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 Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary (NCT00873119), a randomized phase 2 study. The primary outcome is Progression Free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00873119 |
| Phase | Phase 2 |
| Condition | Carcinoma of Unknown Primary |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 89 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Valerio Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Adults with previously untreated carcinoma of unknown primary were the intended population. The primary outcome description specifies an intent-to-treat population comprising all patients randomized to either treatment group. The registry record does not provide further eligibility details in the information reported for this trial.
Intervention
Arm A received belinostat in combination with carboplatin and paclitaxel. The recorded schedule describes belinostat 1000 mg/m² by intravenous infusion on days 1, 2 and 3, followed by 2000 mg orally on days 4 and 5, every 3 weeks. The description also identifies the combination with carboplatin and paclitaxel, but the full dosing details for those drugs in Arm A are not reported in the registry record.
Comparator
Arm B received carboplatin and paclitaxel. The recorded regimen specifies paclitaxel 175 mg/m² by intravenous infusion, followed by carboplatin (AUC 6) by intravenous infusion on day 1 of a 3-week cycle.
Primary question
The primary question was whether the recorded progression-free survival differed between the randomized treatment groups. Progression-free survival was defined as time from randomization to disease progression or death from any cause, with progression assessed using RECIST criteria. The registry reports median estimates and 95% confidence intervals for both arms, but does not report a hazard ratio or a sponsor-reported statistical comparison for this endpoint.
3. Trial Design
This was an open-label, randomized, parallel-group phase II trial comparing belinostat combined with carboplatin and paclitaxel (BelCaP) against carboplatin and paclitaxel (CaP) in previously untreated carcinoma of unknown primary. The registry identifies Valerio Therapeutics as the sponsor and lists the study as completed. The recorded study dates are a start in 2009-02 and primary completion in 2012-12. Enrollment is recorded as 89.
Randomization assigned participants to one of the two treatment groups. The study was open-label, with no masking recorded. That design means treatment assignment was not concealed from participants or the clinical team as described by the registry. The registry does not report details of the randomization sequence, allocation concealment, stratification factors, or procedures used to reduce bias in assessment.
The BelCaP arm included belinostat alongside carboplatin and paclitaxel. Its recorded belinostat schedule was intravenous administration on days 1, 2 and 3, followed by oral administration on days 4 and 5, with treatment described as every 3 weeks. The CaP arm received paclitaxel followed by carboplatin on day 1 of a 3-week cycle. The recorded Arm A description does not give the complete doses and administration details for carboplatin and paclitaxel, so those details should not be inferred from the comparator regimen.
The primary endpoint was progression-free survival. Best overall response, overall survival, time to response, duration of response and time to progression are also named as secondary outcomes. Results are posted for best overall response, while measures for the other named secondary outcomes are not reported in the registry record. The record does not report a formal sample-size justification or a full 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 | Arm A - BelCaP | Arm B - CaP |
|---|---|---|
| STARTED | 44 | 45 |
| COMPLETED | 0 | 19 |
| NOT COMPLETED | 44 | 26 |
Reasons for not completing this period:
| Reason | Arm A - BelCaP | Arm B - CaP |
|---|---|---|
| Patient request | 4 | 2 |
| Adverse Event | 8 | 0 |
| Progressive disease | 26 | 18 |
| Death | 2 | 1 |
| Other | 2 | 5 |
| Not treated | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population: All patients randomized to one of the two treatment groups were included in the ITT population, 12 patients (5 in Arm A and 7 in Arm B) were censored due to lack of efficacy
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 | Arm A - BelCaP | Arm B - CaP | Total |
|---|---|---|---|---|
| Participants analysed | 44 | 45 | 89 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 29 | 31 | 60 |
| Age, Categorical: >=65 years | Participants | 15 | 14 | 29 |
| Sex: Female, Male: Female | Participants | 24 | 23 | 47 |
| Sex: Female, Male: Male | Participants | 20 | 22 | 42 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival, measured over Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time from randomization until disease progression or death from any cause. In this trial, progression was assessed using RECIST criteria. The registry describes tumor assessments during treatment and continued follow-up assessments on a changing schedule, extending until 5 years from the start of study.
This time-to-event endpoint is useful when the research question concerns how long participants remain alive without documented progression. It incorporates both progression and death, rather than treating progression alone as the event. A median provides a summary of the time-to-event distribution: it identifies the point at which the estimated proportion without an event reaches one half. It is not an average duration, and it does not describe every participant’s experience.
The registry reports a median of 5.4 months for Arm A, with a 95% confidence interval from 3.0 to 6.0 months. For Arm B, it reports a median of 5.3 months, with a 95% confidence interval from 2.8 to 6.7 months. These intervals express uncertainty around each arm’s median estimate. They do not, by themselves, provide a formal estimate of the difference between the groups. A hazard ratio, confidence interval for a between-group effect, or sponsor-reported test for the primary endpoint is not reported in the registry record.
The endpoint description says that 12 patients were censored due to lack of efficacy, with 5 in Arm A and 7 in Arm B. Censoring means that the event time is not observed for a participant over the full period of interest; the participant contributes information up to the time they were last observed in the relevant analysis. How censoring was handled in the sponsor’s analysis is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results give closely placed median progression-free survival estimates: 5.4 months in the BelCaP arm and 5.3 months in the CaP arm. The confidence intervals are broad and overlap: 3.0 to 6.0 months for BelCaP and 2.8 to 6.7 months for CaP. These arm-specific summaries show the estimated median time without progression or death in each group, but do not establish the size or precision of a treatment contrast.
A difference between the medians should not be treated as the complete comparison of time-to-event outcomes. The median uses one point on the survival distribution. It does not describe the shape of the curves, the timing of events across follow-up, or whether relative differences vary over time. A direct comparison would generally be expressed through a suitable between-group time-to-event estimate, such as a hazard ratio with a confidence interval, and an associated analysis. Such sponsor-reported primary comparison results are not reported in the registry record. The posted arm medians therefore support a descriptive reading, not a firm claim that the groups were equivalent or that one was superior.
The registry also posts best overall response results. The displayed response estimates are 43.2% for Arm A and 22.2% for Arm B. The unadjusted risk difference is -0.201 for the comparison of Arm B with Arm A, with a 95% confidence interval from -0.396 to -0.007 and an unadjusted p value of 0.046. On this difference scale, the negative estimate indicates a lower response proportion in Arm B than Arm A as the comparison is coded. This is a secondary outcome and an unadjusted comparison; it should not be treated as proof of a primary progression-free survival effect or as a definitive treatment conclusion.
The response comparison is imprecise. Its confidence interval lies close to zero at one end and extends to a larger negative difference at the other, so the compatible effect sizes range from relatively small to more substantial differences on this scale. The p value describes the compatibility of the observed data with a null difference under the test’s assumptions; it does not measure the probability that the null hypothesis is true, nor the importance of the observed difference.
The two outcome types answer related but distinct questions. Best overall response describes tumor response, while progression-free survival incorporates time to progression or death. A response result may help characterize tumor activity, but it cannot substitute for the time-to-event endpoint. The record does not provide enough primary comparison information to connect the secondary response result to a sponsor-reported progression-free survival effect.
9. Statistical Methods Explained
Progression-free survival is a time-to-event outcome. Each participant’s follow-up begins at randomization, and the event is the first recorded disease progression or death from any cause. Participants who have not had a recorded event by the end of their available follow-up may be censored. Censored observations are not treated as though an event occurred at the censoring time; they contribute information up to that point. The registry reports that 12 patients were censored due to lack of efficacy, including 5 in Arm A and 7 in Arm B. The record does not give further details about the handling of censoring or the time-to-event estimation method.
What does a median time-to-event estimate represent?
A median time-to-event estimate is the time at which the estimated event-free proportion reaches one half. Here, the event-free state means alive without documented disease progression. The posted medians are 5.4 months for Arm A and 5.3 months for Arm B. These are descriptive summaries of the estimated distributions, not average times and not direct estimates of the treatment effect. A median alone leaves out information about the distribution before and after that point.
The 95% confidence interval describes statistical uncertainty around an estimate under the method used to construct it. In repeated use of the same procedure under its assumptions, intervals would cover the underlying quantity at the stated rate. It is not a range containing a specified proportion of individual participant outcomes, and it is not a probability statement about the fixed trial result. The intervals reported for the arm medians are 3.0 to 6.0 months and 2.8 to 6.7 months. The registry does not report a confidence interval for a primary between-arm effect.
Why is a hazard ratio not interchangeable with a median difference?
A hazard ratio compares event rates over follow-up, subject to the assumptions of the model used to estimate it. It uses information about event timing across the observed period, whereas a median summarizes the distribution at a single threshold. A hazard ratio is therefore not obtained by subtracting or dividing the two medians. The registry record does not report a sponsor-reported hazard ratio for progression-free survival, and the available median estimates should not be used to invent one.
Time-to-event comparisons also depend on the pattern of censoring and on how the analysis handles it. Censoring can be informative if the chance of leaving observation is related to a participant’s future outcome, and the registry does not report whether this possibility was assessed. It also does not report the specific primary analysis model, the test used for a treatment comparison, or an assumption about proportional hazards. These omissions limit independent interpretation of the primary endpoint.
How should the response comparison be read?
Best overall response is recorded as a percentage of participants. The registry posts 43.2% for Arm A and 22.2% for Arm B. For the unadjusted comparison of Arm B with Arm A, the risk difference is -0.201, with a 95% confidence interval from -0.396 to -0.007 and an unadjusted p value of 0.046. A risk difference expresses an absolute contrast in response proportions on the scale used by the analysis. The negative sign reflects the direction of the coded comparison, with Arm B compared against Arm A.
The confidence interval for a risk difference describes uncertainty in the contrast, not in either arm’s estimate alone. Because its limits are near zero at one end and extend farther from zero at the other, the estimate should be read with attention to its precision, rather than only to whether a conventional threshold is crossed. The p value is unadjusted: it does not account for examining multiple outcomes or analyses. The registry lists other secondary outcomes but does not report their results in the record.
General statistical interpretation: an unadjusted p value evaluates a comparison under the specified test and its assumptions. It is not a measure of clinical importance, and it does not indicate the probability that the treatment effect is real. The record does not report an adjusted secondary analysis or a prespecified multiplicity procedure, so the response result should be treated as exploratory rather than as a stand-alone confirmatory finding.
What does the planning illustration mean?
The sample-size illustration is based on the observed response effect, not on the trial’s original design assumptions. It describes participants per arm for 80% or 90% power under a two-sided significance level of 0.05, equal allocation, and a normal approximation, using stated fractions of the observed effect. These figures are planning illustrations for a hypothetical study, not evidence about the power achieved in this trial and not observed outcomes. They should not be confused with a reported protocol sample-size justification, which is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint is progression-free survival, and several secondary outcomes are named. Considering multiple outcomes creates a multiplicity issue: the more statistical comparisons examined, the greater the chance that at least one result may appear noteworthy by chance alone. This does not make a secondary result uninformative, but it changes how much weight an unadjusted result should carry. The registry record does not report a multiplicity adjustment, a testing hierarchy, or other prespecified procedure for controlling the interpretation of multiple comparisons.
The best overall response comparison is described as unadjusted, with a p value of 0.046. Its interpretation should therefore remain exploratory in the context of the other named secondary outcomes. The record does not report the statistical analyses for overall survival, time to response, duration of response, or time to progression, so the relationship between those outcomes and the response result cannot be assessed from the registry record.
The primary endpoint description identifies an intent-to-treat population as all patients randomized to either group and notes censoring for 12 patients due to lack of efficacy. The outcome results list 39 participants for Arm A and 38 for Arm B. Response results use denominators of 42 and 44. Serious adverse event summaries also use group denominators of 42 and 44. These differing denominators are reported for different outcomes; the registry record does not explain the relationship among these analysis sets or give a full accounting of exclusions and missing observations. The enrollment entry is 89, but the record does not reconcile that entry with the outcome-specific counts.
For a time-to-event endpoint, censoring is part of the analysis rather than equivalent to observing an event. Its implications depend on follow-up and censoring assumptions. The record gives the censoring counts and reason but does not report detailed follow-up completeness or sensitivity analyses. It also does not report the full statistical analysis plan, interim analyses, or a formal sample-size justification. These items should be described as unreported, not inferred from the endpoint results or planning illustration.
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 |
|---|---|---|---|
| Arm A - BelCaP | 22 | 42 | 52.4% |
| Arm B - CaP | 10 | 44 | 22.7% |
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 |
|---|---|
| Arm A - BelCaP | 42 of 42 |
| Arm B - CaP | 43 of 44 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A - BelCaP | Arm B - CaP |
|---|---|---|---|
| Vomiting | Gastrointestinal disorders | 4 of 42 | 0 of 44 |
| Drug hypersensitivity | Immune system disorders | 2 of 42 | 2 of 44 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 3 of 42 | 0 of 44 |
| Abdominal pain | Gastrointestinal disorders | 1 of 42 | 1 of 44 |
| Hypersensitivity | Immune system disorders | 1 of 42 | 1 of 44 |
| Dehydration | Metabolism and nutrition disorders | 2 of 42 | 0 of 44 |
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | 1 of 42 | 0 of 44 |
| Cardiac arrest | Cardiac disorders | 1 of 42 | 0 of 44 |
| Visual impairment | Eye disorders | 1 of 42 | 0 of 44 |
| Nausea | Gastrointestinal disorders | 1 of 42 | 0 of 44 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A - BelCaP | Arm B - CaP |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 36 of 42 | 26 of 44 |
| Fatigue | General disorders | 27 of 42 | 29 of 44 |
| Alopecia | Skin and subcutaneous tissue disorders | 22 of 42 | 27 of 44 |
| Diarrhoea | Gastrointestinal disorders | 24 of 42 | 17 of 44 |
| Vomiting | Gastrointestinal disorders | 26 of 42 | 13 of 44 |
| Constipation | Gastrointestinal disorders | 19 of 42 | 18 of 44 |
| Decreased appetite | Metabolism and nutrition disorders | 20 of 42 | 16 of 44 |
| Anaemia | Blood and lymphatic system disorders | 17 of 42 | 7 of 44 |
| Neuropathy peripheral | Nervous system disorders | 15 of 42 | 8 of 44 |
| Thrombocytopenia | Blood and lymphatic system disorders | 13 of 42 | 10 of 44 |
Serious events with the highest arm-level rate: vomiting (9.5%), pulmonary embolism (7.1%), drug hypersensitivity (4.8%), dehydration (4.8%), febrile bone marrow aplasia (2.4%).
The serious adverse event summaries report 22 affected participants among 42 at risk in Arm A and 10 among 44 at risk in Arm B. These are group-level counts and denominators for participants with serious adverse events; they do not describe the timing, duration, severity distribution, or causal attribution of each event. The registry also reports other adverse events affecting 42 among 42 in Arm A and 43 among 44 in Arm B. The record does not provide a comparison test for these safety summaries.
The serious adverse event terms listed include vomiting, pulmonary embolism, drug hypersensitivity, dehydration, febrile bone marrow aplasia and cardiac arrest, with percentages of 9.5%, 7.1%, 4.8%, 4.8%, 2.4% and 2.4%, respectively. Those terms and percentages should be read as reported; the registry record does not provide further detail in this summary about event duration, recurrence, seriousness criteria, or attribution to treatment. The listed percentages do not establish that an event was caused by a study drug.
Safety counts are not directly comparable to the primary efficacy endpoint. The efficacy and safety summaries use different denominators, and the record does not explain the full reasons for those differences. Death counts in the adverse event summary are not reported in the registry record. These data describe reported events; they are not a complete basis for judging the overall benefit-risk balance.
12. What the Result Does, and Does Not, Mean
The primary result describes the estimated median progression-free survival in each randomized arm. The medians are close, and each has a confidence interval expressing uncertainty. The registry does not report a sponsor-reported hazard ratio or formal primary comparison, so the posted medians do not establish whether the treatments differ on the time-to-event endpoint. Nor do they establish equivalence: a lack of a reported comparison is not evidence that the treatments have identical effects.
The secondary response result provides an unadjusted comparison and should be interpreted with caution because it is one of several named secondary outcomes and no multiplicity procedure is reported. Its estimate is uncertain, and the outcome does not answer the same question as progression-free survival. The other named secondary outcomes do not have results reported in the registry record, limiting the ability to look for coherence across endpoints.
Randomization is intended to support a fair comparison between assigned groups, but the strength of an interpretation also depends on the conduct and analysis of the study. The record identifies the design as randomized and open-label, while detailed information about allocation procedures, analysis models, missing data handling, and the statistical plan is not reported. Open-label conduct can matter for outcomes that involve clinical assessment or decisions; the registry identifies RECIST criteria for progression, but does not describe additional safeguards or blinded review.
These results should therefore be read as a registry account of outcomes, rather than as a complete statistical report. The primary endpoint is summarized by arm, but the direct treatment-effect estimate and its uncertainty are absent. The available secondary and safety data add descriptive context but do not fill that gap. No treatment recommendation or conclusion about individual care follows from these registry summaries.
13. Why This Trial Matters Statistically
This trial illustrates why an arm-specific median is not the same as a treatment comparison. The registry reports a median progression-free survival for each group and a confidence interval around each estimate, but does not report the primary between-group effect. Readers may be tempted to compare the two medians directly; that approach misses event timing across follow-up and does not provide the uncertainty of a treatment contrast.
It also demonstrates the importance of keeping endpoint types distinct. Best overall response is a binary outcome summarized as a percentage, while progression-free survival is a time-to-event outcome. Their analyses answer different questions and may use different participant sets. A response comparison cannot replace a missing hazard ratio or other formal comparison for the primary endpoint.
The record gives a useful opportunity to distinguish an unadjusted secondary result from confirmatory evidence. An unadjusted p value does not account for the set of outcomes examined, and the registry does not describe a multiplicity strategy. Planning illustrations based on the observed response effect likewise do not describe the original study design or demonstrate the power achieved. The registry’s sample-size assumptions explicitly describe a planning illustration, not a trial design justification.
Finally, outcome-specific denominators, censoring information, and incomplete reporting matter. The primary endpoint, response and safety summaries use different counts, while the record does not reconcile the analysis sets. Careful statistical reading means keeping each result attached to its outcome and denominator, recognizing what the posted analysis does not report, and avoiding conclusions that require unavailable information.
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 trial-specific limitations affect interpretation of the registry results. The primary outcome is reported as separate arm medians with confidence intervals, but a sponsor-reported between-group estimate, such as a hazard ratio, is not reported in the registry record. The primary comparison’s test, analysis model, and assumptions are also not reported. Consequently, the precision and direction of a direct treatment effect cannot be assessed from the posted primary result.
The primary endpoint description reports censoring due to lack of efficacy, but does not explain the censoring process in further detail or provide sensitivity analyses. The outcome counts differ across the primary endpoint, response and safety summaries. The record does not reconcile those counts, describe all analysis populations, or give a complete account of missing observations. The enrollment entry is 89, while the outcome-specific groups have their own reported denominators; these should not be combined or assumed to represent identical analysis sets.
The study was open-label. The registry identifies RECIST criteria for progression, but does not report whether outcome assessment was independently reviewed or otherwise protected from knowledge of treatment assignment. The detailed randomization procedure and allocation concealment are also not reported. These omissions limit assessment of potential measurement and selection biases.
Only best overall response has posted secondary results among the named secondary outcomes in the record. A multiplicity procedure is not reported, and the available response comparison is unadjusted. The registry also does not report the complete statistical analysis plan, formal sample-size justification, or interim analysis procedures. The BelCaP regimen description does not give complete dosing details for all combination drugs. These gaps mean that the results can be described, but important aspects of trial conduct and analysis cannot be independently evaluated from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary — NCT00873119.
- Registry record last updated 2015-07-28; status last verified 2015-07.
- Results first posted 2014-12-09.
- 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
NCT00873119 is a completed, randomized, open-label, parallel-group phase II trial sponsored by Valerio Therapeutics. It compared belinostat with carboplatin and paclitaxel against carboplatin and paclitaxel in previously untreated carcinoma of unknown primary. The registry records a start in 2009-02, primary completion in 2012-12, and enrollment of 89.
Progression-free survival was the primary endpoint. The registry posts median estimates of 5.4 months for Arm A and 5.3 months for Arm B, with 95% confidence intervals, but does not report a sponsor-reported primary comparison. Best overall response is the only named secondary outcome with results posted in this record; the comparison is unadjusted. Serious adverse event counts and selected terms are also recorded. The full analysis plan, detailed missing-data procedures, and results for the other named secondary outcomes are not reported in the registry record.