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 Cabozantinib in Advanced Solid Malignancies (NCT01588821), a na phase 2 study. The primary outcome is Number of Participants With Bone Bio-marker Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01588821 |
| Phase | Phase 2 |
| Condition | Lung Cancer, Solid Tumor (Not Breast or Prostate Cancers) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 37 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced solid malignancies and bony metastases were the population of interest. The official title excludes breast and prostate malignancies, and the listed conditions include lung cancer and solid tumors other than breast or prostate cancer. The registry record says 19 participants were evaluable for the bone-biomarker response endpoint. The specific eligibility criteria and the characteristics of enrolled participants are not reported in the registry record.
Intervention
The intervention was cabozantinib, described in the registry record as an investigational drug. The record outlines the study rationale as investigating its potential activity in cancer that has spread to bone. Dose, schedule, treatment duration and rules for changing or stopping treatment are not reported in the registry record.
Comparator
There was no concurrent comparison group. The study is listed as single-group, with allocation recorded as not applicable and no masking. Consequently, the registry record does not set up a direct comparison with placebo, usual care or another treatment. Results from this study cannot by themselves separate a treatment-associated change from changes that might occur for other reasons.
Primary question
The primary question was how many participants had a bone-biomarker response at 8 weeks. A participant counted as a responder if a bone biomarker concentration decreased by at least 40%. The biomarkers of interest were serum C-terminal telopeptide, urine N-terminal telopeptide and serum N-terminal telopeptide. The response count and its uncertainty are not reported in the registry record, so the primary question cannot be answered from the posted results summarized in the record.
3. Trial Design
This was a Phase II clinical trial of cabozantinib in people with advanced solid malignancies and bony metastases. The registry lists a single treatment arm, described as cabozantinib, and identifies the study model as single-group. Allocation is not applicable, and masking is listed as none. These features mean that participants were not assigned between competing study arms in a randomized comparison, and the study did not use blinding as recorded in the registry.
The registry lists enrollment of 37 participants and status as completed. The listed study start is 2012-06, and primary completion is recorded as 2017-01. The sponsor is Massachusetts General Hospital. The official title specifies non-breast and non-prostate advanced solid malignancies with bony metastases; the conditions listed include lung cancer and solid tumor excluding breast or prostate cancer.
The primary outcome was a count of participants with a bone-biomarker response, assessed at 8 weeks. The registry description defines response as at least a 40% decrease in biomarker concentration. It also says that only 19 participants were evaluable for determining response by bone biomarkers. Why some enrolled participants were not evaluable, and how missing biomarker measurements were handled, are not reported in the registry record.
Secondary outcomes include skeletal-related events, quality of life assessed by FACT-G, overall tumor response rate, MET amplification in tumor samples, response in bone metastatic disease and time to a skeletal-related event. The record lists seven outcome measures overall, but does not report a result for the primary endpoint or an analysis for it. Without a control group, any observed change would be a within-group description rather than a randomized estimate of a difference between treatments.
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 | Cabozantinib |
|---|---|
| STARTED | 37 |
| COMPLETED | 37 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Only 19 participants were evaluable for determination of response by bone bio-markers
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 | Cabozantinib |
|---|---|---|
| Participants analysed | 37 | |
| Age, Continuous | years | 54.4 (18 to 83) |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 23 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: United States | participants | 37 |
| Diagnosis: Sarcoma | Participants | 14 |
| Diagnosis: Renal Cell Carcinoma | Participants | 7 |
| Diagnosis: Non-Small cell lung cancer | Participants | 5 |
| Diagnosis: Head and neck carcinoma | Participants | 4 |
| Diagnosis: Thyroid Cancer | Participants | 2 |
| Diagnosis: Melanoma | Participants | 2 |
| Diagnosis: Adenoid Cystic Carcinoma | Participants | 1 |
| Diagnosis: Metastatic chondroblastoma | Participants | 1 |
| Diagnosis: Chordoma | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Bone Bio-marker Response, measured over 8 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants meeting a prespecified bone-biomarker response definition at 8 weeks. The registry identifies biomarkers related to osteoblast and osteoclast activity: serum C-terminal telopeptide, urine N-terminal telopeptide and serum N-terminal telopeptide. A response required at least a 40% decrease in biomarker concentration. The record does not clarify whether response on any one biomarker was sufficient, how results across biomarkers were combined, or how participants with incomplete measurements were classified.
Bone biomarkers can provide a measurable biological indicator of activity in bone, which is relevant to a study focused on cancer with bony metastases. A threshold-based endpoint turns a continuous laboratory measurement into a responder count. That can make the endpoint easier to summarize, but it discards information about the size and pattern of changes that do not meet the threshold. The endpoint is a biomarker response, not itself a direct measure of symptoms, skeletal complications, tumor shrinkage or survival.
The registry reports that 19 participants were evaluable for this endpoint, but the number meeting the response definition is not reported in the registry record. The posted information therefore does not establish the observed response frequency or its precision. The endpoint definition also does not by itself demonstrate that a biomarker change predicts a clinical benefit.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed Phase II, single-group study with 37 enrolled participants and a primary bone-biomarker assessment at 8 weeks. It states that 19 participants were evaluable for determining response. However, it does not report how many met the response criterion, the biomarker measurements, or an uncertainty interval for the primary outcome. The main efficacy question therefore remains unanswered in the registry record.
The endpoint was based on a threshold: at least a 40% decrease in a specified biomarker concentration. A threshold defines who is classified as a responder, but interpretation requires the observed responder count and a clear account of how results across the listed biomarkers were combined. Neither the primary response count nor that combination rule is reported in the registry record. The endpoint description alone is not evidence that participants did or did not respond.
The study had no concurrent control arm. A single-group result, if available, would describe what was observed among participants receiving cabozantinib; it would not directly estimate what would have happened to comparable participants under another treatment or without the study treatment. In general, a control group helps distinguish treatment-associated outcomes from changes related to disease course, other care or selection of participants. This design cannot make that comparison.
The registry lists several secondary outcomes, including skeletal-related events, quality of life, tumor response, MET amplification and time to a skeletal-related event. The outcome names indicate areas of interest, but do not supply estimates or conclusions. The number of analyses is recorded as zero; the registry record does not explain the absence of analyses or provide statistical results for these outcomes. No conclusion about their results should be inferred from their listing.
Safety information is reported separately from the primary biomarker endpoint. The adverse-event record lists 9 participants affected by serious adverse events among 37 at risk, and 4 deaths. It also lists serious-event terms with a frequency of 2.7% each. These are descriptive safety entries; the record does not establish whether events were caused by cabozantinib, nor does it provide a comparison group for estimating excess risk.
Overall, the posted information describes the study question, design and endpoint definition, but does not provide the primary outcome result needed to quantify biomarker response. The completed status does not substitute for outcome data. The record supports describing what the study set out to assess and the limitations of its design, not a conclusion about the treatment's effectiveness.
9. Statistical Methods Explained
What does a single-group design estimate?
A single-group study observes outcomes among participants receiving the study intervention without a concurrent comparison arm. Its direct statistical summaries can describe counts, proportions or measurement changes within that group. They do not, on their own, estimate a causal difference between treatments. In general, a randomized comparison is useful because allocation can reduce systematic differences between groups, while a control group also helps account for outcome changes that might occur without the intervention.
This study is recorded as single-group, with allocation not applicable and masking none. Thus, it is not appropriate to interpret the study as a like-for-like treatment comparison. The registry itself flags that it is not a randomized comparison. The absence of a control group is especially important when interpreting changes over time: a before-and-after pattern cannot tell whether the same pattern would have occurred under another approach.
How should a responder endpoint be understood?
The primary outcome is a count of participants who met a binary response definition. Although biomarker concentrations are measurements, the registry classifies the primary endpoint as binary because each evaluable participant is categorized as a responder or not based on a threshold. A count is informative only when the number assessed and the response rule are clear. Here, the record reports 19 evaluable participants and defines response as at least a 40% decrease, but it does not report the number who responded.
In general, a confidence interval describes the range of estimates reasonably compatible with the observed data under a statistical model. It conveys precision as well as the point estimate. A response count without an interval can be difficult to interpret, particularly when the number assessed is limited. No confidence interval or other uncertainty measure for the primary response is reported in the registry record.
Thresholding has trade-offs. It creates an interpretable classification, but two participants with similar biomarker changes on opposite sides of the cutoff may be categorized differently, while changes of different magnitudes on the same side receive the same classification. Continuous biomarker results could retain more detail, but the registry record does not report those values or a continuous-outcome analysis.
Why do analysis populations matter?
The enrolled population and the population evaluated for a particular outcome need not be identical. The record lists enrollment of 37 and says 19 were evaluable for the primary biomarker response. That difference makes it important to know the analysis population, the reasons measurements were unavailable and the handling of missing values. Those details are not reported in the registry record. It is therefore not possible to determine whether the evaluable participants differed from participants without an evaluable response, or how such differences might affect interpretation.
In general, analyzing only participants with available measurements can produce a biased estimate if availability is related to outcome or participant characteristics. Other approaches may use assumptions about missing outcomes, but those assumptions must be stated and assessed. The registry record does not describe a missing-data method for this endpoint, so no such method should be presumed.
What does the planning framework say?
The registry describes planning illustrations based on a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect expressed as a fraction of the observed effect. It specifies that time-to-event illustrations concern a total number of events, while other illustrations concern participants per arm. These are planning assumptions, not a description of the actual trial design, which is single-group.
In general, a sample-size calculation asks how much information a hypothetical study might need to detect a specified effect under stated assumptions. Such a calculation is not observed power and does not establish what the trial found. The record does not report the numerical planning results or enough observed primary outcome information to interpret an effect-based illustration. The planning framework should therefore not be read as evidence of a measured response or as a reconstruction of the trial's original design justification. The trial's own sample-size justification is not reported in the registry record.
How should multiplicity and safety summaries be read?
When a study evaluates several outcomes or conducts several analyses, the chance of at least one apparently notable result can increase if many tests are considered. Statistical methods may address this through prespecified outcome hierarchy or adjustments, but these choices are not described in the registry record. It lists multiple secondary outcomes, while the number of analyses is recorded as zero. No multiplicity strategy or inferential results are reported.
Safety entries are descriptive counts and listed event terms, not a treatment-effect analysis. General principles of event reporting require attention to the denominator, event definition, overlap between participants and events, and the observation period. The record does not report enough detail to determine whether listed serious-event terms overlap, their timing, or their relationship to treatment. The listed frequencies should not be added together to estimate a total.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary biomarker-response endpoint and several secondary outcomes: skeletal-related events, FACT-G quality of life, overall tumor response, MET amplification, response in bone metastatic disease and time to a skeletal-related event. Considering multiple outcomes can create multiplicity: the more statistical questions examined, the greater the chance of a seemingly notable finding arising by chance when each is interpreted separately. In general, a prespecified hierarchy or adjustment can help manage this issue. Such a hierarchy or adjustment is not reported in the registry record.
The record lists zero analyses and provides no statistical results for the primary or secondary outcomes. It does not explain the absence of analyses, and it is not possible to establish whether analyses were conducted but not entered in the registry. No inference should be drawn from the outcome list alone.
For the primary endpoint, the record reports that 19 participants were evaluable, while enrollment was 37. Reasons for the difference, definitions of the evaluable population, missing measurement patterns and any imputation or sensitivity analyses are not reported in the registry record. In general, missing-data handling matters because results among participants with available measurements may not represent the full enrolled population if availability is related to outcomes or participant characteristics. The available record does not permit assessment of that possibility.
The record also does not report a statistical analysis plan, the method used to combine the listed biomarkers, or a strategy for handling multiple endpoints. These omissions limit reproducibility and make it difficult to assess whether the endpoint and analysis choices were prespecified. They do not establish that a particular method was or was not used outside the registry 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 |
|---|---|---|---|
| Cabozantinib | 9 | 37 | 24.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cabozantinib | 4 of 37 |
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 |
|---|---|
| Cabozantinib | 37 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | Cabozantinib |
|---|---|---|
| Fatigue | General disorders | 1 of 37 |
| Pain | General disorders | 1 of 37 |
| Abdominal pain | Gastrointestinal disorders | 1 of 37 |
| Diarrhea | Gastrointestinal disorders | 1 of 37 |
| Nausea | Gastrointestinal disorders | 1 of 37 |
| Cholecystitis | Hepatobiliary disorders | 1 of 37 |
| Allergic reaction | Immune system disorders | 1 of 37 |
| Abdominal infection | Infections and infestations | 1 of 37 |
| Lung infection | Infections and infestations | 1 of 37 |
| Meningitis | Infections and infestations | 1 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cabozantinib |
|---|---|---|
| Fatigue | General disorders | 24 of 37 |
| Hypertension | Vascular disorders | 23 of 37 |
| Constipation | Gastrointestinal disorders | 21 of 37 |
| Aspartate aminotransferase increased | Investigations | 19 of 37 |
| Diarrhea | Gastrointestinal disorders | 18 of 37 |
| Pain | General disorders | 17 of 37 |
| Nausea | Gastrointestinal disorders | 17 of 37 |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | 13 of 37 |
| Alanine aminotransferase increased | Investigations | 13 of 37 |
| Surgical and medical procedures - Other, specify | Surgical and medical procedures | 13 of 37 |
Serious events with the highest arm-level rate: fatigue (2.7%), pain (2.7%), abdominal pain (2.7%), diarrhea (2.7%), nausea (2.7%).
The adverse-event summary lists 37 participants at risk for serious adverse events and 9 affected. It lists 37 at risk for other adverse events and 37 affected, and records 4 deaths. The registry also lists serious adverse event terms with a frequency of 2.7% each: fatigue, pain, abdominal pain, diarrhea, nausea and cholecystitis. These are descriptive entries and should be read in the context of the registry's event definitions and reporting period, details that are not reported in the registry record.
The event terms may not represent separate participants. The record does not say whether an individual could contribute to more than one term, so the listed frequencies should not be added together. Nor does the record specify the timing, duration, severity grading or investigator assessment of causality for each event. A serious adverse event is not necessarily caused by the intervention; the record does not provide a basis for assigning causation.
The deaths are reported as a count, but the registry record does not give causes or indicate their relationship to treatment. With no concurrent control group, the entries do not estimate how safety outcomes compare with another treatment. The figures describe reported events in the study, not comparative risks or individualized predictions.
12. What the Result Does, and Does Not, Mean
The study addressed whether cabozantinib was associated with a bone-biomarker response in people with advanced solid malignancies and bony metastases. The registry defines a response at 8 weeks as at least a 40% decrease in biomarker concentration and states that 19 participants were evaluable. However, the number who met the response definition is not reported in the registry record. The primary efficacy result therefore cannot be quantified from the posted information.
The design also limits what a result could establish. Because the study had a single treatment group and no randomized control arm, an observed change would describe outcomes in that group, not the difference caused by cabozantinib compared with another treatment or no treatment. A single-group result cannot rule out other explanations for change over time.
The biomarker endpoint is not equivalent to a clinical outcome. The registry includes other outcomes related to quality of life, tumor response and skeletal events, but does not report their results in the record. A biomarker response, even if it were reported, would not alone show improvement in symptoms or prevention of clinical events.
The safety entries record serious adverse events, other adverse events and deaths, but do not establish causation or comparative risk. Interpretation is further constrained by missing information about analysis populations, incomplete measurements, endpoint combination rules and statistical methods. These are limitations of what can be concluded from the registry record; they do not prove that additional data or analyses do not exist elsewhere.
Accordingly, the registry supports a description of the study design and intended endpoint, but not a conclusion about the size, precision or clinical meaning of a treatment effect. Completed status indicates the study is recorded as completed; it does not provide the missing outcome estimate.
13. Why This Trial Matters Statistically
This study raises an important statistical distinction between measuring biological activity and estimating a treatment effect. Its primary endpoint uses a thresholded biomarker response, which can be counted among evaluable participants. But a responder count is interpretable only when the numerator, analysis population and uncertainty are available. The registry reports the evaluable population but not the response count, so the central statistical quantity is missing from the record.
The single-group design is another central consideration. It can describe observations in participants receiving cabozantinib, but it does not provide a concurrent benchmark. Without that comparison, changes cannot be attributed to the intervention with the same basis as a randomized treatment contrast. This matters in oncology research, where disease course, other care and participant selection may also affect observed outcomes.
The distinction between enrolled and evaluable populations also matters. The record gives both enrollment and the number evaluable for biomarkers, but does not explain the difference or describe missing-data handling. Transparent reporting of who contributed to each endpoint helps readers judge whether the analyzed group represents the intended population.
Finally, the registry lists multiple secondary outcomes without reporting analysis results or a multiplicity strategy. Statistical interpretation depends not only on endpoint definitions, but also on how many questions were examined and which analyses were planned. The record illustrates why a completed status, a clearly stated endpoint and safety counts are not substitutes for complete outcome reporting, uncertainty estimates and a transparent analysis plan.
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 primary limitation is that the registry record does not report the number of participants who met the bone-biomarker response definition, nor an estimate of uncertainty. Although 19 participants were evaluable, the response outcome cannot be reconstructed from the available record. Biomarker values and the rule for combining results across the listed biomarkers are also not reported.
The study was single-group and unmasked, with no randomized comparator. As a result, the design does not support a direct estimate of a treatment difference. The record does not report eligibility details, participant characteristics, treatment dose or schedule, or reasons participants were not evaluable for the primary endpoint. These gaps limit assessment of who contributed to the endpoint and how broadly the findings might apply.
Missing-data methods, endpoint-specific analysis populations, statistical methods and a multiplicity strategy are not reported in the registry record. The record lists secondary outcomes but does not provide their results. For safety, it gives counts and event terms without reporting event timing, severity detail, causality assessments or causes of death. The listed serious-event frequencies may overlap across participants, and the record does not clarify that overlap.
These limitations describe the information available in the registry record. They do not establish whether additional analyses, protocol details or results are available elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Cabozantinib in Advanced Solid Malignancies — NCT01588821.
- Registry record last updated 2020-09-29; status last verified 2020-09.
- Results first posted 2018-01-10.
- 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
NCT01588821 is a completed Phase II, single-group study of cabozantinib in advanced solid malignancies with bony metastases. The registry lists enrollment of 37 and identifies Massachusetts General Hospital as sponsor. The primary endpoint was the number of participants with a bone-biomarker response at 8 weeks, defined as at least a 40% decrease in biomarker concentration. The record states that 19 participants were evaluable for this outcome, but does not report the response count or an analysis.
There was no randomized comparator, and masking is listed as none. Secondary outcomes include skeletal-related events, quality of life, tumor response, MET amplification and time to a skeletal-related event. The registry also reports adverse-event counts and serious-event terms, without enough detail to establish causality or comparative risk. The primary result, analysis methods, missing-data handling and multiplicity approach are not reported in the registry record.