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 Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) As Maintenance Therapy in Patients With Ovarian Cancer in a Second or Third Complete Remission (NCT00739661), a randomized phase 2 study. The primary outcome is Progression-free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00739661 |
| Phase | Phase 2 |
| Condition | Ovarian Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 104 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with ovarian cancer who were in a second or third complete remission. The primary endpoint population was all randomized patients, described as the intent-to-treat population.
Intervention
Vismodegib 150 mg, taken orally once daily until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study.
Comparator
Placebo to vismodegib, taken orally once daily until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study.
Primary question
What was the time from randomization to radiographically confirmed progression or death in each randomized group? The registry record reports median progression-free survival and a 95% confidence interval for each group.
The trial addressed maintenance treatment during remission, when patients had no evidence of tumors at study entry. Its primary endpoint was progression-free survival (PFS), defined as the time between randomization and radiographic disease progression or death for any reason. The clinical question is therefore about the duration until either of those events, not about tumor response among patients with measurable disease at the start.
The registry record describes a randomized comparison between vismodegib and placebo. Randomization was stratified according to whether a patient was in a second or third complete remission. That design feature indicates that remission status was taken into account when assigning treatment; the registry record does not report a separate treatment result for either remission subgroup.
The primary results are medians with confidence intervals, not a reported estimate of the relative rate of progression or death between groups. A numerical difference between the medians alone does not establish whether the groups differed statistically. A comparative hazard ratio, its confidence interval, and a p-value are not reported in the registry record.
3. Trial Design
This was a Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial sponsored by Genentech, Inc. The registry record lists enrollment of 104 patients. Participants were randomized in a 1:1 ratio to vismodegib or placebo, with 52 patients in each arm in the posted primary outcome results. The allocation was stratified by second versus third complete remission.
Patients assigned to vismodegib received 150 mg orally once daily. Patients assigned to placebo received placebo to vismodegib orally once daily. In both groups, treatment was to continue until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study. The registry record describes the trial as double-blind, but further details about which individuals were masked and how masking was maintained are not reported in the registry record.
The study began in 2008-12, had a primary completion date of 2010-11, and is listed as completed. The primary PFS timeframe is described as running from randomization through the data cut-off date of May 15, 2010, up to 100 weeks. No further detail about the number of participating centers, recruitment procedures, or follow-up beyond that timeframe is reported in the registry record.
The primary analysis population was all randomized patients, identified as the intent-to-treat population. The primary endpoint was PFS. Two secondary outcomes are listed: PFS in patients with versus without Hedgehog antigen tumor expression, and overall survival. Results or analyses for these secondary outcomes are not reported in the registry record. The record does not describe a formal sample-size justification or a detailed 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 | Vismodegib 150 mg | Placebo to Vismodegib |
|---|---|---|
| STARTED | 52 | 52 |
| COMPLETED | 6 | 10 |
| NOT COMPLETED | 46 | 42 |
Reasons for not completing this period:
| Reason | Vismodegib 150 mg | Placebo to Vismodegib |
|---|---|---|
| Adverse Event | 2 | 0 |
| Physician decision to withdraw patient | 1 | 0 |
| Patient decision to withdraw | 9 | 4 |
| Disease progression, radiographic | 33 | 37 |
| Reason for discontinuation not available | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat patient population: All randomized patients.
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 | Vismodegib 150 mg | Placebo to Vismodegib | Total |
|---|---|---|---|---|
| Participants analysed | 52 | 52 | 104 | |
| Age, Continuous | years | 57.3 (SD 10.2) | 58.6 (SD 8.9) | 57.9 (SD 9.6) |
| Sex: Female, Male: Female | Participants | 52 | 52 | 104 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS), measured over From randomization date through the data cut-off date of May 15, 2010, up to 100 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint, progression-free survival (PFS), measures the time from randomization until radiographically confirmed disease progression or death for any reason. Patients entered the trial in complete remission and had no evidence of tumors at the start. For this population, radiographic evidence of a tumor was the stated definition of progression. Tumor assessments by computed tomography of the chest, abdomen, and pelvis were performed at screening and every 8 weeks during the study.
PFS is a time-to-event endpoint: it accounts for both whether an event occurred and how long it took to occur. In general, this kind of endpoint can describe the time patients remain alive without the defined disease event. It is useful for studying a maintenance strategy because the question concerns the duration of remission-related disease control, rather than only a single assessment of tumor size.
The registry record reports median PFS in months with a 95% confidence interval for each arm. The median is a summary of the event-time distribution, not the time every participant experienced before progression or death. The confidence interval communicates uncertainty around the estimated median. The exact method used to estimate the medians and intervals is not reported in the registry record, nor is a comparative hazard ratio or p-value.
Because death from any cause was included in the endpoint definition, PFS combines radiographic progression and death into a single outcome. The registry record does not provide separate counts or timing for these event types, so the reported median cannot identify which type of event contributed to the results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
Median PFS was 7.5 months in the vismodegib arm, with a 95% confidence interval from 5.59 to 11.24 months. In the placebo arm, median PFS was 5.8 months, with a 95% confidence interval from 4.14 to 7.49 months. These are the posted arm-specific summaries for the intent-to-treat population of all randomized patients.
The estimates describe the middle of each arm’s PFS distribution. They do not mean that every patient experienced progression or death at the median time, and they do not describe the event experience of any particular patient. The confidence intervals indicate that the median estimates are uncertain; they should be read as intervals around estimates rather than as ranges containing all individual outcomes.
The registry record does not report a sponsor-reported comparative hazard ratio, a confidence interval for a between-arm effect, or a p-value. The arm-specific medians and their confidence intervals are not a substitute for a formal comparative analysis. In particular, the confidence intervals for the two medians cannot by themselves establish whether a between-group difference is statistically significant. No comparison should be inferred solely from the apparent ordering of the two point estimates.
The listed primary endpoint timeframe runs from randomization through the data cut-off date of May 15, 2010, up to 100 weeks. The registry record does not report the number of progression events or deaths, how many observations were censored, or the distribution of follow-up time. Without those details, the precision and maturity of the time-to-event evidence cannot be fully assessed from the registry record.
The record lists two secondary outcomes but does not report their results or analyses. It also does not report a treatment-effect estimate within the Hedgehog antigen expression subgroups or an overall-survival comparison. The posted primary endpoint therefore supports a description of the two arm-specific median estimates, but not conclusions about those secondary questions or the relative treatment effect.
The study randomized 52 patients to each arm, and the endpoint population was defined as all randomized patients. This is the stated analysis population, but the registry record does not provide a participant flow description, the number included in each endpoint calculation, or details of missing observations. These omissions limit assessment of how complete the outcome data were and whether any participants were excluded from particular calculations.
9. Statistical Methods Explained
What does a median time-to-event result mean?
In general, a median time-to-event result is the point at which half of the estimated event-time distribution lies on either side. It summarizes the timing of an event across a group; it is not an average and does not imply that all participants had an event by that time. For this trial, the event was radiographic progression or death, and the reported medians were 7.5 months for vismodegib and 5.8 months for placebo.
Time-to-event methods are often used when some participants have not experienced the event by the end of observation or are no longer observed before an event is recorded. Those observations are generally described as censored. The registry record does not state how many observations were censored or specify the method used to handle them. It would therefore be inappropriate to assert a particular estimation procedure from the posted results alone.
How should the confidence intervals be read?
In general, a confidence interval expresses uncertainty about an estimated quantity under the assumptions of the statistical method used. The 95% confidence intervals reported for this trial are 5.59 to 11.24 months for vismodegib and 4.14 to 7.49 months for placebo. They are intervals for the respective arm-specific median estimates, not intervals for a treatment contrast. The registry record does not report a confidence interval for a between-arm comparison.
Intervals around separate estimates do not directly answer whether the estimates differ. A formal comparative analysis uses an effect measure and its uncertainty, such as a hazard ratio and confidence interval, or a prespecified test. Neither a comparative hazard ratio nor a p-value is reported in the registry record. The stated medians can be described as arm-specific results, but a claim about statistical evidence for a difference cannot be made from them alone.
What would a hazard ratio add?
In general, a hazard ratio compares the event rates over time between groups, subject to the assumptions of the model used to estimate it. It is not the same as a ratio of medians, and it is not a direct measure of the difference in median PFS. A hazard ratio is useful as a comparative summary when its assumptions and analysis are appropriate, but its interpretation depends on the trial design and the observed event-time patterns. The registry record lists no posted comparative hazard ratio for this endpoint. The record also does not report whether a proportional-hazards assumption was assessed or whether another model was used.
Why do time-to-event methods account for censoring?
As a general statistical concept, censoring occurs when an event time is not fully observed, for example because observation ends while a participant remains event-free. Time-to-event procedures can use the event-free follow-up that was observed without treating the participant as if an event had occurred at the last observation. This depends on suitable assumptions about censoring and complete recording of relevant follow-up. The registry record does not describe censoring rules, follow-up completeness, or sensitivity analyses, so the handling of these issues cannot be evaluated from its posted results.
What do the planning assumptions mean?
General sample-size calculations ask how much information a future or planned study might need to detect a specified effect under stated assumptions. The planning illustration associated with this trial uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. For time-to-event endpoints, the stated planning framework uses a total number of events. These are planning assumptions, not observed trial outcomes, and they are not evidence of the trial’s statistical power after completion. The registry record does not report the trial’s own sample-size justification, and numerical planning results or effect fractions are not reported in the registry record.
Over-dispersion is a general issue for count outcomes: it means that observed variability exceeds what a simple count model assumes, potentially making uncertainty estimates too narrow if the model does not account for it. PFS is a time-to-event endpoint rather than a count endpoint, and no count-model analysis is reported for the primary outcome. Nothing in the registry record indicates that over-dispersion was assessed in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three outcome measures: the primary PFS endpoint, PFS in patients with versus without Hedgehog antigen tumor expression, and overall survival. It reports two secondary outcomes, but no secondary analyses or results are posted. The registry record does not state how many statistical tests were planned, whether testing was ordered hierarchically, or whether any adjustment for multiple comparisons was planned. A multiplicity strategy is therefore not reported in the registry record.
Multiplicity matters in general because examining several outcomes or subgroups can increase the chance of finding an apparently notable result by chance. Without a stated testing plan and the secondary results, readers cannot assess how the secondary questions were analyzed or interpret any pattern across outcomes. No subgroup-specific effect estimate is reported for PFS by Hedgehog antigen tumor expression.
The primary analysis population is identified as all randomized patients, or the intent-to-treat population. That description clarifies the intended population for the posted primary endpoint, but the registry record does not report participant flow, the number with an assessable endpoint, or details of missing outcome data. The method for handling missing observations, withdrawals, or loss to follow-up is not reported in the registry record.
In general, missing-data methods can affect time-to-event estimates if follow-up ends before an event is observed or if outcome assessments are incomplete. The posted record does not describe sensitivity analyses or assumptions about missingness. It is therefore not possible to judge from the registry record how robust the primary result is to incomplete follow-up or missing assessments.
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 |
|---|---|---|---|
| Vismodegib 150 mg | 6 | 52 | 11.5% |
| Placebo to Vismodegib | 3 | 52 | 5.8% |
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 |
|---|---|
| Vismodegib 150 mg | 51 of 52 |
| Placebo to Vismodegib | 44 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | Vismodegib 150 mg | Placebo to Vismodegib |
|---|---|---|---|
| Cardiac Failure Congestive | Cardiac disorders | 1 of 52 | 0 of 52 |
| Abdominal Pain | Gastrointestinal disorders | 1 of 52 | 0 of 52 |
| Small Intestinal Obstruction | Gastrointestinal disorders | 0 of 52 | 1 of 52 |
| Chest Pain | General disorders | 1 of 52 | 0 of 52 |
| Device Related Infection | Infections and infestations | 0 of 52 | 1 of 52 |
| Urinary Tract Infection | Infections and infestations | 0 of 52 | 1 of 52 |
| Hepatic Enzyme Increased | Investigations | 1 of 52 | 0 of 52 |
| Lung Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 52 | 0 of 52 |
| Renal Colic | Renal and urinary disorders | 1 of 52 | 0 of 52 |
| Emphysema | Respiratory, thoracic and mediastinal disorders | 1 of 52 | 0 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vismodegib 150 mg | Placebo to Vismodegib |
|---|---|---|---|
| Dysgeusia | Nervous system disorders | 35 of 52 | 9 of 52 |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | 35 of 52 | 1 of 52 |
| Alopecia | Skin and subcutaneous tissue disorders | 28 of 52 | 4 of 52 |
| Fatigue | General disorders | 14 of 52 | 15 of 52 |
| Nausea | Gastrointestinal disorders | 17 of 52 | 9 of 52 |
| Abdominal Pain | Gastrointestinal disorders | 10 of 52 | 7 of 52 |
| Constipation | Gastrointestinal disorders | 12 of 52 | 5 of 52 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 8 of 52 | 8 of 52 |
| Diarrhoea | Gastrointestinal disorders | 6 of 52 | 8 of 52 |
| Vomiting | Gastrointestinal disorders | 8 of 52 | 5 of 52 |
Serious events with the highest arm-level rate: cardiac failure congestive (1.9%), abdominal pain (1.9%), small intestinal obstruction (1.9%), chest pain (1.9%), device related infection (1.9%).
The registry record reports serious adverse events affecting 6 of 52 participants in the vismodegib arm and 3 of 52 in the placebo arm. It also reports other adverse events affecting 51 of 52 participants assigned to vismodegib and 44 of 52 assigned to placebo. These are arm-specific participant counts as posted; they do not by themselves establish that treatment caused an event or that event severity was the same across participants.
The serious adverse event terms listed are cardiac failure congestive, abdominal pain, small intestinal obstruction, chest pain, device related infection, and urinary tract infection. Each term is reported as 1.9%. The registry record does not provide further detail about the timing, duration, outcome, or relationship to treatment for these listed events. The term-level percentages should not be treated as a complete description of the clinical circumstances of each event.
Death counts are not reported in the registry record. The adverse-event figures are distinct from the PFS endpoint, which includes death for any reason as one of its event types. The registry record does not provide enough information to determine which, if any, deaths were included in the primary endpoint results.
In general, adverse-event counts summarize events recorded during a trial and should be interpreted alongside definitions, follow-up, and attribution procedures. Those additional details are not reported in the registry record. The counts alone do not establish comparative safety or support an individual treatment decision.
12. What the Result Does, and Does Not, Mean
The posted results show arm-specific median PFS estimates of 7.5 months for vismodegib and 5.8 months for placebo in a randomized trial of patients with ovarian cancer in a second or third complete remission. The reported confidence intervals convey uncertainty around each median. These estimates describe the observed endpoint summaries in the registry record; they do not establish a comparative treatment effect by themselves.
The results do not show the timing of progression and death separately, the number of endpoint events, or the follow-up experience of each participant. A median is a group-level summary and cannot predict an individual participant’s outcome. The record also does not provide the comparative hazard ratio, its confidence interval, or a p-value that would ordinarily help quantify the treatment contrast.
The results do not answer the listed secondary questions. There is no posted result for PFS by Hedgehog antigen tumor expression or for overall survival. Nor does the registry record describe a multiplicity plan, missing-data procedures, or the trial’s own sample-size justification. These absences leave important aspects of the analysis and interpretation unresolved.
The safety record lists serious adverse events affecting 6 participants in the vismodegib arm and 3 in the placebo arm, as well as other adverse events affecting 51 and 44 participants, respectively. The registry record does not establish whether individual events were caused by treatment, and death counts are not reported.
In general, a randomized comparison can help evaluate differences between groups, but interpreting its evidence requires the prespecified analysis, uncertainty around the comparative effect, and information about endpoint completeness. For this record, the reported medians and safety counts are informative descriptions, but they are not enough to support a definitive conclusion about the relative effects of the study treatments.
13. Why This Trial Matters Statistically
This trial is statistically notable as a randomized, double-blind, placebo-controlled comparison in a remission population, with equal allocation and a primary endpoint defined by time to radiographic progression or death. Those features make the central statistical question a comparison of event-time distributions rather than a comparison of a single measurement at one visit. Randomization was stratified by second versus third complete remission, a design choice relevant to the population’s clinical status.
The posted primary results also illustrate the distinction between arm-specific summaries and a comparative effect. The median estimates are 7.5 months and 5.8 months, each with its own 95% confidence interval, but the registry record does not report a hazard ratio or other formal comparative estimate. Reading the medians as if they directly establish a treatment contrast would overstate what the posted statistics show.
The record is also a useful example of the role of analysis transparency. The primary population is named, and the endpoint definition and assessment schedule are described. However, the trial’s sample-size justification, detailed statistical plan, missing-data procedures, and secondary analyses are not reported in the registry record. Such information helps readers understand how outcome data were analyzed and how uncertainty was handled.
Finally, safety counts and efficacy summaries address different questions. The serious and other adverse-event counts describe recorded events in each arm, while PFS combines progression and death over time. Neither set of figures alone supplies a complete account of comparative benefit and risk. Statistical interpretation depends on keeping those outcome types and their uncertainties distinct.
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 results available in the registry record are limited to arm-specific median PFS estimates and confidence intervals. A comparative hazard ratio, comparative confidence interval, and p-value are not reported. Consequently, the magnitude and statistical uncertainty of a formal between-arm effect cannot be evaluated from the posted primary results.
Although the PFS definition and assessment schedule are described, the registry record does not report event counts, censoring information, the number of participants with complete outcome data, or the estimation method. It also does not describe follow-up completeness, missing-data handling, or sensitivity analyses. These omissions restrict assessment of the time-to-event estimates and their robustness.
The registry record lists secondary outcomes for PFS by Hedgehog antigen tumor expression and overall survival, but no results or analyses are posted. The multiplicity strategy is not reported. The trial’s own sample-size justification and detailed statistical analysis plan are also not reported in the registry record.
For safety, arm-specific counts and selected serious adverse event terms are listed, but the record does not report death counts, event attribution, timing, or detailed outcomes. The information supports a description of the posted counts, not a complete comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) As Maintenance Therapy in Patients With Ovarian Cancer in a Second or Third Complete Remission — NCT00739661.
- Registry record last updated 2017-06-08; status last verified 2017-05.
- Results first posted 2012-04-26.
- 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
NCT00739661 is a completed Phase II, multicenter, randomized, double-blind, placebo-controlled trial sponsored by Genentech, Inc. It enrolled 104 patients with ovarian cancer in a second or third complete remission, randomized in a 1:1 ratio to vismodegib 150 mg or placebo. Randomization was stratified by remission status.
The primary endpoint was PFS, defined as time from randomization to radiographically confirmed progression or death for any reason. The posted medians were 7.5 months for vismodegib and 5.8 months for placebo, with 95% confidence intervals of 5.59 to 11.24 months and 4.14 to 7.49 months, respectively. A comparative hazard ratio and p-value are not reported in the registry record.
Two secondary outcomes are listed, but their results are not reported. Serious adverse events affected 6 participants assigned to vismodegib and 3 assigned to placebo; other adverse events affected 51 and 44 participants, respectively. Death counts are not reported in the registry record.