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 Trial of Vandetanib (AZD6474) and Selumetinib (AZD6244) for Solid Tumours Including Non Small Cell Lung Cancer (VanSel-1) (NCT01586624), a non-randomized phase 1 study. The primary outcome is Number of Serious Adverse Events, Non-serious Adverse Events and Treatment Emergent Adverse Events..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01586624 |
| Phase | Phase 1 |
| Condition | Cancer, Non Small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 61 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Cancer Research UK |
| Results posted | Yes |
2. Clinical Question
The study asked whether vandetanib and selumetinib could be administered together, what dose and schedule might be suitable for further evaluation, and what safety and pharmacokinetic observations arose during treatment. The registry describes a dose-escalation phase involving patients with solid tumours and an expansion cohort involving patients with non-small cell lung cancer (NSCLC). Its primary outcome concerns serious, non-serious and treatment-emergent adverse events. The listed secondary outcomes include pharmacokinetic measures in the escalation cohorts and progression-free survival, one-year survival and tumour metabolism in the expansion cohort.
Population
Eligible patients with solid tumours could enter dose escalation; the expansion cohort was for patients with NSCLC. Safety assessment included patients who met eligibility criteria and received at least one dose of the combination treatment (N=57).
Intervention
Oral vandetanib and selumetinib in combination, with dose and schedule varying across escalation cohorts. The expansion phase used the stated recommended phase 2 dose of 200 mg OD vandetanib and 50 mg BD selumetinib.
Comparator
There was no randomized control group. The registry identifies a non-randomized, single-group model, so differences between cohorts do not constitute a like-for-like randomized comparison.
Primary question
What numbers of serious, non-serious and treatment-emergent adverse events were observed during treatment and follow-up? The registry also describes the trial’s aims as assessing whether the combination could be given safely and identifying a dose and schedule for further evaluation.
3. Trial Design
This was a Phase I, non-randomized, open-label, single-group study sponsored by Cancer Research UK. The registry lists enrollment of 61 and status as completed. It describes two parts: dose escalation in patients with solid tumours, followed by an expansion cohort for NSCLC. The study began on 2012-01-10, and primary completion is listed as 2020-06-11.
The dose-escalation cohorts tested different combinations of vandetanib and selumetinib doses and schedules. They included 100 mg OD vandetanib with 25 mg BD, 50 mg BD, or 75 mg BD selumetinib; 100 mg OD vandetanib with 100 mg OD or 125 mg OD selumetinib; and 200 mg OD or 300 mg OD vandetanib with 50 mg BD selumetinib. The expansion phase used 200 mg OD vandetanib with 50 mg BD selumetinib and is described as using the recommended phase 2 dose defined during escalation.
Because allocation was non-randomized and there was no control arm, the dose cohorts should not be treated as randomized treatment groups. Cohort differences could reflect their different doses, schedules, or enrolled patients; the registry record does not report a design that isolates these influences. The study’s stated aims include safety, dose and schedule selection, side effects and their management, and what happens to both drugs inside the body.
The safety population is described as all eligible patients who received at least one dose of the combination (N=57). That population definition differs from the overall enrollment figure. The registry record does not report further details explaining the difference.
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.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) |
|---|---|---|---|---|---|---|
| STARTED | 6 | 6 | 6 | 7 | 9 | 8 |
| COMPLETED | 2 | 2 | 1 | 0 | 1 | 0 |
| NOT COMPLETED | 4 | 4 | 5 | 7 | 8 | 8 |
Reasons for not completing this period:
| Reason | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) |
|---|---|---|---|---|---|---|
| Adverse Event | 3 | 0 | 2 | 1 | 3 | 3 |
| Physician Decision | 0 | 1 | 1 | 0 | 2 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Evidence of disease progression | 1 | 3 | 2 | 5 | 3 | 5 |
| Screen failure (no treatment received) | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All patients who met the eligibility criteria and received at least one dose of the combination treatment (vandetanib and selumetinib) were evaluable for safety assessment (N=57).
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.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib ) | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib ) | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 6 | 7 | 9 | 8 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 5 | 3 | 5 | 3 | 3 |
| Age, Categorical: >=65 years | Participants | 6 | 1 | 3 | 2 | 6 | 5 |
| Sex: Female, Male: Female | Participants | 3 | 2 | 4 | 4 | 2 | 6 |
| Sex: Female, Male: Male | Participants | 3 | 4 | 2 | 3 | 7 | 2 |
| Race and Ethnicity Not Collected | Participants | — | — | — | — | — | — |
| Region of Enrollment: United Kingdom | participants | 6 | 6 | 6 | 7 | 9 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Serious Adverse Events, Non-serious Adverse Events and Treatment Emergent Adverse Events., measured over Safety data was collected from the date of written informed consent and continued until 28 days after the final administration of vandetanib and selumetinib, an average (mean) of 164 days (approximately 5.4 months)..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the number of serious adverse events, non-serious adverse events and treatment-emergent adverse events. Safety data collection began at written informed consent and continued until 28 days after the final administration of vandetanib and selumetinib. The registry gives the average (mean) safety observation period as 164 days (approximately 5.4 months).
Counting adverse events is useful in an early-phase study because the stated aims include assessing whether the drug combination can be administered safely, identifying potential side effects, and informing dose and schedule selection. Event counts describe the observed safety experience in the people assessed; they do not by themselves establish that a drug caused an event. Nor do counts alone describe how long each person was observed, the severity or clinical course of every event, or the relative safety of the combination compared with another treatment.
The registry presents group-level numbers of patients at risk and affected for serious and other adverse events, along with deaths. These are safety summaries, not a randomized comparison. The registry record does not report an inferential analysis for the primary outcome, an event-rate model, or a prespecified method for handling repeated events in the same patient.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results show serious adverse events in every listed cohort. The cohort entries report affected and at-risk counts: 4 of 6 in Cohort 1, 4 of 6 in Cohort 2, 6 of 6 in Cohort 3, 2 of 7 in Cohort 4, 7 of 8 in Cohort 5a, 5 of 7 in Cohort 5b, 6 of 6 in Cohort 6, and 8 of 11 in the expansion phase. These are descriptive counts. They should not be read as estimates from a randomized comparison or as evidence that one dose is safer than another.
For non-serious adverse events, the registry reports all patients at risk as affected in each listed cohort: 6 of 6 in Cohorts 1, 2 and 3; 7 of 7 in Cohort 4; 8 of 8 in Cohort 5a; 7 of 7 in Cohort 5b; 6 of 6 in Cohort 6; and 11 of 11 in the expansion phase. The record also lists deaths by cohort: 0 in Cohort 1, 1 in Cohort 2, 2 in Cohort 3, 0 in Cohort 4, 1 in Cohort 5a, 0 in Cohort 5b, 1 in Cohort 6, and 7 in the expansion phase. The registry record does not state whether these deaths were considered related to treatment, so the counts should not be interpreted as treatment-caused deaths.
The registry lists serious-event terms including retinal detachment and rash acneiform, each at 50.0%; eye disorders - Other, specify, diarrhea, and presyncope, each at 33.3%; and rash maculo-papular at 27.3%. The record does not report the denominator or clarify how these term percentages relate to patients or events. They therefore need to be read as reported term summaries, not as directly comparable cohort-specific risks.
No efficacy result or treatment-effect analysis is reported in the posted results. Although progression-free survival, one-year survival and tumour metabolism appear among the expansion cohort’s secondary outcomes, the registry record does not report their results or analyses. The results support a description of the safety counts recorded for this study, but not a conclusion about comparative safety or efficacy.
9. Statistical Methods Explained
The registry describes a non-randomized, single-group Phase I study. Its results are principally counts rather than a single treatment-effect estimate. That distinction matters: an event count describes what was recorded among the assessed patients, while a comparative effect requires a defined contrast between groups and an analysis suited to that contrast. The record does not describe a randomized comparator, and its own note cautions that the arms are not a like-for-like control comparison.
What do the adverse-event counts represent?
For each cohort, the registry gives the number at risk and the number affected by serious adverse events, other adverse events, and deaths. A count is an absolute description of the posted safety experience. It is not automatically an event rate: rate calculations would require a defined time at risk and a specified event-counting approach. The registry gives a mean safety follow-up duration of 164 days (approximately 5.4 months), but does not report cohort-specific observation time or an analysis adjusting for differences in follow-up.
The event counts also do not necessarily equal the number of events. A patient may experience more than one event, but the registry record does not state how recurrent events are handled in the displayed count summaries. It does not report a model for event counts or a measure of uncertainty for the cohort counts. As a result, the counts can be read descriptively, but the record does not support claims about the precision of a modeled event rate.
Why is the study not a controlled comparison?
Random allocation can help make groups comparable on average, but this study is recorded as non-randomized and single-group. Its cohorts received different dose and schedule combinations, and the expansion cohort had a different stated purpose and population. Comparing their raw adverse-event counts would mix dose, schedule, cohort membership, and potentially patient characteristics. No causal contrast can be inferred from those counts alone. The record does not report an adjusted analysis intended to address such differences.
General statistical principle: when groups differ in their design or patient composition, a numerical contrast may reflect those differences as well as any treatment-related difference. A confidence interval, in general, expresses uncertainty around an estimate under the assumptions of the analysis used. The registry record does not report confidence intervals for the safety comparisons, and there is no reported comparative estimate to which one could attach a confidence interval.
What can be said about planning calculations?
The posted planning illustration is described as a calculation from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. For time-to-event outcomes, the illustration gives a total number of events; for other outcomes, it gives participants per arm. Such calculations are planning illustrations, not observed power and not evidence that the original trial was designed or sized according to those assumptions. The registry record does not report its own sample-size justification, and no trial-specific design rationale should be inferred from a planning calculation.
General statistical principle: a planning calculation depends on its assumptions, including the effect to detect, allocation, outcome type and chosen error rate. A change in those assumptions can change the planned sample size. These calculations do not remedy the lack of randomization or turn the cohorts into a controlled comparison.
What analyses are reported?
The registry lists 10 outcome measures and reports 0 analyses. The primary outcome is a count of adverse events, while the secondary outcomes include pharmacokinetic parameters for the escalation cohorts and progression-free survival, one-year survival, and tumour metabolism for the expansion cohort. The registry record does not report statistical models, hypothesis tests, confidence intervals, adjustment variables, or analysis results for these outcomes. Accordingly, the posted information supports descriptive interpretation of the adverse-event summaries, but not reconstruction of an inferential analysis.
General statistical principle: methods should match the type of outcome. Event counts, pharmacokinetic measurements, and time-to-event outcomes have different data structures and may call for different summaries and models. Without a reported analysis plan and outcome results, it is not appropriate to assume which methods were used or to substitute an unreported analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and multiple secondary outcomes. These cover pharmacokinetic measures in the dose-escalation cohorts and progression-free survival, one-year survival and tumour metabolism in the NSCLC expansion cohort. The record reports 0 analyses. It does not report whether hypotheses were tested, how many tests may have been performed, or whether any adjustment for multiple comparisons was planned or used. Therefore, the family of statistical tests and any multiplicity strategy are not reported in the registry record.
General statistical principle: when many outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. Prespecified priorities and multiplicity procedures can help readers interpret evidence across multiple tests. That general concern does not establish that a particular procedure was needed or used in this study; the registry record does not report one.
The safety population is defined as eligible patients who received at least one dose of the combination (N=57). The record does not report how missing safety observations were handled, whether any patients were excluded from particular outcome summaries, or how missing data were treated for the secondary outcomes. It also does not report an intention-to-treat analysis population or another analysis population for efficacy outcomes. The registry’s overall enrollment is 61, and the reason for the difference between enrollment and the stated safety population is not reported in the registry record.
Without those details, the posted counts should be interpreted for the population and outcome summaries explicitly described, rather than assumed to represent every enrolled patient or a broader target population. The record does not report sensitivity analyses assessing how missing or incomplete observations might affect results.
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 |
|---|---|---|---|
| Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | 4 | 6 | 66.7% |
| Dose Escalation Phase Cohort 2 ( Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | 4 | 6 | 66.7% |
| Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | 6 | 6 | 100.0% |
| Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | 2 | 7 | 28.6% |
| Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | 7 | 8 | 87.5% |
| Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | 5 | 7 | 71.4% |
| Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | 6 | 6 | 100.0% |
| Expansion Phase (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | 8 | 11 | 72.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | 0 of 6 |
| Dose Escalation Phase Cohort 2 ( Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | 1 of 6 |
| Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | 2 of 6 |
| Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | 0 of 7 |
| Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | 1 of 8 |
| Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | 0 of 7 |
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 |
|---|---|
| Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | 6 of 6 |
| Dose Escalation Phase Cohort 2 ( Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | 6 of 6 |
| Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | 6 of 6 |
| Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | 7 of 7 |
| Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | 8 of 8 |
| Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | 7 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose Escalation Phase Cohort 2 ( Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) |
|---|---|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 2 of 6 | 2 of 6 | 1 of 6 | 0 of 7 | 2 of 8 | 0 of 7 |
| Retinal detachment | Eye disorders | 0 of 6 | 0 of 6 | 2 of 6 | 0 of 7 | 3 of 8 | 1 of 7 |
| Retinopathy | Eye disorders | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 7 | 1 of 8 | 1 of 7 |
| Abdominal pain | Gastrointestinal disorders | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 7 | 1 of 8 | 0 of 7 |
| Lung infection | Infections and infestations | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 7 | 1 of 8 | 0 of 7 |
| Injury, poisoning and procedural complications - Other, specify | Injury, poisoning and procedural complications | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 7 | 0 of 8 | 1 of 7 |
| Vomiting | Gastrointestinal disorders | 1 of 6 | 0 of 6 | 0 of 6 | 0 of 7 | 1 of 8 | 0 of 7 |
| Disease Progression | General disorders | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 7 | 0 of 8 | 0 of 7 |
| Biliary tract infection | Infections and infestations | 0 of 6 | 0 of 6 | 0 of 6 | 1 of 7 | 1 of 8 | 0 of 7 |
| Infections and infestations - Other, specify | Infections and infestations | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 7 | 0 of 8 | 1 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose Escalation Phase Cohort 2 ( Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) |
|---|---|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 5 of 6 | 5 of 6 | 5 of 6 | 4 of 7 | 5 of 8 | 7 of 7 |
| Nausea | Gastrointestinal disorders | 4 of 6 | 3 of 6 | 3 of 6 | 5 of 7 | 4 of 8 | 4 of 7 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 5 of 6 | 3 of 6 | 2 of 6 | 4 of 7 | 5 of 8 | 3 of 7 |
| Fatigue | General disorders | 3 of 6 | 5 of 6 | 5 of 6 | 3 of 7 | 3 of 8 | 2 of 7 |
| Vomiting | Gastrointestinal disorders | 4 of 6 | 2 of 6 | 3 of 6 | 5 of 7 | 1 of 8 | 4 of 7 |
| Anorexia | Metabolism and nutrition disorders | 4 of 6 | 1 of 6 | 1 of 6 | 1 of 7 | 3 of 8 | 3 of 7 |
| Constipation | Gastrointestinal disorders | 2 of 6 | 3 of 6 | 1 of 6 | 2 of 7 | 2 of 8 | 2 of 7 |
| Abdominal pain | Gastrointestinal disorders | 3 of 6 | 0 of 6 | 0 of 6 | 1 of 7 | 3 of 8 | 3 of 7 |
| Infections and infestations - Other, specify | Infections and infestations | 3 of 6 | 0 of 6 | 2 of 6 | 1 of 7 | 3 of 8 | 1 of 7 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 6 | 2 of 6 | 1 of 6 | 1 of 7 | 3 of 8 | 1 of 7 |
Serious events with the highest arm-level rate: retinal detachment (50.0%), rash acneiform (50.0%), eye disorders - other, specify (33.3%), diarrhea (33.3%), presyncope (33.3%).
The serious adverse-event entries give both the number of patients at risk and the number affected within each cohort. The posted counts are 4 of 6 in Cohort 1, 4 of 6 in Cohort 2, 6 of 6 in Cohort 3, 2 of 7 in Cohort 4, 7 of 8 in Cohort 5a, 5 of 7 in Cohort 5b, 6 of 6 in Cohort 6, and 8 of 11 in the expansion phase. These are cohort-specific descriptive figures; they are not a randomized comparison.
The registry also lists deaths by cohort, but does not report whether they were attributed to treatment. A death count should not be treated as a count of treatment-related deaths unless the record explicitly identifies that relationship. The record does not report the causes or timing of the listed deaths.
The serious-event term list includes percentages, but the registry record does not report the denominator or the precise basis for those percentages. They should not be assumed to be incidence estimates for the whole safety population or to be comparable across cohorts. More generally, counts are affected by cohort size and observation time; the registry reports a mean safety follow-up duration of 164 days (approximately 5.4 months), but not cohort-specific follow-up. These limitations make descriptive reading more appropriate than ranking cohorts by apparent safety.
12. What the Result Does, and Does Not, Mean
The registry results describe safety observations from a Phase I combination study with dose escalation in solid tumours and an NSCLC expansion cohort. The posted adverse-event figures show that serious and other adverse events were recorded in the cohorts, alongside the reported death counts. Those observations are relevant to the study’s stated safety aims and provide descriptive information about the treated patients included in the safety assessment.
They do not establish whether vandetanib and selumetinib are more or less safe than another treatment, because the study has no randomized control group. Nor do cohort differences establish a dose-response relationship: the cohorts were non-randomized, tested different dose and schedule combinations, and were not described as a like-for-like comparison. The registry record does not report an adjusted comparative analysis.
The results also do not establish efficacy. The record names progression-free survival, one-year survival and tumour metabolism as secondary outcomes for the expansion cohort, but does not report their results or analyses. Listing an outcome is not the same as demonstrating an observed treatment effect. No conclusion about benefit or lack of benefit follows from the safety counts alone.
In general, a small early-phase study can provide descriptive observations that inform later investigation, while leaving substantial uncertainty about comparative effects. That is a general interpretation of study design, not a claim about an unreported protocol decision. The registry record does not report a sample-size justification, statistical analysis plan, inferential results, or missing-data methods. The posted information is therefore best read as a record of the study design and reported safety counts, with the limits of non-randomized, single-group evidence kept in view.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way it combines dose escalation with an expansion cohort while using a non-randomized, single-group design. The escalation phase records safety experience across several dose and schedule combinations, while the expansion phase applies the stated recommended phase 2 dose in an NSCLC cohort. Those purposes make descriptive safety and pharmacokinetic information central to the record.
The design also illustrates why numerical differences between cohorts need careful interpretation. The cohorts are not randomized controls, and the expansion cohort has a distinct disease population and role in the study. A difference in observed adverse-event counts cannot be separated from differences in dose, schedule, patient characteristics, and observation without an appropriate design and analysis. The registry itself cautions that the arms are not a like-for-like control comparison.
For biostatisticians and clinical researchers, the record highlights the need to distinguish counts from rates, event summaries from comparative effects, and planning calculations from observed evidence. It also shows why analysis populations, handling of missing data, and definitions for event-term percentages matter for reproducibility and interpretation. The registry does not report those methodological details or statistical analyses, so they cannot be presumed.
The trial’s listed secondary outcomes span pharmacokinetic and clinical measures, but outcome listing alone does not provide results. Keeping the design and reporting boundaries explicit helps readers avoid interpreting safety summaries as efficacy evidence or as proof of differences between dose cohorts.
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 central limitation is the absence of randomization and a control group. The registry identifies the study as non-randomized and single-group, and explicitly notes that the arms are not a like-for-like control comparison. Cohort counts therefore cannot establish comparative treatment effects.
The study includes different doses and schedules in dose escalation, followed by a distinct NSCLC expansion cohort. These cohorts may differ in more than dose, and the record does not report adjustment for cohort or patient characteristics. The posted summaries are counts; the registry does not report uncertainty intervals, comparative models, or an approach to repeated events.
Safety follow-up is described by a mean of 164 days (approximately 5.4 months), but cohort-specific follow-up is not reported. The registry lists deaths but does not report their causes or relationship to treatment. It also lists percentages for serious-event terms without reporting the denominator or exact calculation basis.
The record states that the safety population included eligible patients who received at least one dose (N=57), while overall enrollment is 61; reasons for the difference are not reported in the registry record. Missing-data methods and analysis populations for secondary outcomes are also not reported. Although secondary clinical outcomes are listed, their results are not reported, and the registry lists 0 analyses. A sample-size justification, statistical analysis plan, and multiplicity approach are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase I Trial of Vandetanib (AZD6474) and Selumetinib (AZD6244) for Solid Tumours Including Non Small Cell Lung Cancer (VanSel-1) — NCT01586624.
- Registry record last updated 2021-10-07; status last verified 2021-09.
- Results first posted 2021-10-07.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This completed Phase I study evaluated vandetanib with selumetinib in a non-randomized, single-group design. Its dose-escalation phase involved patients with solid tumours and its expansion phase involved patients with NSCLC. The registry lists enrollment of 61 and a safety population of eligible patients receiving at least one dose (N=57).
The primary outcome concerns serious, non-serious and treatment-emergent adverse events. The posted cohort summaries report patients at risk and affected, as well as deaths. Secondary outcomes include pharmacokinetic measures and NSCLC expansion outcomes, but their results are not reported. The registry lists 0 analyses.
Because there is no randomized comparator, cohort safety counts are descriptive rather than like-for-like treatment comparisons. The registry record does not report a sample-size justification, analysis plan, multiplicity method, or missing-data approach.