Biochemotherapy With Temozolomide for Metastatic Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Biochemotherapy With Temozolomide for Metastatic Melanoma (NCT00505635), a na phase 2 study. The primary outcome is Time to Progression (TTP).

2. Clinical Question

The registry also lists the number of participants with response as a secondary outcome. That outcome could describe tumor response, but its result and definition are not reported in the registry record. Safety was another stated objective. The record identifies serious adverse-event categories and term-specific percentages, but it does not provide enough detail to reconstruct a complete safety profile or determine how events were assessed over time.

Because the trial enrolled a small group and had no comparator, its clinical question is descriptive: what outcomes and safety events were recorded among participants receiving this regimen? It cannot directly establish whether outcomes differed from those under another treatment. The registry status is terminated, and the reason for termination is not reported in the registry record.

3. Trial Design

This was a phase 2, single-group study of biochemotherapy with temozolomide for metastatic melanoma. The registry lists enrollment as 5 and identifies M.D. Anderson Cancer Center as the sponsor. The study began in 2007-03, had a primary completion date of 2010-04, and is now listed as terminated. The reason for termination is not reported in the registry record.

Allocation is recorded as not applicable, consistent with the single-group design, and masking is listed as none. There was no separate control arm and no randomized contrast. Participants in the named treatment group received a multi-agent regimen including temozolomide, vinblastine, cisplatin, interleukin-2, interferon-alpha, and thalidomide. The arm description specifies temozolomide 250 mg/m^2 every 4 hours on Day 1; vinblastine 1.5 mg/m^2 intravenously on Days 1-4; cisplatin 20 mg/m^2 intravenously on Days 1-4; interleukin-2 9 MIU/m^2 intravenously over 24 Hours for 4 Doses on Days 1-4; interferon-alpha 5 mu/m^2 subcutaneously daily on Days 1-5; and oral thalidomide 400 mg daily. The official title mentions optional intrathecal interleukin-2, but the registry record does not describe how that option was applied.

The primary outcome was time to progression, measured from first dose to the first documented objective tumor progression. The specified timeframe refers to following two 21 day cycles until disease progression; the outcome description also says response evaluation by RECIST was done following 2 cycles and 3 cycles. The registry record does not report a numerical primary outcome result, participant-level data, or an analysis population. It lists response as a secondary outcome but does not report the result. Further details about eligibility, treatment discontinuation, follow-up completeness, and the reason the trial ended are not reported in the registry record.

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

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 Time to Progression (TTP), measured over Following two 21 day cycles until disease progression.

Time to progression (TTP) is the primary outcome. The registry defines it as the time, in days, from the first dose of study medication to the first documentation of objective tumor progression. Progression is defined using RECIST as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. Response evaluation is described as occurring following 2 cycles and 3 cycles.

Time-to-progression outcomes are used to describe how long participants remain without documented progression under the study’s assessment process. They incorporate both the timing of progression and the rules used to identify it. This is a general statistical explanation; the registry record does not report the actual assessment schedule beyond its description of evaluations after treatment cycles, nor does it give participant-level progression times.

The planned summary is a geometric mean with a full range. In general, a geometric mean summarizes positive measurements on a multiplicative scale, while a full range gives the smallest and largest observed values. This differs from reporting an arithmetic mean and standard deviation. The numerical geometric mean and range for this trial are not reported in the registry record. The record also does not explain whether participants without documented progression were censored, how censoring was handled, or whether the stated summary was calculated for every enrolled participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information recorded for this trial is limited. The registry identifies the primary endpoint and the form of its summary, but does not report a numerical endpoint result, a confidence interval, or an inferential test. It lists no analyses. Accordingly, there is no reported statistical estimate to interpret as a treatment effect, and there is no reported analysis that can be independently compared with the sponsor’s analysis.

What does a geometric mean describe?

In general, the geometric mean summarizes positive measurements using their multiplicative scale rather than their additive scale. It can be useful when times or other positive outcomes have a distribution for which multiplicative differences are meaningful. It should not be read as an arithmetic average. Here the registry specifies a geometric mean and full range for time to progression, but the values themselves are not reported in the registry record. Without those values, the endpoint’s location and spread cannot be described quantitatively.

A full range refers generally to the lowest and highest observed measurements. It does not by itself show the distribution between those endpoints, how many observations are near either extreme, or the precision of the estimate. A range can be especially sensitive to individual observations. The registry does not report the component progression times or additional summaries that would describe their distribution.

How should a time-to-progression endpoint be understood?

As a general concept, a time-to-event endpoint measures the time from a defined starting point until an event occurs. In this study, the starting point is the date of the first dose and the event is the first documentation of objective tumor progression under the stated RECIST definition. A time-to-event analysis often needs rules for participants whose event is not observed during follow-up, because their eventual event time is unknown. Such observations may be censored under a prespecified method. The registry record does not report whether any participants were censored or how censoring was handled.

The registry describes evaluations following 2 cycles and 3 cycles and gives the timeframe as following two 21 day cycles until progression. In general, when disease status is assessed at scheduled visits rather than continuously, the recorded progression date can depend on the timing of those assessments. The registry does not give further assessment-schedule details, so the exact timing conventions cannot be evaluated. The outcome description defines the event but does not specify a statistical model or method for summarizing censored observations.

What does the single-group design allow?

A single-group design can describe outcomes among participants who received a regimen. It does not directly estimate a contrast with a separate treatment group. A comparative treatment effect requires a comparator and an analysis that accounts for the design. Since this study has no separate comparator, its outcome data cannot yield a randomized between-group estimate. This is a general design principle, not a judgment about the clinical value of the study question.

Allocation is listed as not applicable, and masking as none. The record does not describe an allocation procedure because no allocation between groups is listed. It also does not report additional measures to reduce bias in outcome assessment. No assumptions about such procedures can be made from the registry information.

What do the planning assumptions mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s own design rationale. The sample-size values for the illustrations are not reported in the registry record, and the record does not give the outcome estimate needed to evaluate the illustrations in this account.

In general, sample-size planning asks how much information a future study would need to detect a chosen effect under specified assumptions. Such an illustration is not an estimate of what the current study found. It is also not observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty. The record does not report a sample-size justification for this trial, and no protocol or analysis plan details are available to explain whether the planning assumptions match the original study design.

The stated planning framework refers to two arms despite this trial being single-group. That distinction matters: a hypothetical future two-arm planning exercise does not create a control group in the completed trial and does not support a comparative conclusion from this record. No sample-size illustration should be interpreted as evidence that the single-group study had a specified ability to detect an effect.

What uncertainty can be assessed?

A confidence interval is, in general, a range of values generated by a statistical procedure intended to reflect uncertainty in an estimate under that procedure’s assumptions. It is not reported for the primary outcome in the registry record. Without an estimate and uncertainty interval, readers cannot assess the precision of the primary endpoint from the record. The small enrollment listed also means that any estimate based on this group would be grounded in limited observed information, although the exact analysis denominator and outcome completeness are not reported.

Over-dispersion is a general issue in count-data analysis: observed variability can exceed what a simple probability model assumes. Accounting for it can prevent overly narrow uncertainty estimates when counts are more variable than the model allows. The registry does not report a count-data model or inferential analysis for the response outcome, so over-dispersion is not a stated feature of the trial’s reported analysis. It should not be assumed that such a model was used.

Multiplicity arises when many outcomes, comparisons, or analyses are examined, increasing the chance of at least one apparently notable result under repeated testing. General approaches include prespecifying a primary endpoint or adjusting interpretation for multiple tests. This record names a primary outcome and a secondary response outcome but does not report a multiplicity strategy. The analysis count is listed as zero, and no numerical outcome analyses are reported. It is therefore not possible to determine whether additional analyses were planned or how they would have been handled.

In summary, the registry’s endpoint definition allows readers to understand what was intended to be measured, but the absence of numerical results and analysis details prevents assessment of the estimate, its precision, and the statistical procedures applied. Censoring, missing data, analysis populations, and the handling of repeated or multiple outcomes are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies time to progression as the primary outcome and number of participants with response as a secondary outcome. It does not report numerical results for either outcome, and it does not describe a multiplicity strategy. In general, multiplicity matters when several outcomes or analyses are tested, because repeated testing can increase the chance of a statistically notable result. No correction, hierarchical testing plan, or other approach is reported in the registry record. Since no analyses are listed, the record does not show how any multiplicity issue was handled.

The analysis populations are not described. The record does not say whether the primary outcome was analyzed among all enrolled participants, among participants who received treatment, or in another defined group. It does not report an outcome denominator or identify participants excluded from any analysis. The planned regimen includes multiple drugs, but the registry does not describe adherence, treatment discontinuation, or how those matters would affect analysis populations.

Missing-data procedures are also not reported in the registry record. For time to progression, the record does not explain how follow-up ending before documented progression was treated, whether any observations were censored, or how incomplete assessments were addressed. For the response outcome, it does not state how missing response evaluations were handled. These omissions matter because the interpretation of both outcomes can depend on whether all participants are assessed and how incomplete observations are classified.

The registry status is terminated, but the reason is not reported. The record does not state whether the termination affected the planned analyses or follow-up. No protocol-based statistical plan, interim-analysis procedure, or sample-size justification is reported. As a result, the registry record does not permit readers to verify whether the posted outcome reporting follows a prespecified analysis plan.

11. 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: neutropenia (100.0%), fatigue (80.0%), thrombocytopenia (60.0%), fever/rigor (20.0%), hemoglobin level (20.0%).

The registry lists one treatment group, with 5 participants at risk for serious adverse events and 5 recorded as affected. It also lists 5 at risk and 5 affected for other adverse events. The record does not explain the event definitions, collection window, severity grading, or whether participants could contribute more than one event. These entries therefore should not be interpreted as a complete description of event counts or clinical severity.

The serious adverse-event terms listed are neutropenia at 100.0%, fatigue at 80.0%, thrombocytopenia at 60.0%, fever/rigor at 20.0%, and hemoglobin level at 20.0%. The registry record does not provide further definitions for these terms or explain the denominator used for each percentage. The entries describe the registry’s reported safety categories; they do not indicate timing, duration, seriousness criteria for each term, or attribution to a particular drug.

Deaths are not reported in the registry record. The listed percentages should not be extended beyond the group and reporting context described by the registry, and they do not establish comparative safety because no control group is present. Missing event details and the absence of a complete safety analysis limit interpretation.

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

The record establishes that a phase 2, single-group study of a multi-drug regimen for metastatic melanoma was registered and that enrollment was 5. It identifies time to progression as the primary outcome and provides a definition based on first dose and documented objective progression under RECIST. It also lists a response outcome and selected serious adverse-event entries. Those details describe the study’s question and selected reported information; they are not a numerical account of the primary outcome.

The primary time-to-progression result is not reported in the registry record. The response outcome result is also not reported. Without those results, readers cannot determine the observed time to progression or the reported number of participants with response. There is no reported confidence interval or statistical test for the primary endpoint from which to assess precision or uncertainty.

The single-group design does not provide a randomized comparison with another treatment or with no treatment. Therefore, the record cannot support a causal comparison of outcomes between treatment options. This does not mean the regimen did or did not have an effect; it means the design and reported results do not provide the evidence needed to estimate a comparative effect.

The registry’s safety entries are also limited. They name several serious adverse-event terms and percentages, but do not explain their assessment period, grading, attribution, or detailed event counts. The record does not provide a complete accounting of possible harms or a comparison against another group. The reason for termination is not reported, so the status alone does not establish why the study ended.

In general, a result is more informative when its estimate, uncertainty, population, and analysis methods are all reported. Those elements are incomplete. The record supports a description of the registered design, endpoint definition, treatment regimen, and selected safety reporting, but not a conclusion about treatment effectiveness, comparative benefit, or the balance of benefits and harms.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly named time-to-progression endpoint and the absence of a numerical endpoint result in the registry record. An endpoint definition tells readers what event was intended to be measured, but without the observed summary and its uncertainty it cannot show the magnitude or precision of the outcome. The record specifies a geometric mean and full range, yet reports neither numerical value.

The single-group design is another important feature. Such a design can describe what was recorded among participants receiving a regimen, but it cannot provide a randomized estimate of how outcomes compare with a different treatment. This distinction is fundamental when interpreting clinical research: an outcome observed in a treatment group is not itself a comparative treatment effect.

The enrollment listed as 5 also makes transparent reporting especially important. In general, small studies can yield imprecise estimates, and individual observations can have substantial influence on summaries such as a range. The registry record does not provide estimates or uncertainty intervals that would allow readers to evaluate precision in this case. No additional numerical inference should be substituted for those missing results.

Finally, the record makes clear that planning illustrations based on an observed effect are separate from observed trial outcomes. Planning assumptions involving a hypothetical two-arm design do not turn this study into a controlled comparison or establish observed power. The statistical lesson is to keep design, planning calculations, outcome estimates, and safety descriptions distinct. In this record, the design and endpoint are described, but the key outcome results and several analysis details are not reported.

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 limitations are specific to the information recorded for this trial. The primary outcome result is not reported, despite the registry specifying time to progression as the primary endpoint and defining its measurement. The secondary outcome, number of participants with response, is also listed without a numerical result. The record therefore does not permit a quantitative assessment of either outcome.

The trial has one treatment group and no comparator. It cannot provide a direct randomized comparison, and the registry does not identify another concurrent group for contextual comparison. The enrollment is listed as 5, but the analysis population and endpoint denominators are not reported. The record does not indicate whether all enrolled participants were included in each outcome assessment.

Further endpoint details are missing. The registry does not describe censoring rules, handling of incomplete follow-up, missing response assessments, or a statistical model. It mentions RECIST evaluations following 2 cycles and 3 cycles and gives a timeframe following two 21 day cycles until progression, but does not provide additional assessment logistics. This limits assessment of how progression times were recorded and summarized.

Safety reporting is incomplete for interpretation. The registry lists serious-event categories and percentages, but does not provide their definitions, timing, duration, severity grades, attribution, or the denominator for each term-specific percentage. Deaths are not reported in the registry record. The reason for termination is also not reported, so no explanation for the trial status can be inferred.

Finally, the record does not report the protocol, sample-size justification, interim analyses, or a full statistical analysis plan. It lists no analyses and does not state how multiplicity or analysis populations were addressed. These omissions prevent readers from assessing whether the reported record matches a prespecified plan or how uncertainty and incomplete observations were handled.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Biochemotherapy With Temozolomide for Metastatic Melanoma — NCT00505635.
• Registry record last updated 2020-09-24; status last verified 2020-09.
• Results first posted 2012-04-18.
• 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.

18. Record Summary

NCT00505635 is a phase 2, single-group study sponsored by M.D. Anderson Cancer Center. It examined a regimen of temozolomide, vinblastine, cisplatin, interleukin-2, interferon-alpha, and thalidomide for metastatic melanoma. The registry lists enrollment as 5, a start date of 2007-03, a primary completion date of 2010-04, and current status as terminated. The reason for termination is not reported in the registry record.

The primary endpoint is time to progression, defined from first dose to first documented objective tumor progression using RECIST. The registry specifies a geometric mean and full range but does not report the numerical result. Number of participants with response is listed as a secondary outcome, with no result reported. Selected serious adverse-event terms and percentages are recorded, but detailed safety definitions and analysis information are not reported.

There is no separate comparator group. The registry record does not report an analysis population, missing-data procedures, censoring methods, or a statistical analysis plan. It therefore provides design and endpoint information but not enough outcome data for a quantitative efficacy interpretation or a comparative treatment conclusion.