicity outcomes across dose levels are translated into a decision. They are not reported in the registry record, so the dose-finding process cannot be independently reconstructed from the posted information.
What can the sequential, nonrandomized structure show?
In general, a sequential design can move from dose exploration to an expansion at a selected dose, allowing a later study part to focus on safety or a signal of activity in a specified population. The record describes that intention. But participants are not randomly assigned between the listed dose levels or between the Phase I and Phase II populations. The study parts have distinct roles, and the intended populations differ. A numerical contrast between those parts would not be equivalent to a randomized treatment effect.
Open-label conduct means treatment assignment is not masked in the registry description. In general, lack of masking can influence subjective assessments, reporting, and decisions about evaluation. It does not automatically invalidate an outcome, but it is relevant when considering how measurements were collected and interpreted. The registry record does not describe outcome-assessment procedures or safeguards against assessment bias.
How should precision be considered?
In general, a confidence interval expresses the range of values compatible with data under a specified statistical method and assumptions. Narrower intervals indicate greater statistical precision, while wider intervals indicate greater uncertainty. The registry does not report a confidence interval for the primary endpoint or an objective response estimate. There is therefore no interval-based precision statement to interpret for those outcomes.
The enrollment record states 11, but enrollment is not the same as the number analyzed for every endpoint. The registry does not report endpoint-specific denominators or missing outcome counts. Without those details, the amount of information contributing to each result cannot be established. A small or incomplete observed group could make an estimate imprecise, but the available record does not allow that precision to be quantified.
What do the planning illustrations mean?
In general, a sample-size calculation describes how much information a future design might need under explicit assumptions. The planning illustrations associated with this record use 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. They are not the study's own design specification, because the registry describes a nonrandomized sequential study rather than equal allocation between randomized arms. Such illustrations should be read as hypothetical planning scenarios, not as observed power and not as evidence that the study was designed or enrolled to meet that target.
Planning calculations depend on the assumed effect, variability, allocation, outcome type, and analysis method. If the trial itself does not report the relevant effect estimate or statistical plan, the calculations cannot fill in missing trial results. They do not show that an outcome was observed, that a target was reached, or that a comparison was statistically significant.
What statistical analyses are reported?
The registry record does not provide an analysis of the primary outcome or a numerical secondary outcome result. It also does not report a p-value, confidence interval, dose-level toxicity breakdown, or an inferential comparison. No analysis method can be attributed to the investigators from the record. General statistical concepts can explain how such results might be interpreted if reported, but they cannot replace the absent estimates and methods.
For safety counts, denominators and definitions are essential. The record identifies the number at risk and affected for the listed serious and other adverse event groupings. In general, counts describe observed events in the recorded group; they do not establish a causal effect or quantify comparative risk without an appropriate comparator and clearly defined ascertainment. The reported safety figures should be interpreted as descriptive registry entries.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies maximum tolerated dose as the primary outcome and objective response rate as a secondary outcome. It does not describe a multiplicity strategy, such as whether or how interpretation would account for examining multiple outcomes, doses, or analyses. That strategy is not reported in the registry record. Without a prespecified statistical plan, it is not possible to determine which analyses were intended to be confirmatory or how any multiple testing was handled.
Missing-data methods and endpoint-specific analysis populations are also not reported. The enrollment figure does not identify how many participants contributed evaluable toxicity or response data, whether any participants lacked follow-up, or how missing outcomes were handled. The registry does not state whether analyses used all enrolled participants, treated participants, or an endpoint-specific evaluable group. These details affect the interpretation of denominators and the possibility of selection bias.
The record does not report an interim-analysis plan, sample-size justification, or detailed statistical analysis plan. The sample-size illustrations are planning scenarios under stated assumptions, not evidence of the trial's own planned enrollment or observed power. They cannot establish what analysis was planned for the sequential, nonrandomized design. Because the reason for termination is also not reported, the record does not clarify whether stopping related to a prespecified statistical rule or another consideration.
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 |
|---|---|---|---|
| Ganetespib and Doxorubicin | 1 | 11 | 9.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ganetespib and Doxorubicin | 0 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ganetespib and Doxorubicin | 11 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Ganetespib and Doxorubicin |
|---|---|---|
| Neutrophil count decreased | Immune system disorders | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ganetespib and Doxorubicin |
|---|---|---|
| Nausea | General disorders | 8 of 11 |
| Fatigue | General disorders | 6 of 11 |
| Diarrhea | Gastrointestinal disorders | 5 of 11 |
| Neutrophil count decreased | Immune system disorders | 4 of 11 |
| Constipation | Gastrointestinal disorders | 3 of 11 |
| Anemia | Blood and lymphatic system disorders | 3 of 11 |
| Anorexia | General disorders | 3 of 11 |
| Weight loss | Gastrointestinal disorders | 3 of 11 |
| Hypokalemia | Blood and lymphatic system disorders | 3 of 11 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 2 of 11 |
Serious events with the highest arm-level rate: neutrophil count decreased (9.1%).
The registry lists one combined Ganetespib and Doxorubicin group for safety. For serious adverse events, 11 were at risk and 1 was affected. The listed top serious adverse event term is neutrophil count decreased, reported at 9.1%. The registry separately lists 11 at risk and 11 affected for other adverse events, and deaths of 0. These entries describe the recorded group; they do not represent a comparison against a control group.
Serious adverse events and other adverse events are distinct registry categories. The 1 affected under the serious adverse event grouping should not be interpreted as the total number with any adverse event, because the other adverse event entry records a different grouping. The listed top term does not supply a complete event-by-event account, and the registry record does not describe the event definitions, severity grading, duration, or attribution to a study drug. Nor does it report how the safety counts were distributed by dose level or study part.
These counts are descriptive. Without a randomized comparator, they cannot establish how the observed events compare with another treatment or what would have occurred without the study combination. The record also does not describe the completeness or duration of safety follow-up beyond the primary endpoint timeframe.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a sequential, nonrandomized Phase I/II study of ganetespib with doxorubicin was conducted and is now listed as terminated. It describes the intended dose-finding question, the regimens, the planned expansion population, and selected adverse-event counts. It does not report the observed maximum tolerated dose, a dose-limiting toxicity analysis, or an objective response rate result. The central outcome questions therefore remain unanswered by the results recorded in the registry.
The planned use of ganetespib 150 mg/m2 in the expansion does not prove that this dose met the primary endpoint's dose-finding criterion. A regimen in an arm description identifies what the study part specified; it is not, by itself, a reported result or recommendation. Similarly, the statement that the expansion was intended to examine an efficacy signal describes the purpose of that study part, not evidence that a signal was observed.
The safety counts show the events recorded for the combined treatment group, including the serious adverse event count and the top serious term. They do not demonstrate a relative increase or decrease in risk, because there is no randomized control group. The registry record does not provide enough information to compare safety across dose levels or to determine which component, if any, was associated with a particular event.
In general, a nonrandomized early-phase study can help characterize dose and safety and can motivate further evaluation, but its design does not provide the same causal comparison as random allocation. Here, the registry's missing outcome results and analysis details further limit interpretation. The posted information should not be read as proof that the combination is effective or ineffective, or as a basis for choosing a dose. It documents the study's stated aims and available registry entries, while leaving the primary and secondary outcome results unreported.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary aim was dose finding rather than a randomized estimate of treatment benefit. The endpoint is defined in terms of dose-limiting toxicity at a ganetespib dose, making the decision about dose central to interpretation. A dose regimen listed for a later study part cannot replace the missing result that would show how the primary criterion was applied.
The sequential structure also illustrates why study parts should not be treated as interchangeable comparison groups. The Phase I portion concerned advanced solid tumors and dose selection; the expansion concerned relapsed or refractory small cell lung cancer and safety with an intended efficacy signal. These are distinct roles and populations. A direct contrast between them would not isolate the effect of changing dose or treatment.
The absence of a randomized comparator places limits on causal interpretation of the safety counts and any potential response results. In addition, the registry does not report the primary dose-finding result, an objective response estimate, or analysis details. This makes transparency about what is and is not in the record especially important: design intentions, regimen descriptions, and adverse-event entries are not equivalent to complete clinical outcome reporting.
Finally, the terminated status raises a question about study completion, but the reason is not reported in the registry record. Statistical interpretation cannot infer a cause from the status alone. The record therefore highlights the distinction between a trial's stated statistical question, the design used to address it, and the results needed to answer it.
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.
Important trial-specific information is absent from the registry results. The maximum tolerated dose is specified as the primary endpoint, but no observed value or dose-limiting toxicity counts by dose level are reported. The objective response rate is listed as a secondary outcome, but no response result appears. This prevents interpretation of either the central dose-finding outcome or the intended efficacy signal.
The record reports enrollment of 11 but does not identify enrollment by study part or dose level, endpoint-specific analysis populations, or evaluable denominators. It does not report participant characteristics, duration of follow-up for response, missing outcome handling, or the detailed definition and assessment of dose-limiting toxicity. These omissions limit assessment of how representative, complete, or precise the results might be.
The design was nonrandomized and unmasked, with sequential study parts that had different purposes and populations. It cannot support a randomized comparison, and the registry does not provide a statistical analysis plan or adjustment for potential bias. The reason for termination is not reported, so the status cannot be interpreted as evidence about safety, efficacy, recruitment, or any other cause.
The safety information is limited to registry group counts and a listed top serious adverse event term. The record does not provide event-level detail, dose-specific safety results, or a comparative safety analysis. Together, the missing outcome reporting and limited design detail mean that the registry record can describe study structure and selected safety entries, but cannot establish the primary dose result or efficacy findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase I/II Study of Ganetespib in Combination With Doxorubicin — NCT02261805.
- Registry record last updated 2018-04-23; status last verified 2018-03.
- Results first posted 2018-02-07.
- 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
NCT02261805 is a terminated, nonrandomized, unmasked Phase I/II study of ganetespib with doxorubicin. It used a sequential design, with dose finding in advanced solid tumors and a planned safety expansion in relapsed or refractory small cell lung cancer. The registry reports enrollment of 11 and lists regimens with ganetespib at 100 mg/m2 or 150 mg/m2 alongside doxorubicin 50 mg/m2.
The primary outcome was maximum tolerated dose, defined by dose-limiting toxicity, but the registry record does not report the result. Objective response rate is listed as a secondary outcome without a result. The safety entries list 1 affected among 11 at risk for serious adverse events, neutrophil count decreased at 9.1% as the top serious term, 11 affected among 11 at risk for other adverse events, and deaths of 0. The reason for termination and detailed statistical methods are not reported.