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 Lower Dose Chemotherapy Given More Frequent With Avastin to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer (NCT00655850), a na phase 2 study. The primary outcome is Progression-Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00655850 |
| Phase | Phase 2 |
| Condition | Non-Small Cell Lung Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 39 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Alabama at Birmingham |
| Results posted | Yes |
2. Clinical Question
The trial asked whether progression-free survival could be characterized among participants with advanced non-squamous non-small cell lung cancer treated with metronomic chemotherapy and Avastin. The registry describes the intended population as chemotherapy-naïve and includes advanced or metastatic disease; its summary names Stage IIIB with pleural effusion or Stage IV disease. The primary endpoint was progression-free survival from treatment start to disease progression under the stated RECIST v1.0 definition.
Population
Participants with advanced, chemotherapy-naïve, non-squamous non-small cell lung cancer. The registry summary describes advanced or metastatic disease, including Stage IIIB with pleural effusion or Stage IV.
Intervention
Metronomic paclitaxel and gemcitabine, combined with Avastin. The regimen description specifies weekly chemotherapy for 3 out of 4 weeks and Avastin every 2 weeks.
Comparator
There was no separate comparator group. The trial is listed as a single-group study with allocation recorded as NA.
Primary question
What was the progression-free survival experience, measured from treatment start to progression under RECIST v1.0? The registry record does not report the median estimate or its 95% confidence interval.
This is a descriptive treatment-group question, not a randomized comparison of treatment strategies. Without a control group, the study cannot directly estimate how the observed outcome differs from an alternative treatment or from the course of disease without this regimen. The registry also notes an interest in assessing markers, but the marker results are not reported in the registry record. The record lists overall survival, objective response rate, and adverse events as secondary outcomes; their numerical results are not reported in the registry record.
3. Trial Design
The registry identifies NCT00655850 as a Phase II study sponsored by the University of Alabama at Birmingham. It is recorded as completed, with a start date of 2008-03 and primary completion recorded as 2015-09. Enrollment is listed as 39. The design is single group, allocation is NA, and masking is none. These features mean that the record describes one treatment group without a randomized or masked comparison.
The treatment group is named Paclitaxel and Gemcitabine + Avastin. The regimen description says paclitaxel and gemcitabine were given weekly for 3 out of 4 weeks, with each 4-week period constituting a cycle, while Avastin was administered every 2 weeks. It describes continuing treatment for a total of 6 cycles, but the regimen text is cut off after the word “unless”; the condition that follows is not reported in the registry record. The record does not give further details about dose levels, dose modifications, or treatment discontinuation rules.
The primary endpoint is progression-free survival, with a timeframe listed as baseline to 24 months. The endpoint description defines the measure as time from treatment start to disease progression in accordance with RECIST v1.0. The registry record does not report the primary endpoint estimate, its 95% confidence interval, or sponsor-reported hazard ratios. It also does not report how many participants contributed data to the primary endpoint analysis or how the follow-up period was handled in analysis.
Enrollment of 39 and the adverse-event risk group of 36 refer to different record entries; the registry does not explain their relationship. The record lists adverse events, overall survival, and objective response rate as secondary outcomes. Numerical results for these outcomes are not reported in the registry record. No sample-size justification, interim analysis plan, or fuller statistical analysis plan is 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.
Before assignment: This study is being done to determine the overall progression-free survival (PFS) in patients with advanced or metastatic (Stage IIIB - pleural effusion/IV), non-squamous histology Non-Small Cell Lung Cancer (NSCLC) treated with metronomic chemotherapy plus Avastin.
Overall Study
| Stage | Paclitaxel and Gemcitabine + Avastin |
|---|---|
| STARTED | 39 |
| COMPLETED | 36 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Paclitaxel and Gemcitabine + Avastin |
|---|---|
| Death | 2 |
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants with advanced chemotherapy naïve with non-squamous non-small cell lung cancer.
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.
Population: Patients were required to be over 18 years of age, have stage IV, histologically proven non-squamous NSCLC, have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, have received no prior systemic therapy for cancer, and have adequate organ function.
| Characteristic | Unit | Paclitaxel and Gemcitabine + Avastin |
|---|---|---|
| Participants analysed | 39 | |
| Age, Continuous | years | 59.5 (37 to 76) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 16 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 |
| Race (NIH/OMB): White | Participants | 31 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 39 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-Free Survival (PFS), measured over Baseline to 24 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) is the primary endpoint. The registry defines it as the number of days from the day a participant started treatment to the day disease progression occurred according to RECIST v1.0. Under that description, progression is indicated by a 20% increase in total tumor measurement over the nadir value or the appearance of new lesions. The timeframe is listed as baseline to 24 months, and the intended summary measure is the median with a 95% confidence interval.
General: A time-to-event endpoint records how long it takes for a specified event to occur. It can retain information about event timing, rather than reducing each participant's experience to a simple event/no-event result. The median is the time by which half of the relevant event-time distribution has occurred, when it can be estimated. A confidence interval expresses uncertainty around an estimate; it indicates a range of values compatible with the data under the analysis method and its assumptions. It does not guarantee that the true value lies in that range.
In this record, the median PFS and its 95% confidence interval are not reported in the registry record. The description specifies progression as the event, but does not state whether or how deaths without recorded progression were incorporated. That detail, along with censoring rules and the analysis population, is not reported in the registry record. Consequently, the endpoint definition can be described, but the numerical PFS experience cannot be interpreted from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The design and endpoint are identifiable: this was a single-group Phase II study of metronomic paclitaxel and gemcitabine with Avastin, with progression-free survival designated as the primary outcome. However, the registry record does not report a median PFS estimate or its 95% confidence interval. It therefore does not permit a numerical description of the primary outcome's magnitude or precision. No sponsor-reported hazard ratio or analysis estimate is reported in the registry record.
That absence matters for interpretation. A study can specify an outcome and a summary method without posting the resulting estimate. In this record, the endpoint definition and timeframe do not substitute for the observed event-time results. The completed status and enrollment of 39 do not reveal how many participants experienced progression, how long follow-up lasted for each participant, or what the estimated PFS distribution was. Those details are not reported in the registry record.
The single-group structure also limits what the design can establish. It can describe outcomes among participants treated with the regimen, if those results are reported, but it has no separate control arm for a direct treatment comparison. Allocation is listed as NA and masking as none. The registry’s own note warns that this is not a randomized comparison and that arms are not a like-for-like control comparison. Here there is only one listed treatment group, so claims about comparative benefit cannot be drawn from a between-arm estimate.
The safety entries report 25 participants with serious adverse events among 36 at risk, 36 with other adverse events among 36 at risk, and 2 deaths. The registry also lists selected serious-event terms with percentages. These are safety descriptions, not estimates of treatment effect. The record does not establish whether the reported deaths were caused by treatment, and it does not provide comparative safety data. The relationship between enrollment of 39 and the 36 participants listed at risk is not explained.
General: Statistical precision depends on both the estimate and the information contributing to it. A confidence interval would help readers judge how much uncertainty surrounds the estimated median, while event counts and follow-up information would help explain the data supporting that estimate. Since these results are absent, the magnitude and precision of PFS remain unknown from the registry record. The posted record supports a description of the trial's question, design, regimen, and some safety counts, but not a conclusion about the size of the PFS result or a causal comparison with another approach.
9. Statistical Methods Explained
Progression-free survival is a time-to-event outcome. The registry identifies the event as disease progression under RECIST v1.0 and defines the clock as beginning at treatment start. Its stated progression criteria are a 20% increase in total tumor measurement over nadir or the appearance of new lesions. The registry lists baseline to 24 months as the timeframe and the median with a 95% confidence interval as the intended summary. It does not report an estimated median or interval.
What does a median time-to-event estimate convey?
General: A median time-to-event estimate describes the point at which half of the event-time distribution has been reached, if the data and follow-up allow that point to be estimated. It is a summary of the distribution, not a statement that every participant experienced the event at that time. Participants may have different event times, and some may not have a recorded event during their observed follow-up.
General: Time-to-event methods can account for participants whose event time is not observed before their follow-up ends. Such observations are commonly described as censored. The method used to account for censoring, the censoring rules, and the amount of follow-up are not reported in the registry record. The record also does not specify whether death without documented progression counted as an event for this PFS endpoint. Without these details and the estimate itself, the endpoint cannot be independently interpreted beyond its posted definition.
How should a 95% confidence interval be read?
General: A confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval generally indicates greater precision than a wider interval, but the interval does not describe all possible sources of uncertainty, such as bias from study design or incomplete reporting. Nor does it mean that there is a 95% probability that the particular interval contains the true value. The registry names a 95% confidence interval for PFS but does not report its limits.
What can the study design say about comparison?
The registry lists a single-group model, allocation NA, and no masking. No separate control group is listed. General: A treatment-group outcome is descriptive; a comparative effect requires a suitable contrast between groups or another clearly specified comparison. A single-group study cannot by itself separate the contribution of the regimen from other influences on the observed outcome. This is why the registry's warning about the absence of a randomized comparison is important. No comparative treatment estimate is reported.
What do the planning assumptions mean?
The sample-size assumptions describe a planning illustration, not the trial's own design justification. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event calculations, the assumptions refer to the total number of events using Schoenfeld; for other outcomes, they refer to participants per arm. These are hypothetical planning conditions and do not turn this single-group trial into a two-arm trial.
General: A planning calculation asks what sample size might be needed under chosen assumptions. It is not an observed result and is not a measure of the probability that the trial's findings are correct. Sample-size illustrations based on an observed effect can be sensitive to the size and uncertainty of that effect. The registry record does not report its own sample-size justification, and the posted information does not include the underlying observed effect or numerical planning outputs. No planning figure can therefore be interpreted from the registry record.
What are hazard ratios and why are they absent from the interpretation?
General: A hazard ratio compares event rates over time between groups under a specified model. Its meaning depends on the analysis, the groups being compared, and the model assumptions. This record's methodological note says that only sponsor-reported hazard ratios are used, but no sponsor-reported hazard ratio is reported in the registry record. With a single listed group and no reported estimate, there is no hazard ratio to interpret. No proportional-hazards assumption or survival model is specified in the registry record.
The record lists 39 enrolled participants, while the adverse-event group lists 36 at risk. Those entries should not be treated as interchangeable analysis counts. The number analyzed for PFS, the handling of participants without evaluable follow-up, missing data procedures, and the analysis population are not reported in the registry record. The registry also lists zero analyses. These omissions limit assessment of how the planned endpoint was analyzed and how robust any estimate might be.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists progression-free survival as the primary outcome and identifies adverse events, overall survival, and objective response rate as secondary outcomes. It does not report a multiplicity strategy, such as whether any adjustment or hierarchy was used when interpreting multiple outcomes. It also does not report outcome-specific analysis details or numerical secondary results. Without such information, readers cannot determine how the trial treated the possibility of chance findings across several outcomes.
Missing-data methods are not reported in the registry record. The record does not specify how participants without a measurable response, without documented progression, or with incomplete follow-up were handled. It does not state the censoring rules for PFS, how missing assessments were addressed, or what analysis population was used. The listed timeframe of baseline to 24 months does not resolve those questions.
Enrollment is recorded as 39, while the safety group lists 36 at risk. The record does not explain the difference or provide a participant flow accounting for enrollment, treatment, follow-up, and analysis. Those counts should therefore be read in their respective contexts rather than assumed to describe the same analysis population.
The registry lists zero analyses and does not report a fuller statistical analysis plan, interim analysis plan, or sample-size justification. These omissions do not establish that no such procedures existed; they mean the details are not reported in the registry record. As a result, the extent to which the posted outcomes reflect prespecified analyses, how incomplete observations were handled, and how multiplicity was considered cannot be assessed from the record.
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 |
|---|---|---|---|
| Paclitaxel and Gemcitabine + Avastin | 25 | 36 | 69.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Paclitaxel and Gemcitabine + Avastin | 2 of 36 |
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 |
|---|---|
| Paclitaxel and Gemcitabine + Avastin | 36 of 36 |
Most frequent serious adverse event terms
| Event term | Organ system | Paclitaxel and Gemcitabine + Avastin |
|---|---|---|
| Neutropenia: Induction | Blood and lymphatic system disorders | 6 of 36 |
| Hypertension: end of induction | Cardiac disorders | 5 of 36 |
| Hypertension grade: maintenance | Cardiac disorders | 4 of 36 |
| Proteinuria: Induction | Renal and urinary disorders | 4 of 36 |
| Proteinuria: Maintenance | Renal and urinary disorders | 4 of 36 |
| Fatigue: Induction | General disorders | 1 of 36 |
| Nausea Vomiting: Induction | Gastrointestinal disorders | 1 of 36 |
| Hypertension Grade: end of Cycle 1 | Cardiac disorders | 1 of 36 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Paclitaxel and Gemcitabine + Avastin |
|---|---|---|
| Fatigue: Induction | General disorders | 32 of 36 |
| Hypertension grade: end of induction | Cardiac disorders | 32 of 36 |
| Anemia: Induction | Blood and lymphatic system disorders | 27 of 36 |
| Hypertension grade: end of Cycle 1 | Cardiac disorders | 26 of 36 |
| Diarrhea: Induction | Gastrointestinal disorders | 20 of 36 |
| Neuropathy: Induction | Nervous system disorders | 19 of 36 |
| Thrombocytopenia: Induction | Blood and lymphatic system disorders | 17 of 36 |
| Nausea/Vomiting: Induction | Gastrointestinal disorders | 17 of 36 |
| Hypertension grade: maintenance | Cardiac disorders | 17 of 36 |
| Neutropenia: Induction | Blood and lymphatic system disorders | 14 of 36 |
Serious events with the highest arm-level rate: neutropenia: induction (16.7%), hypertension: end of induction (13.9%), hypertension grade: maintenance (11.1%), proteinuria: induction (11.1%), proteinuria: maintenance (11.1%).
The adverse-event record lists one treatment group, Paclitaxel and Gemcitabine + Avastin. It reports 36 participants at risk for serious adverse events, with 25 affected; for other adverse events it lists 36 at risk and 36 affected. The record also lists 2 deaths. The relationship between the safety counts and the enrollment of 39 is not explained in the registry record.
The selected serious-event terms are reported with their own labels and percentages: Neutropenia: Induction, 16.7%; Hypertension: end of induction, 13.9%; Hypertension grade: maintenance, 11.1%; Proteinuria: Induction, 11.1%; Proteinuria: Maintenance, 11.1%; and Fatigue: Induction, 2.8%. These are the registry's listed terms and values. The record does not give further detail about event definitions, severity thresholds, duration, or whether categories overlap.
General: An adverse-event count describes events or affected participants as defined by the reporting system; it does not by itself establish that treatment caused an event. A single-group safety record also offers no direct comparison with another regimen. The registry does not state whether the 2 deaths were treatment-related, and causality should not be inferred from the count. The reported figures describe the listed safety observations, not a comparative risk estimate.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase II single-group study evaluated metronomic paclitaxel and gemcitabine with Avastin in participants with advanced non-squamous non-small cell lung cancer. It identifies PFS as the primary endpoint and describes how progression was defined. It also records enrollment of 39, the treatment schedule, selected adverse-event figures, and completion status.
The key limitation for interpreting the primary result is that the median PFS and its 95% confidence interval are not reported in the registry record. No sponsor-reported hazard ratio or other numerical PFS analysis estimate is reported. Consequently, the observed PFS magnitude, its precision, and the extent of follow-up cannot be described from these registry entries. A defined endpoint is not itself evidence of a particular outcome.
The study has no separate comparator group. Therefore, even if a treatment-group outcome were available, this design would not provide a randomized comparison against another treatment. The record cannot establish how the regimen compares with an alternative or determine what portion of any observed outcome is attributable to the treatment rather than other influences. The trial's title or rationale should not be read as a substitute for comparative outcome data.
The safety entries are likewise descriptive. They report serious and other adverse-event counts, selected serious-event terms, and deaths, but do not provide a comparison group or establish causality. The registry does not report whether the deaths were related to treatment. The difference between enrollment and the safety group count is not explained, so the populations represented by those entries cannot be reconciled from the record.
General: Statistical interpretation depends on matching conclusions to the design, outcome definition, and available estimates. A result may be statistically uncertain even when a point estimate is available, and design limitations can remain even when an estimate is precise. Here, the primary numerical estimate is absent and the design is non-comparative. The defensible reading is therefore limited to what the record describes about study conduct and safety reporting, while the numerical PFS result and comparative effect remain unknown in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates why design information and outcome reporting need to be read together. The registry gives a clear primary endpoint definition and identifies a time-to-event summary, but it does not report the median PFS or its 95% confidence interval. Readers can understand what the investigators intended to measure without being able to assess the measured outcome. The distinction between an endpoint definition and a reported result is central to statistical interpretation.
The single-group design is also statistically important. It supports description of the treated group but does not provide a randomized control contrast. A treatment effect is inherently comparative: it depends on how outcomes under one strategy differ from outcomes under another. Without a second group, the record cannot separate treatment effects from other explanations for the observed course. The registry itself flags the absence of a randomized comparison.
The record also shows why denominators and analysis populations matter. It lists 39 enrolled participants and 36 at risk in the adverse-event group, without explaining the relationship. That leaves uncertainty about who contributed to the safety counts and whether the same group contributed to other outcomes. Clear participant flow and outcome-specific analysis counts would help readers evaluate completeness.
Finally, the planning assumptions should not be confused with observed evidence. A hypothetical sample-size illustration depends on chosen assumptions, including an effect to detect and a statistical model. It is not a result from the trial, nor does it show that the study had a particular probability of detecting an effect. The registry does not report its own sample-size justification or numerical planning outputs. These distinctions help keep design intentions, observed data, and statistical conclusions separate.
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 details needed for a fuller assessment are not reported in the registry record. The primary endpoint estimate and its 95% confidence interval are absent, as are numerical results for the listed secondary outcomes. No sponsor-reported hazard ratio or detailed endpoint analysis is reported. As a result, the PFS outcome cannot be assessed for magnitude or precision.
The record describes progression using RECIST v1.0 but does not state how deaths without documented progression were treated, what censoring rules were used, or how missing assessments and incomplete follow-up were handled. It also does not identify the PFS analysis population or participant count. The stated timeframe of baseline to 24 months does not supply those methodological details.
The study is single group, with allocation listed as NA and masking as none. There is no concurrent comparison group in the record, limiting comparative interpretation. Enrollment is listed as 39, while the adverse-event group lists 36 at risk; the record does not explain this difference. The truncated treatment description ends after “unless,” leaving the condition for the stated total of 6 cycles unreported in the registry record.
The registry does not report a sample-size justification, interim analysis plan, multiplicity procedure, or fuller statistical analysis plan. It lists zero analyses. It also does not state whether the 2 reported deaths were treatment-related or explain further details of event ascertainment. These gaps limit evaluation of analysis choices, participant accounting, and causal interpretation of safety findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lower Dose Chemotherapy Given More Frequent With Avastin to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer — NCT00655850.
- Registry record last updated 2017-07-17; status last verified 2017-06.
- Results first posted 2017-05-24.
- 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
NCT00655850 is recorded as a completed Phase II, single-group study sponsored by the University of Alabama at Birmingham. The registry lists enrollment of 39, allocation as NA, and no masking. The study evaluated metronomic paclitaxel and gemcitabine with Avastin in advanced non-squamous non-small cell lung cancer.
The primary endpoint is PFS, defined from treatment start to disease progression under RECIST v1.0, with a median and 95% confidence interval specified for a baseline-to-24-month timeframe. The median and interval are not reported in the registry record. Secondary outcomes include adverse events, overall survival, and objective response rate; numerical results are not reported in the registry record.
The safety record lists 25 participants with serious adverse events among 36 at risk, 36 with other adverse events among 36 at risk, and 2 deaths. The record does not provide a randomized comparator or explain the relationship between enrollment and the safety group count.