Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD) (NCT00862836), a na phase 1, phase 2 study. The primary outcome is Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs)..

2. Clinical Question

The study description outlines a multicentre phase I and randomized phase II program, with phase II contingent on meeting starting criteria at the end of phase I. However, the registry also classifies the design as single-group and records allocation as not applicable. The actual registered record should therefore not be read as evidence of a randomized comparison. Its secondary outcomes name progression-free survival and overall survival, but no outcome analyses are posted. The available information supports a description of the study question and the registry’s safety reporting, not a conclusion about comparative benefit or harm.

3. Trial Design

The official title describes a multicentre phase I/randomized phase II study of vandetanib added to standard therapy, pegliposomal doxorubicin, in recurrent ovarian cancer. The brief study description presents a plan for 70 patients: 10 in phase I and 60 in phase II. It states that phase II would proceed only if starting criteria were met at the end of phase I. These are planned features in the study description; they do not establish which phases were completed.

Other registry fields characterize the study as phase I and phase II, with no masking and a single-group model. Allocation is recorded as not applicable. The listed enrollment is 15, and the status is terminated. The difference between the described plan and the listed enrollment is important when interpreting the record: the planned sample does not describe the enrolled group, and the registry does not report why the study was terminated or whether phase II began.

One treatment group is listed: vandetanib 100 mg added to standard PLD therapy. There is no separately listed PLD-only group. Although the brief description calls the planned phase II randomized, the registry’s design information does not document a randomized allocation or a control arm for the registered record. The study therefore cannot be interpreted as a randomized treatment comparison on the basis of these entries.

The record lists a start date of 2009-04 and primary completion of 2010-09. It identifies Genzyme, a Sanofi Company, as sponsor. Details such as the reason for termination, the number completing follow-up, and the number assessed in each study phase are not reported in the registry record. Those omissions limit reconstruction of the trial’s conduct and participant flow.

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.

Before assignment: Phase I of the trial consisted of a safety run-in phase of 10 patients with histologically confirmed, epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory or partially sensitive to platinum-based therapy evaluable for at least 2 cycles. Phase II of the trial was not conducted.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs)., measured over From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months..

The primary endpoint is the number of participants in the safety set with at least one adverse event of grade 3 or higher. The record defines CTCAE grade 3 as severe, grade 4 as life threatening or disabling, and grade 5 as death, according to National Cancer Institute CTCAE Version 3. The stated observation period runs from registration, when the informed consent form was completed, to the last visit, up to 18 months.

A participant-level count of people experiencing at least one event is a way to summarize how often serious or severe toxicity affected participants, rather than how many separate events occurred. General statistical context: this kind of endpoint is useful for describing safety because it applies a defined severity threshold and avoids counting one participant repeatedly solely because they experienced multiple qualifying events. It does not, by itself, identify the cause of an event or establish that a treatment caused it.

The registry record does not post the primary endpoint count. The serious-adverse-event entries are not a substitute for that endpoint: seriousness and CTCAE severity are different classifications, and the record does not state that the reported serious-event counts are the number with at least one grade 3 or higher event. Consequently, the primary safety endpoint cannot be quantified from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes two phases, but its design fields identify a single-group model and allocation as not applicable. This distinction matters. A study can describe a randomized phase as part of its intended program without the registry record documenting that randomized comparison as the design actually represented. Here, the listed group is vandetanib added to PLD, with no concurrent control arm listed. Statistical conclusions should follow the registered group structure, not assume a comparison that is not documented.

What does the primary endpoint count?

The primary endpoint is a binary participant-level outcome: whether a participant experienced at least one adverse event of CTCAE grade 3 or higher during the stated observation period. The endpoint description sets the severity threshold and identifies the safety set as the population for evaluation. A participant who has one qualifying event and a participant who has more than one qualifying event each contribute to the count of participants with an event. General statistical context: binary outcomes are often summarized by counts and proportions, while uncertainty can be described with an interval estimate. The registry record does not post the primary count or an interval estimate.

The safety table lists 14 participants at risk for serious events and reports 3 affected. It also lists 14 at risk for other events and 14 affected. These entries describe the safety reporting categories in the registry; they do not supply the missing result for the primary endpoint. Seriousness of an event and its CTCAE grade are related but distinct classifications. Without a cross-tabulation or explicit mapping, the serious-event count cannot be converted into the primary grade-based count.

What can be inferred from a single group?

A single-group description can show what was recorded among participants receiving the listed regimen. It cannot separate treatment effects from the natural course of illness, background risk, participant selection, or other care. General statistical context: a concurrent control group helps estimate what might have occurred over the same period without the intervention, subject to the design and analysis assumptions. Since no control group is listed, an unadjusted comparison with an external population would introduce assumptions not documented in the registry record.

The same limitation applies to survival outcomes. Progression-free survival and overall survival are named as secondary outcomes, and the description refers to assessment in an intention-to-treat set. However, no analyses are posted, and the registry record does not provide event counts, follow-up summaries, estimates, or uncertainty intervals. No survival result can be reconstructed from the outcome titles alone.

What do significance levels and planning calculations mean?

The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is based on a fraction of the observed effect. For time-to-event outcomes, the described calculation concerns the total number of events; for other outcomes, it concerns participants per arm. These are planning assumptions, not evidence that the trial used those methods or had that allocation. They do not establish the original protocol’s sample-size rationale, which is not reported in the registry record.

General statistical context: a significance level is a rule for controlling the chance of a false positive under a specified testing framework; it does not measure the probability that a result is true. A planning sample size is an illustration of what might be needed under its assumptions. It is not observed power, and it does not show what the study could reliably detect unless the assumptions and actual design match. The registry record does not report a statistical analysis plan or a sample-size justification for the trial itself.

How should event percentages be read?

The registry lists six serious-event terms, each reported at 7.1%. These percentages are descriptive entries, and the record does not give the count for each term or clarify whether a participant could contribute to more than one term. General statistical context: when participants can experience multiple event types, percentages for separate terms should not be added to estimate the proportion with any event. Doing so could count the same participant more than once. The entries also do not, without a comparator, estimate an excess risk attributable to the regimen.

Precision depends on the amount and pattern of observed information. General statistical context: small groups usually yield less precise estimates, and confidence intervals can be wide even when a point estimate appears clear. No interval estimates are reported for the posted adverse-event entries. The enrollment listed in the registry is 15, while the safety entries show 14 at risk; the record does not explain the difference or provide a participant-flow account.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Vandetanib 100 mg")
n      <- c(14)
events <- c(9)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Vandetanib 100 mg  14  9  64.3  35.1  87.2  38.8  83.7  38.4  83.7

11. Multiplicity, Missing Data and Analysis Populations

The record lists eight outcome measures and names progression-free survival and overall survival as secondary outcomes. It does not report a multiplicity strategy, such as whether tests were ordered in a hierarchy or adjusted to account for examining multiple outcomes. This information is not reported in the registry record. General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently positive result can increase unless the analysis plan addresses multiplicity. No posted analysis results are available to assess how this issue was handled.

The primary endpoint specifies the safety set, while the secondary-outcome descriptions refer to an intention-to-treat set. These labels indicate different analysis populations, but their operational definitions are not reported in the registry record. The record does not provide participant flow, the number included in each analysis set, or reasons participants may have been excluded from an analysis.

Missing-data methods are not reported in the registry record. There is no description of how incomplete safety assessments, missing survival follow-up, or other unavailable outcome information were handled. The record also does not state whether analyses were adjusted for baseline characteristics or whether any interim analyses were conducted. No statistical analysis plan is reported. These omissions mean that analytic choices affecting estimates and uncertainty cannot be evaluated from the registry entries.

Because no outcome analyses are posted, the record does not provide the results needed to evaluate missingness, multiplicity, or consistency across analysis populations. The absence of those details should be treated as an information gap, not as evidence that a particular method was or was not used.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: arrhythmia (7.1%), abdominal pain (7.1%), ascites (7.1%), ileus (7.1%), nausea (7.1%).

The safety entry lists a Vandetanib 100 mg group, with 14 participants at risk for serious adverse events and 3 participants affected. For other adverse events, it lists 14 at risk and 14 affected. These counts are descriptive of the registry’s safety categories. The serious-event count does not equal the primary endpoint result by definition, because the primary endpoint is based on CTCAE grade 3 or higher, while serious-event classification is a separate measure.

The registry lists arrhythmia, abdominal pain, ascites, ileus, nausea, and vomiting as serious-event terms, each reported at 7.1%. The record does not state the count associated with each term, the event-level details, or whether individual participants experienced more than one listed term. The percentages should not be summed to derive a total. The record does not report deaths in the safety entry.

These entries do not establish that the regimen caused the events. There is no concurrent control group listed for comparison, and the record does not provide attribution details or uncertainty intervals. The separate primary endpoint count of participants with at least one grade 3 or higher event is not reported in the registry record.

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

The registry record documents a study of vandetanib added to standard PLD therapy and provides limited safety information for the listed Vandetanib 100 mg group. It records 3 participants with serious adverse events among 14 at risk and lists six serious-event terms, each at 7.1%. It also reports 14 participants with other adverse events among 14 at risk. These are descriptive observations, not evidence from a controlled comparison.

The central stated endpoint is the number of participants with at least one adverse event of grade 3 or higher in the safety set. That result is not reported. The separate serious-event count does not answer the endpoint question because serious-event status and CTCAE grade are not interchangeable. The record also does not post analyses for progression-free survival or overall survival, so it does not provide a basis for interpreting efficacy outcomes.

The study description anticipated a phase I/phase II program and a planned total of 70 patients, but the registry lists enrollment of 15 and terminated status. It does not explain the termination or report whether phase II proceeded. The design fields list a single group and no allocation, so the record does not document a randomized comparison, despite the planned randomized phase II described in the summary.

General statistical context: an uncontrolled group can describe observed events but cannot distinguish effects of treatment from other explanations. In addition, estimates without uncertainty measures can be difficult to interpret for precision. No confidence intervals or analysis results are posted for the stated endpoints. The record therefore cannot establish comparative safety or efficacy, and missing results should not be interpreted as proof that an effect was absent.

The most defensible reading is that the registry captures a terminated study with a defined safety endpoint and some adverse-event reporting, but an incomplete account of outcomes and analysis. It does not determine whether adding vandetanib changes clinical outcomes relative to standard therapy alone.

14. Why This Trial Matters Statistically

This record illustrates why the distinction between a planned study and the registered design information matters. The summary describes a phase I program followed by a randomized phase II if starting criteria were met. The design fields, however, list a single group and allocation as not applicable. Readers need to distinguish the proposed program from the comparison actually documented in the record; otherwise, descriptive safety data could be mistaken for randomized evidence.

It also shows why endpoint definitions must be kept separate. The primary endpoint counts participants with at least one CTCAE grade 3 or higher event, whereas the safety entry separately reports serious adverse events and other adverse events. Without the primary count or a mapping between classifications, one category cannot be substituted for another. Clear definitions are essential to interpreting safety summaries.

The record also demonstrates the importance of complete outcome reporting. Progression-free survival and overall survival are named, but no analyses are posted. The enrollment is 15, compared with a planned 70 in the study description, and the status is terminated; the reason and participant flow are not reported. These gaps constrain both statistical interpretation and assessment of how the planned design was implemented.

General statistical context: readers need estimates, uncertainty, analysis populations, and information on missing data to judge how stable and complete a result is. In this case, the registry offers some event descriptions but not the primary endpoint result or inferential analyses. Statistical significance, precision, and comparative effects cannot be assessed without those results. The record is therefore instructive as an example of how registry design fields, planned features, endpoint definitions, and posted results must be read together without assuming they answer the same question.

15. 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 registry design fields identify a single group, while the study summary describes a randomized phase II that was conditional on phase I criteria. The record does not clarify whether phase II began or whether randomization occurred. As a result, it does not document a like-for-like control comparison. The planned total of 70 patients differs from the listed enrollment of 15, and the reason for termination is not reported in the registry record.

The primary safety endpoint is defined but its count is absent. The separate safety entries report serious and other adverse events, but do not provide a cross-reference to CTCAE grade. Term-level counts, event details, attribution, and confidence intervals are not reported. Deaths are not reported in the safety entry. These gaps limit interpretation of both the frequency and precision of adverse-event outcomes.

Although progression-free survival and overall survival are named as secondary outcomes, no analyses are posted. The registry record does not report participant flow, completion of follow-up, definitions of the safety and intention-to-treat sets, missing-data handling, multiplicity methods, or the statistical analysis plan. It also does not report the trial’s sample-size justification or whether interim analyses were conducted. Consequently, readers cannot assess how closely the analysis followed the planned program or how missing information may have affected results.

The registry lists ovarian cancer as the condition and describes eligibility in terms of platinum-refractory recurrent epithelial cancer of the ovary, fallopian tube, or peritoneum. Further information about enrolled participants is not reported. These limitations mean that the posted safety entries should be interpreted narrowly as registry descriptions, not as a complete estimate of treatment-associated risk or a comparison with standard therapy alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD) — NCT00862836.
• Registry record last updated 2016-10-10; status last verified 2016-08.
• Results first posted 2012-10-11.
• 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.

19. Record Summary

The registry describes a multicentre phase I/randomized phase II study of vandetanib added to pegliposomal doxorubicin for recurrent ovarian cancer. The brief description outlines a plan for 70 patients, conditional progression to phase II, and a randomized phase II; the registry design fields instead list a single group and allocation as not applicable. Enrollment is recorded as 15, and status is terminated.

The primary endpoint is the number of participants in the safety set with at least one CTCAE grade 3 or higher adverse event, but its result is not reported. Safety reporting lists 3 participants with serious adverse events among 14 at risk and 14 with other adverse events among 14 at risk. Progression-free survival and overall survival are named as secondary outcomes, but no analyses are posted. The registry record does not report the reason for termination, participant flow, or the statistical analysis plan.