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 Study of Patients With Stage IV Malignant Melanoma Using PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma (NCT01462773), a na phase 1 study. The primary outcome is Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01462773 |
| Phase | Phase 1 |
| Condition | Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ohio State University Comprehensive Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with metastatic malignant melanoma; the title identifies stage IV disease. The registry record does not report further eligibility details such as age range, disease history, or prior treatment. It records enrollment of 16 participants.
Intervention
Participants received bortezomib, also called PS-341 or VELCADE, in combination with interferon-alpha-2b. The treatment description specifies intravenous bortezomib and subcutaneous interferon alfa-2b on a repeating schedule. Treatment could continue for 5 courses unless disease progression or unacceptable toxicity occurred.
Comparator
There was no separate comparator group. The record identifies a single-group study, with allocation listed as not applicable and masking listed as none. Thus, the study was designed to assess the combination regimen rather than to estimate a treatment contrast against a control.
Primary question
The primary question was whether and at what dose dose-limiting toxicities occurred when VELCADE was administered with interferon-alpha-2b to patients with metastatic malignant melanoma. The registry lists the primary outcome as the number of toxicities, assessed for up to 25 weeks or until disease progression. Numerical primary-outcome results are not reported in the registry record.
3. Trial Design
This was a phase I, completed, single-group study sponsored by Ohio State University Comprehensive Cancer Center. The registry lists enrollment of 16 and gives a start date of 2006-01 and primary completion date of 2010-10. Allocation was not applicable, and masking was none. Because there was no separate control group, the study does not provide a randomized or like-for-like comparison of the combination with another treatment.
The treatment description specifies bortezomib given intravenously over 3-5 seconds on days 1, 8, 15, and 22. Recombinant interferon alfa-2b was given subcutaneously on days 1, 3, and 5 during weeks 1-4, with days 1 and 3 only in week 4 of course 1. Treatment repeated every 5 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.
The registry describes a dose-escalation approach. Initially, three patients were to receive VELCADE at 1.0 mg/m2. If one of the three experienced a dose-limiting toxicity, an additional 3 patients were to be treated at that dose. If only one of the six experienced a dose-limiting toxicity, the next cohort of three was to receive 1.3 mg/m2. If two or more of the six experienced a dose-limiting toxicity, no further patients were to be treated at that dose level. The highest dose level at which fewer than 2 patients experienced dose-limiting toxicity was to be expanded to six patients.
The registry record does not report whether every planned step occurred, the dose level ultimately reached, or the number treated at each dose.
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 | Bortezomib & Interferon-a |
|---|---|
| STARTED | 16 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Treatment (Enzyme Inhibitor, Interferon Therapy) |
|---|---|---|
| Participants analysed | 16 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 12 |
| Age, Categorical: >=65 years | Participants | 4 |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 8 |
| Region of Enrollment: United States | patients | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma., measured over up to 25 weeks or until disease progression.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | toxicities |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of dose-limiting toxicities (DLTs) associated with bortezomib plus interferon-alpha-2b. The assessment period is listed as up to 25 weeks or until disease progression. A DLT is a treatment-related toxicity considered important to dose selection; in a phase I dose-escalation study, its frequency helps guide whether a dose level can be pursued or should not be escalated further. The record does not give the operational definition of a DLT, such as which events qualified or how severity and attribution were determined.
This endpoint serves the study’s stated purpose of assessing safety, tolerability, and DLTs for the combination. It differs from an endpoint designed to compare clinical benefit between treatment groups: this study has a single group and no separate comparator. The registry also lists objective antitumor responses and time to tumor progression as secondary outcomes, but numerical results for those outcomes are not reported in the registry record.
Although the dose-escalation rules are described, the registry record does not report the observed DLT count, the count at each dose level, or a final recommended dose. Consequently, the endpoint’s meaning can be explained from the protocol description, but its observed result cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s purpose and design, but it does not report numerical results for the primary DLT endpoint. It is therefore not possible to describe the observed DLT frequency, determine which dose levels met the stated escalation rules, or identify a dose selected by the study. The planned dose-escalation procedure is not itself an outcome: it describes how decisions were to be made in response to observed toxicities.
The study enrolled 16 participants in a single group receiving the combination. This enrollment figure does not supply the missing endpoint result. Nor does the adverse-event summary substitute for a DLT result. The record reports 0 serious adverse events among 16 at risk and 8 affected by other adverse events among 16 at risk. These are separate adverse-event summaries; the registry does not state that the other adverse events were DLTs, nor does it provide a mapping between the categories. The count of serious adverse events therefore should not be interpreted as the DLT count.
The lack of a comparator also limits the kinds of conclusions the design can support. The record can describe experience in the treated group, but it cannot isolate the effect of the combination relative to another regimen or no treatment. Likewise, the listed secondary aims—documenting objective antitumor responses and time to tumor progression—do not establish comparative efficacy, and their numerical results are not reported in the registry record.
Precision cannot be assessed for the primary endpoint because the record gives no DLT estimate or interval around an estimate. A confidence interval, in general, describes the uncertainty associated with an estimated quantity; without an endpoint estimate and its uncertainty, the precision of the DLT findings cannot be evaluated. The record also does not report analyses by dose level or a statistical analysis plan.
Accordingly, the defensible interpretation is limited: this was a completed phase I study with a described dose-escalation scheme and a listed enrollment of 16, but its registry record does not provide the principal toxicity result needed to assess what the study observed about dose-limiting toxicities.
9. Statistical Methods Explained
The statistical methods relevant to this study are primarily those used to organize dose escalation and summarize toxicity. The registry describes a rule-based design rather than a comparative treatment analysis. It does not report a statistical analysis plan, an inferential model, or numerical results for the primary endpoint.
How does the dose-escalation rule work?
The registry describes beginning with three patients at a VELCADE dose of 1.0 mg/m2. A DLT among that initial group triggers treatment of an additional 3 patients at the same dose. The record then describes how the observed count among six patients determines whether treatment can move to the next dose, stop at that dose, or expand the highest dose level with fewer than 2 DLTs. The next stated dose is 1.3 mg/m2.
In general, a rule-based escalation design uses observed toxicity counts in small groups to make successive dose decisions. It is not a randomized comparison of dose levels, and the group sizes and decision thresholds do not by themselves establish the underlying risk of toxicity with high precision. The registry calls the procedure a standard method, but does not provide details beyond the decision rules quoted in the record. It does not report whether the escalation proceeded exactly as planned or which dose level was ultimately selected.
What does a count endpoint tell the reader?
The primary outcome is expressed as a number of toxicities. A count records how many events meet the endpoint definition; interpreting it requires knowing the applicable assessment period, the population assessed, and what qualifies as a DLT. The registry gives the timeframe as up to 25 weeks or until disease progression, but does not report the DLT definition or the observed count. It also does not provide counts by dose level. These omissions prevent reconstruction of the dose-escalation decisions from the registry record.
In general, counts can be presented alongside the number of participants assessed to give context, but that context does not remove uncertainty. If event rates vary more than a simple statistical model expects, over-dispersion can make conventional uncertainty estimates too narrow. That is a general statistical consideration, not a finding reported for this study. No model for count variation or uncertainty interval is reported in the registry record.
Why is this not a treatment-effect comparison?
The record identifies a single group, allocation as not applicable, and no masking. There is no comparator arm for estimating a difference between assigned treatments. A single-group toxicity count can describe what was recorded among treated participants, but it cannot distinguish treatment effects from other influences on outcomes. General concepts such as a between-group effect estimate or a randomized contrast do not apply as observed comparisons in this design.
The registry also lists objective antitumor responses and time to tumor progression among the secondary outcomes. It does not report numerical results, the analysis methods for these outcomes, or any adjustment for multiple outcome testing. A time-to-event analysis can, in general, account for differing follow-up through methods that use event timing and censoring, but the registry record does not state which methods, if any, were used for time to tumor progression.
How should planning calculations be read?
A sample-size calculation is a planning illustration, not an observed result or a measure of the study’s achieved power. General power calculations depend on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not describe the actual single-group design and should not be read as its allocation or analysis plan. Any sample-size illustration based on an observed effect does not show that the study had that power, and it cannot replace the missing DLT estimate.
More broadly, statistical interpretation depends on transparent reporting of the endpoint definition, analysis population, missing observations, and uncertainty. The registry record does not report those details for the primary outcome. It also lists no analyses. Consequently, there is no reported estimate to recalculate or use for an independent check of the sponsor’s analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary toxicity endpoint and secondary outcomes concerning objective antitumor responses and time to tumor progression. It does not report how multiple outcomes were handled statistically, whether any outcome hierarchy was specified, or whether an adjustment for multiple testing was planned. Without that information, the record does not establish how to interpret a collection of outcome tests as a whole. This is particularly relevant when several outcomes are examined, because repeated testing can increase the chance of a result appearing notable by chance. That is a general statistical concern, not a reported analysis of this study.
The registry record does not report a statistical analysis plan or an analysis population for the primary endpoint. It does not specify how missing observations, early discontinuation, or incomplete toxicity assessments were handled. The treatment description allows treatment to stop in the event of progression or unacceptable toxicity, but the record does not explain how such circumstances entered the endpoint analysis.
The record lists enrollment of 16, while the adverse-event summary separately lists 16 at risk for serious events and 16 at risk for other adverse events. It does not provide an endpoint-specific denominator for DLT assessment. These figures should not be assumed to define the population included in every analysis.
No analyses are listed in the registry record. Numerical results for the primary and secondary outcomes, uncertainty estimates, and explanations of missing data are not reported in the registry record. As a result, readers cannot determine whether the reported enrollment corresponds to the population analyzed for each outcome or assess possible effects of missing observations.
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 |
|---|---|---|---|
| Treatment (Enzyme Inhibitor, Interferon Therapy) | 0 | 16 | 0.0% |
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 |
|---|---|
| Treatment (Enzyme Inhibitor, Interferon Therapy) | 8 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor, Interferon Therapy) |
|---|---|---|
| Fatigue | General disorders | 8 of 16 |
| Diarrhea | Gastrointestinal disorders | 3 of 16 |
| Vomiting | Gastrointestinal disorders | 3 of 16 |
| Lymphopenia | Investigations | 1 of 16 |
The adverse-event summary reports 0 serious adverse events among 16 at risk. It separately reports 8 affected by other adverse events among 16 at risk. These are the counts as recorded in the registry; they should be read as distinct categories in the summary, not combined into a DLT result. The registry does not state that the other adverse events met the study’s DLT definition.
The serious-event count is not evidence that no toxicity occurred: the same summary records other adverse events, and the primary DLT result is not reported in the registry record. The summary also does not provide event-level details, severity grades, attribution to study treatment, timing, or outcomes for these events. No serious-event terms are listed in the registry’s serious-event summary.
The adverse-event at-risk counts describe the denominators attached to this summary, not necessarily the denominator used for every study outcome. These figures provide limited descriptive information about recorded adverse events, but they do not allow a complete assessment of the safety profile or the dose-escalation endpoint.
12. What the Result Does, and Does Not, Mean
The study record documents a phase I investigation of bortezomib with interferon-alpha-2b in metastatic malignant melanoma. It describes a dose-escalation scheme intended to evaluate dose-limiting toxicities and lists an enrollment of 16. It also records adverse-event counts for serious and other events. These are useful details about the design and the posted safety summary.
The central result needed to answer the stated primary question—the observed number of DLTs—is not reported in the registry record. The record also does not report the DLT definition, counts by dose level, or final dose-escalation outcome. Therefore, it does not support a conclusion about which dose was tolerated under the study’s rules. The adverse-event figures cannot fill this gap because the registry does not identify the other adverse events as DLTs.
The single-group design does not estimate how outcomes would differ under a comparator treatment. It also does not establish that the combination caused any observed response or toxicity. The listed secondary outcomes concern objective antitumor responses and time to tumor progression, but their numerical results are not reported in the registry record. No comparative efficacy conclusion can be drawn from the available record.
More generally, a study’s completion status and enrollment do not establish that its aims were met or that its results are precise. Interpretation of a toxicity endpoint requires its observed value, its definition, the population assessed, and information about uncertainty and missing data. Those details are not reported in the registry record. The appropriate reading is therefore descriptive and limited: the record gives the study framework and some adverse-event counts, while leaving the primary toxicity result and the secondary outcome results unavailable.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary objective is dose finding rather than a randomized comparison of clinical outcomes. The study uses toxicity counts to guide dose escalation, with explicit rules for treating additional patients at a dose or moving to a stated next dose. This illustrates how a phase I design can connect observed safety information to decisions about dose levels.
At the same time, a decision rule is not a substitute for reporting the data that drove the decision. To understand the study’s statistical evidence, readers need the DLT definition, the observed counts at each dose, the number assessed at each dose, and the final dose-escalation outcome. Those results are not reported in the registry record. Without them, the central statistical purpose of the design cannot be evaluated from the registry record.
The single-group structure also clarifies the scope of inference. The design is suited to describing experience with the combination under the study’s procedures, not to estimating a randomized treatment contrast. The record’s listed enrollment and adverse-event summaries do not establish comparative benefit or provide the missing dose-specific DLT findings.
Finally, the record demonstrates why reporting completeness matters. A completed status indicates the registry’s status for the study, but does not itself communicate the endpoint estimate, uncertainty, or analysis population. Those elements are needed to judge how much information the observations provide. The posted record gives readers the design framework and limited safety counts, while leaving the primary result unreported.
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 most important limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. The DLT definition is also not reported, and there are no dose-specific toxicity counts or final dose-escalation outcome in the record. The planned escalation rules therefore cannot be checked against observed results.
The study is single group, with no separate comparator and no masking. It cannot provide a randomized comparison between the combination and another treatment. The record does not report how patients were selected, detailed eligibility criteria, baseline characteristics, or prior treatment, so the population represented by the enrollment figure cannot be further characterized from this record.
The registry’s adverse-event summary is limited: it gives counts for serious and other adverse events but does not provide event-level descriptions, severity, attribution, or timing. It also does not establish how these categories relate to DLTs. Numerical results for objective antitumor responses and time to tumor progression are not reported in the registry record.
Further limitations arise from absent analysis details. The registry record does not report the analysis population, handling of missing observations, uncertainty estimates, or a statistical analysis plan. It does not state whether the planned escalation proceeded as described. These gaps prevent assessment of endpoint precision, completeness of follow-up, and the robustness of the reported safety summary.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Patients With Stage IV Malignant Melanoma Using PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma — NCT01462773.
- Registry record last updated 2015-01-13; status last verified 2014-12.
- Results first posted 2014-12-30.
- 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
NCT01462773 is a completed phase I, single-group study sponsored by Ohio State University Comprehensive Cancer Center. The record lists enrollment of 16 and describes bortezomib plus interferon-alpha-2b for patients with metastatic malignant melanoma. The primary objective was to determine dose-limiting toxicities, with assessment up to 25 weeks or until disease progression.
The registry describes dose-escalation rules beginning at 1.0 mg/m2 and identifies 1.3 mg/m2 as the next stated dose. It reports 0 serious adverse events among 16 at risk and 8 affected by other adverse events among 16 at risk. Numerical results for the primary DLT endpoint and the listed secondary outcomes are not reported in the registry record.