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 Ridaforolimus With Cetuximab: Adv Non-Small Cell Lung, Colorectal, Head & Neck Cancer (NCT01212627), a na phase 1 study. The primary outcome is Determine Maximum Tolerated Dose (MTD) of Ridaforolimus With Given With Cetuximab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01212627 |
| Phase | Phase 1 |
| Condition | Non-Small Cell Lung Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Angela Taber MD |
| Results posted | Yes |
2. Clinical Question
Population
The registry summary describes people with advanced head and neck, lung, or colon cancer that progressed after initial therapy. The condition field lists non-small cell lung cancer, so the condition listing and the broader population in the summary are not fully aligned. The planned enrollment was 12.
Intervention
The study concerns ridaforolimus given with cetuximab. The arm description specifies ridaforolimus at 20mg daily, 5 days each week, on a 28 day cycle until progression. Although cetuximab is named in the study title and purpose, its dosing and administration details are not reported in the registry record.
Comparator
No separate comparator is described. The registry classifies the study as single group and its allocation as NA. Participants therefore were not assigned to a posted control treatment for a like-for-like comparison.
Primary question
The primary objective is to determine the maximum tolerated dose of ridaforolimus given with cetuximab. The registry also describes assessing safety and side effects, and gives preliminary information on the combination in advanced head and neck cancer as a secondary purpose. It does not report a primary endpoint result or a treatment-effect estimate.
In statistical terms, the primary question is about dose finding and tolerability, rather than an estimate of comparative efficacy. The record lists dose levels of 20 mg/day, 30 mg/day, and 40 mg/day, with dose-limiting toxicities evaluated after the first 3 patients have received 1 cycle. It says the next level begins if everything is ok, but does not report the complete decision rules. The registry record also does not give observed dose-limiting toxicity results or identify a maximum tolerated dose. The preliminary treatment question therefore remains distinct from the stated primary dose-finding question, and no answer to either question can be inferred from the posted endpoint data.
3. Trial Design
This is a phase I, single-group study with planned enrollment of 12. The registry lists allocation as NA and masking as none. It is marked terminated. The recorded start is 2010-09 and primary completion is 2012-12. The registry does not report why the study was terminated or whether planned enrollment was achieved.
The study title, official title, and summary describe ridaforolimus in combination with cetuximab in advanced head and neck cancer, non-small cell lung cancer, and colon cancer. The condition field, however, lists non-small cell lung cancer only. The summary says the cancers had progressed after initial therapy. The registry record does not provide further eligibility details, baseline participant characteristics, or how many participants had each cancer type.
The listed intervention and arm description focus on ridaforolimus. The arm description specifies 20mg daily, 5 days each week, in a 28 day cycle until progression. The primary endpoint description also lists dose levels of 20 mg/day, 30 mg/day, and 40 mg/day, calling these “Weekly Ridaforolimus Dose Level” values. These descriptions are not fully aligned in their wording, and the registry does not clarify the schedule for each level. Cetuximab is part of the stated combination, but its dose and schedule are not reported in the registry record.
The record describes testing after the first 3 patients have enrolled and received 1 cycle, followed by evaluation of dose-limiting toxicities. It says that if everything is ok, the next medication level begins. Further escalation and stopping rules, cohort assignment details, and criteria for dose-limiting toxicity are not reported. The registry record does not provide a randomized comparison, a masking procedure, or a control group. Thus, the design supports describing dose-finding procedures and observed safety within the treated group, but not a controlled estimate of the combination’s effect.
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 | Ridaforolimus, |
|---|---|
| STARTED | 12 |
| COMPLETED | 12 |
| 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 | Ridaforolimus, |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 |
| Age, Categorical: >=65 years | Participants | 3 |
| Age, Continuous | years | 57.8 (42 to 69) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 8 |
| Region of Enrollment: United States | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Determine Maximum Tolerated Dose (MTD) of Ridaforolimus With Given With Cetuximab, measured over 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/day |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of ridaforolimus given with cetuximab, recorded as a number with the unit mg/day and a timeframe of 1 year. The registry’s description focuses on dose escalation and the evaluation of dose-limiting toxicities. It lists dose levels of 20 mg/day, 30 mg/day, and 40 mg/day, and says the first testing occurs after the first 3 patients are enrolled and have received 1 cycle. The next level is to begin if everything is ok.
In general, a maximum tolerated dose endpoint is used in early dose-finding research to identify a dose level considered tolerable under specified toxicity rules. That makes it a different kind of endpoint from a comparison of tumor response or survival between treatments. The registry record does not define the toxicity window, the precise criteria for a dose-limiting toxicity, or the full dose-escalation decision algorithm. It also does not report a numerical maximum tolerated dose, dose-limiting toxicity counts by level, or a primary endpoint analysis. The endpoint’s intended role is clear, but the posted information is insufficient to reproduce how the endpoint would be determined or to state the resulting dose.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted information establishes the study’s aims and basic design, not an estimate of treatment benefit. It is a phase I, single-group study of ridaforolimus with cetuximab, planned for 12 participants and marked terminated. Its primary objective is dose finding: determining the maximum tolerated dose of ridaforolimus with cetuximab. The record does not post a value for that endpoint, dose-limiting toxicity counts by dose level, or a primary analysis. No result about the maximum tolerated dose can therefore be stated from the registry entry.
The registry describes dose levels of 20 mg/day, 30 mg/day, and 40 mg/day and a toxicity review after the first 3 patients have received 1 cycle. It does not provide the detailed toxicity definition or all rules governing escalation and stopping. The dose schedule is also described differently in separate fields: the arm description gives 20mg daily, 5 days each week, on a 28 day cycle, whereas the endpoint description labels the levels “Weekly Ridaforolimus Dose Level.” The record does not explain this wording. These limits matter because dose-finding interpretation depends on the exposure schedule and the rules used to classify and respond to toxicities.
The record’s safety information lists 12 participants at risk for serious adverse events, with 4 affected, and 12 at risk for other adverse events, with 12 affected. The listed serious terms—acute renal failure, anemia, aspiration, ejection fraction, hypokalemia, and pericardial effusion—each have a reported percentage of 8.3%. These data describe events recorded for the study group; without a comparator, they do not estimate whether the combination changes risk relative to another treatment. The record does not report deaths in the field used for deaths, so that value must not be interpreted as zero.
No inferential analyses are listed, and the record does not post an efficacy estimate, confidence interval, or p-value. The summary mentions preliminary information about whether the combination is helpful in advanced head and neck cancer, but the posted outcome information does not supply a result addressing that aim. The record also does not provide cancer-specific outcome results or participant-level results. In general, an estimate is more informative when its uncertainty and analysis population are reported; those details are not available in this registry entry. Consequently, the available information supports a cautious description of design and recorded safety counts, but not a comparative efficacy conclusion or a precise assessment of the primary endpoint.
9. Statistical Methods Explained
The design is single group, with allocation listed as NA and masking listed as none. There is no separate control arm in the registry record. In general, a single-group study can describe outcomes among enrolled participants, but it cannot by itself separate a treatment-associated outcome from the course that might have occurred without the study treatment. A randomized comparison is not reported, so any treatment-effect contrast against usual care or another regimen is unavailable.
What does the primary endpoint measure?
The primary endpoint is the maximum tolerated dose of ridaforolimus with cetuximab, expressed in mg/day, with a timeframe of 1 year. The description lists 20 mg/day, 30 mg/day, and 40 mg/day dose levels and says that dose-limiting toxicities are evaluated once the first 3 patients are enrolled and have received 1 cycle. It says the next level begins if everything is ok. The precise toxicity criteria, full escalation and stopping rules, and handling of participants who do not complete a cycle are not reported in the registry record. Those details are important because the endpoint is determined by a sequence of toxicity observations and dose decisions, not simply by comparing an average outcome across groups.
The arm description gives a ridaforolimus schedule of 20mg daily, 5 days each week, on a 28 day cycle until progression. The endpoint description labels the dose levels “Weekly Ridaforolimus Dose Level.” The registry does not explain the difference in wording or give a complete schedule for each listed level. It lists cetuximab as part of the combination’s title and purpose, but does not give cetuximab dosing details. Thus, the intended combination and the general dose-finding aim are recorded, while important operational details are not.
How should uncertainty and analyses be read?
In general, a confidence interval describes the range of values compatible with an estimate under the statistical model used. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone establishes clinical importance. No confidence interval or inferential analysis is reported for the primary endpoint in this record. The count of analyses is listed as 0. It is therefore not possible to assess statistical uncertainty around an estimated maximum tolerated dose or any efficacy outcome from the posted results.
The study’s principal question is dose selection and tolerability, not a comparative hypothesis test. In general, dose-finding decisions are governed by prespecified toxicity definitions and escalation rules. The registry gives a brief description of an initial review and a conditional move to the next level, but not enough detail to reconstruct the decision algorithm. A reader should not assume that a particular standard design, model, or escalation rule was used; such a method is not reported in the registry record.
The sample-size planning illustration associated with the posted material is described as a calculation from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it describes the effect to detect as a stated fraction of the observed effect. The illustration says non-time-to-event quantities are expressed as participants per arm for a specified power, while time-to-event calculations use total events. These assumptions do not describe this trial’s single-group design, which has no two-arm comparison, and the registry record provides no observed effect estimate for this study. Any such illustration is a planning exercise rather than evidence of the study’s achieved power. It cannot supply a missing treatment-effect estimate or replace the study’s dose-finding analysis.
In general, over-dispersion means that observed variability exceeds what a statistical model assumes; ignoring it can make uncertainty appear too small. The registry does not report a model or outcome distribution for which over-dispersion was assessed. No claim about its presence or handling is warranted. Similarly, the record does not describe an interim efficacy analysis, covariate adjustment, subgroup modeling, or a multiplicity procedure. Their use is not reported in the registry record.
What can the posted counts establish?
The adverse-event figures are descriptive counts for the recorded group. They do not include a control-group rate, a modeled risk difference, or an uncertainty interval. In general, a count describes the events observed in the participants represented by its denominator, while a comparative effect requires appropriate data from comparison groups and an analysis plan. The event counts therefore should not be treated as evidence that the regimen caused or prevented an event, nor as a comparative estimate.
Overall, the methods information supports a limited account of the planned dose levels and initial toxicity review. It does not reveal the full analysis plan, all endpoint definitions, or the completed statistical analysis. These missing details limit reproducibility and make it inappropriate to infer more than the registry actually reports.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary dose-finding endpoint and a secondary outcome concerning tolerability and maximum tolerated dose across several dosing schedules. The summary also describes a preliminary purpose of gaining information about whether the combination is helpful in advanced head and neck cancer. The record does not explain how these aims were ordered for formal statistical testing, whether any outcomes were designated for confirmatory inference, or whether multiplicity was addressed. A multiplicity adjustment or testing hierarchy is not reported in the registry record.
The count of analyses is 0. The registry does not post a primary endpoint analysis, efficacy analysis, confidence interval, or p-value. It does not state whether analyses were planned by cancer type, dose level, or another subgroup. Such subgroup analyses, and any method for handling repeated looks at accumulating data, are not reported in the registry record. The brief description of evaluating toxicity after the first 3 patients have received 1 cycle does not establish that formal interim analyses were planned; the full monitoring and decision rules are not reported.
Missing-data handling is also not described. The record does not state how participants who withdrew, stopped treatment, missed assessments, or had incomplete toxicity follow-up were handled. An analysis population—such as a defined safety or dose-evaluable population—is not reported in the registry record, nor does the entry provide exclusions from analysis or reasons for any exclusions.
These omissions do not establish that the study had no analysis plan or that missing data occurred. They mean only that the registry record does not report those details. Without definitions of the analysis population, endpoint assessments, missing-data rules, and multiplicity approach, readers cannot independently reproduce an analysis or determine how robust an inferential result would be. In this record, no inferential result is posted for evaluation.
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 |
|---|---|---|---|
| Ridaforolimus, | 4 | 12 | 33.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ridaforolimus, | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Ridaforolimus, |
|---|---|---|
| acute renal failure | Investigations | 1 of 12 |
| Anemia | Investigations | 1 of 12 |
| aspiration | Investigations | 1 of 12 |
| ejection fraction | Investigations | 1 of 12 |
| Hypokalemia | Investigations | 1 of 12 |
| pericardial effusion | Investigations | 1 of 12 |
| Pleural Effusion | Investigations | 1 of 12 |
| pneumonia | Investigations | 1 of 12 |
| Respiratory Failure | Investigations | 1 of 12 |
| Shortness of Breath/dyspnea | Investigations | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ridaforolimus, |
|---|---|---|
| Anemia | Investigations | 10 of 12 |
| Dry skin/pruritis/cracked skin | Investigations | 8 of 12 |
| hypoalbuminemia | Investigations | 8 of 12 |
| Rash | Investigations | 8 of 12 |
| Fatigue | Investigations | 7 of 12 |
| Mucositis | Investigations | 7 of 12 |
| Nausea | Investigations | 7 of 12 |
| Hyponatremia | Investigations | 6 of 12 |
| hypocalcemia | Investigations | 6 of 12 |
| Hypomagnesemia | Investigations | 6 of 12 |
Serious events with the highest arm-level rate: acute renal failure (8.3%), anemia (8.3%), aspiration (8.3%), ejection fraction (8.3%), hypokalemia (8.3%).
The registry reports 12 participants at risk for serious adverse events and 4 affected. For other adverse events, it reports 12 at risk and 12 affected. These are counts for the study group, not comparisons against another treatment. The record does not give further definitions for how events were attributed, grouped, or assessed over time.
The listed serious adverse event terms are acute renal failure, anemia, aspiration, ejection fraction, hypokalemia, and pericardial effusion. Each term is accompanied by 8.3%. The entry does not provide event counts beside each term or explain whether participants could contribute to more than one term. A percentage by term should therefore be read as a registry-reported frequency, not as a distinct number of affected participants inferred from a calculation.
The deaths field is null, which means a death count is not reported in the registry record; it should not be read as zero deaths. The record also does not provide a comparator, exposure-adjusted rates, detailed severity or timing, or a causal assessment for the listed events. In general, adverse-event counts describe what was recorded during a study and do not by themselves establish that treatment caused an event. These limitations are particularly relevant when interpreting a small, single-group study.
12. What the Result Does, and Does Not, Mean
The record identifies a phase I study of ridaforolimus with cetuximab, planned for 12 participants, with dose finding and safety as its principal focus. It gives a brief description of dose levels and an initial toxicity review. The posted information also includes adverse-event counts for the study group. These registry entries support describing the study’s purpose and the events recorded, but do not establish a comparative treatment effect.
The primary endpoint is the maximum tolerated dose of ridaforolimus with cetuximab. A numerical endpoint result is not reported in the registry record. The record does not give dose-limiting toxicity results by level, the full dose-escalation rules, or the precise criteria used to classify toxicities. The planned dose levels should not be mistaken for a result identifying a tolerated dose.
The registry summary includes a preliminary question about whether the combination may be helpful in advanced head and neck cancer, but it does not report an efficacy result addressing that question. There is no posted comparator, treatment-effect estimate, confidence interval, or inferential analysis. The study’s single-group design cannot provide a like-for-like comparison with an alternative regimen from the information in this record. The record’s termination status also does not itself establish why the study ended or what its outcomes were.
In general, a treatment result must be interpreted in light of its design, endpoint, analysis population, and uncertainty. Here, the registry does not report enough statistical detail to assess precision or reproduce the primary analysis. The adverse-event counts do not include a comparison group and do not show whether events were attributable to treatment. The appropriate reading is therefore narrow: the registry describes a dose-finding study and records adverse events, while leaving the primary dose-finding result and the preliminary efficacy question unanswered in its posted results.
13. Why This Trial Matters Statistically
This study illustrates a central statistical distinction in early clinical research: a dose-finding objective is not the same as a comparative efficacy objective. The primary question is the maximum tolerated dose of ridaforolimus with cetuximab. The study’s stated secondary purpose includes tolerability across dosing schedules, while the summary separately mentions preliminary information about whether the combination is helpful in advanced head and neck cancer. These questions require different endpoint definitions and interpretations.
The registry gives dose levels of 20 mg/day, 30 mg/day, and 40 mg/day, plus a brief account of toxicity review after the first 3 patients have received 1 cycle. Yet the toxicity criteria and full decision rules are not reported. This matters statistically because a dose-finding conclusion depends on how toxicity is defined, when it is assessed, and how observed toxicities guide subsequent dose decisions. Without those details or the resulting endpoint, readers cannot reconstruct the dose-selection process.
The study is single group, with allocation NA and no masking. Such a design can describe outcomes among enrolled participants, but it does not provide a concurrent control for interpreting changes in disease outcomes or adverse-event frequencies. The posted safety counts are useful as descriptive information, but they do not quantify a treatment effect relative to another option.
The record also shows why registry completeness is part of statistical interpretation. It identifies the planned enrollment and study status but does not post primary endpoint results, analyses, missing-data rules, or analysis populations. The combination is named, but the listed intervention and schedule details focus on ridaforolimus. These gaps constrain what readers can conclude and what other researchers can reproduce. The statistical lesson is not that the study had no meaningful findings, but that the registry record does not report enough to evaluate such findings.
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 principal limitation is that the registry record does not report the primary endpoint result. Although the endpoint is the maximum tolerated dose of ridaforolimus with cetuximab, no selected dose or dose-limiting toxicity results by level are posted. The brief escalation description is not a full protocol: exact toxicity criteria, the complete decision algorithm, and rules for participants with incomplete assessments are not reported.
The dosing information is not fully consistent in its wording. The arm description states 20mg daily, 5 days each week, on a 28 day cycle until progression, while the endpoint description labels dose levels “Weekly Ridaforolimus Dose Level” and lists 20 mg/day, 30 mg/day, and 40 mg/day. The record does not clarify the schedule for each dose level. It names cetuximab as part of the combination but does not report its dose or administration schedule. This restricts interpretation of the actual regimen.
The listed condition is non-small cell lung cancer, while the title and summary include head and neck, lung, and colon cancer. The record does not report the number enrolled by cancer type, baseline characteristics, or cancer-specific outcomes. It is therefore not possible to assess how the enrolled group relates to the broader population described in the summary. The planned enrollment was 12, but the record does not state whether that target was reached.
The study is single group and has no posted control comparison. The safety counts consequently cannot establish relative risk, and the preliminary efficacy question cannot be answered with a comparative estimate. The record is marked terminated, but the reason is not reported. Statistical analysis details—including the analysis population, missing-data approach, multiplicity handling, and inferential results—are also not reported in the registry record. These limitations leave the study’s central dose-finding outcome and its preliminary treatment question unresolved in the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ridaforolimus With Cetuximab: Adv Non-Small Cell Lung, Colorectal, Head & Neck Cancer — NCT01212627.
- Registry record last updated 2021-02-16; status last verified 2021-01.
- Results first posted 2015-06-25.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes NCT01212627 as a phase I, single-group study of ridaforolimus with cetuximab for advanced head and neck, non-small cell lung, and colon cancer. Planned enrollment was 12; the record is marked terminated. The primary objective was to determine the maximum tolerated dose of ridaforolimus with cetuximab. The summary also describes safety and side effects as aims and mentions preliminary information about the combination in advanced head and neck cancer.
The record lists dose levels of 20 mg/day, 30 mg/day, and 40 mg/day and describes toxicity review after the first 3 patients have received 1 cycle. It does not report a primary endpoint result, dose-limiting toxicity results, or inferential analyses. Serious adverse event figures are reported for the study group, but there is no comparator. The deaths value and the reason for termination are not reported in the registry record. Overall, the entry documents the study’s aims and some safety counts, but does not provide enough results or analysis detail to determine the maximum tolerated dose or assess the preliminary efficacy question.