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 A Study of LY2090314 in Patients With Advanced or Metastatic Cancer (NCT01287520), a na phase 1 study. The primary outcome is Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD]).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01287520 |
| Phase | Phase 1 |
| Condition | Advanced Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 41 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced or metastatic cancer. The registry lists the condition as Advanced Cancer and describes the primary endpoint population as participants who received at least one dose of study drug.
Intervention
LY2090314 in combination with pemetrexed and carboplatin. The study used dose escalation, and the registry also lists ranitidine as an intervention.
Comparator
There was no separate control group. This was a single-group study with no randomized comparison; its dose cohorts should not be read as like-for-like treatment arms.
Primary question
What dose and dosing regimen of LY2090314, when combined with pemetrexed and carboplatin, could be recommended for Phase 2 study? The primary endpoint was the recommended Phase 2 dose, defined through a maximum tolerated dose assessment based on dose-limiting toxicities during Cycle 1.
This is a dose-finding question rather than a test of whether the combination is better than another treatment. The registry summary describes Part A as dose escalation and Part B as an expanded cohort intended to confirm the dose selected from Part A. The endpoint description sets out rules for escalating, expanding, or stopping a dose cohort in response to observed toxicities. However, the registry record does not report the dose identified as the maximum tolerated dose or recommended for Phase 2.
The record also lists pharmacokinetic outcomes for LY2090314, pemetrexed, and free carboplatin, as well as best overall tumor response. These outcomes add descriptive information about drug exposure and tumor response, but the registry record does not report numerical results for them. With no control group and no reported primary endpoint result, the record cannot establish a comparative treatment effect.
3. Trial Design
This was a completed Phase 1, single-group study sponsored by Eli Lilly and Company. The registry reports an enrollment of 41 and identifies the condition as Advanced Cancer. The study began in 2007-11, had primary completion in 2011-04, and is listed as completed. Allocation is recorded as not applicable, and masking as none.
The official title describes a dose-escalation study of LY2090314 combined with pemetrexed and carboplatin in patients with advanced or metastatic cancer. The brief summary describes two parts: Part A was dose escalation, while Part B was an expanded cohort to confirm the dose selected from Part A. The registry's primary endpoint timeframe is baseline up to Day 28 of Cycle 1. The listed dose-limiting toxicity rules also focus on events during Cycle 1, which is described as 28 days.
The adverse-event record contains cohorts with different LY2090314 and carboplatin doses, alongside pemetrexed. Some cohort titles also include R50. These are dose cohorts within a dose-finding study, not randomized treatment groups. Cohort sizes are small and differ, so apparent differences in event counts across cohorts cannot be interpreted as controlled estimates of dose effects. The registry does not report the full dosing schedule for every cohort; the available arm description is incomplete.
The intervention list includes LY2090314, pemetrexed, carboplatin, and ranitidine. The record gives no separate comparator regimen. As a result, the design is suited to describing dose escalation and toxicity within the study regimen, not to estimating how the regimen compares with another treatment.
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: The reasons for discontinuation listed in the participant flow are the reasons the participant discontinued treatment and a participant was considered to have "completed" the trial if they discontinued treatment due to progressive disease or an adverse event.
Only the first 6 of 9 groups are shown.
Overall Study
| Stage | LY 10/Carb 5/Pem 500 (Cohort 1) | LY 10/Carb 6/Pem 500 (Cohort 2) | LY 20/Carb 6/Pem 500 (Cohort 3) | LY 40/Carb 6/Pem 500 (Cohort 4) | LY 80/Carb 6/Pem 500 (Cohort 5) | LY 120/Carb 6/Pem 500 -(Cohort 6) |
|---|---|---|---|---|---|---|
| STARTED | 3 | 7 | 5 | 7 | 3 | 4 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 7 | 5 | 7 | 3 | 4 |
Reasons for not completing this period:
| Reason | LY 10/Carb 5/Pem 500 (Cohort 1) | LY 10/Carb 6/Pem 500 (Cohort 2) | LY 20/Carb 6/Pem 500 (Cohort 3) | LY 40/Carb 6/Pem 500 (Cohort 4) | LY 80/Carb 6/Pem 500 (Cohort 5) | LY 120/Carb 6/Pem 500 -(Cohort 6) |
|---|---|---|---|---|---|---|
| Adverse Event | 2 | 2 | 2 | 1 | 1 | 2 |
| Physician Decision | 1 | 1 | 2 | 0 | 1 | 1 |
| Progressive disease | 0 | 4 | 1 | 6 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety population: all participants who have received at least 1 dose of the study drug.
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: All randomized participants who received at least 1 dose of study drug.
Only the first 6 of 10 groups are shown.
| Characteristic | Unit | LY 10/Carb 5/Pem 500 (Cohort 1) | LY 10/Carb 6/Pem 500 (Cohort 2) | LY 20/Carb 6/Pem 500 (Cohort 3) | LY 40/Carb 6/Pem 500 (Cohort 4) | LY 80/Carb 6/Pem 500 (Cohort 5) | LY 120/Carb 6/Pem 500 (Cohort 6) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 7 | 5 | 7 | 3 | 4 | |
| Age, Continuous | years | 55.81 (SD 11.88) | 55.27 (SD 9.19) | 59.31 (SD 5.62) | 58.32 (SD 8.95) | 57.35 (SD 7.59) | 56.73 (SD 7.52) |
| Sex: Female, Male: Female | Participants | 2 | 3 | 5 | 3 | 2 | 0 |
| Sex: Female, Male: Male | Participants | 1 | 4 | 0 | 4 | 1 | 4 |
| Race/Ethnicity, Customized: African | participants | 0 | 0 | 1 | 0 | 1 | 0 |
| Race/Ethnicity, Customized: Caucasian | participants | 3 | 6 | 4 | 7 | 2 | 4 |
| Race/Ethnicity, Customized: Hispanic | participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 3 | 7 | 5 | 7 | 3 | 4 |
| Body Surface Area | meters squared (m^2) | 1.76 (SD 0.11) | 2.10 (SD 0.13) | 1.66 (SD 0.14) | 1.94 (SD 0.29) | 1.77 (SD 0.46) | 2.11 (SD 0.33) |
| Eastern Cooperative Oncology Group (ECOG) performance: 0 | participants | 3 | 5 | 5 | 7 | 2 | 4 |
| Eastern Cooperative Oncology Group (ECOG) performance: 1 | participants | 0 | 2 | 0 | 0 | 1 | 0 |
| Basis of Diagnosis: Cytological | participants | 1 | 1 | 1 | 1 | 2 | 0 |
| Basis of Diagnosis: Histopathological | participants | 2 | 6 | 4 | 6 | 1 | 4 |
| Initial Pathological Tumor Diagnosis: Mesothelioma | participants | 2 | 3 | 1 | 0 | 0 | 1 |
| Initial Pathological Tumor Diagnosis: Non-small cell lung carcinoma (NSCLC) | participants | 0 | 0 | 3 | 1 | 1 | 0 |
| Initial Pathological Tumor Diagnosis: Leimyosarcoma | participants | 0 | 2 | 0 | 0 | 0 | 1 |
| Initial Pathological Tumor Diagnosis: Esophagus | participants | 0 | 0 | 0 | 1 | 1 | 0 |
| Initial Pathological Tumor Diagnosis: Lung adenocarcinoma | participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Pathological Tumor Diagnosis: Rectum | participants | 0 | 1 | 0 | 0 | 0 | 1 |
| Initial Pathological Tumor Diagnosis: Small cell lung carcinoma (SCLC) | participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Initial Pathological Tumor Diagnosis: Gastric | participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Initial Pathological Tumor Diagnosis: Head and neck | participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Initial Pathological Tumor Diagnosis: Adenocarcinoma not otherwise specified (NOS) | participants | 0 | 1 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD]), measured over Baseline up to Day 28 (Cycle 1).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | milligrams (mg) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the recommended LY2090314 dose for Phase 2 studies, expressed as a maximum tolerated dose. It is a dose-finding endpoint: rather than measuring a difference between treatments, it applies prespecified toxicity rules to decide whether a cohort can proceed, should be expanded, or should stop because the dose is considered to exceed the maximum tolerated dose.
The registry says that when a dose-limiting toxicity occurred in 1 of 3 participants, the cohort was to be expanded to 6 participants. If a dose-limiting toxicity occurred in 2 or more participants, accrual to that cohort was to stop. A dose-limiting toxicity was defined as a possibly related adverse event in Cycle 1 that met specified severity or duration criteria. Those criteria included certain severe nonhematologic toxicities, prolonged severe hematologic toxicity, febrile neutropenia, specified thrombocytopenia events, and a prolonged QTc interval.
Using a defined early-cycle toxicity window gives the dose-escalation process a consistent basis for judging tolerability. It is a measure of toxicity under the study's rules, not a direct measure of tumor control or comparative benefit. The registry record does not report the resulting maximum tolerated dose or recommended Phase 2 dose, so the primary endpoint outcome is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes the study's dose-finding framework but does not report the primary endpoint result. In particular, it does not state the maximum tolerated dose or the LY2090314 dose recommended for Phase 2 studies. It therefore is not possible to identify a selected dose from the registry record or to judge how the stated decision rules were applied to the observed dose-limiting toxicities.
The adverse-event entries provide counts by cohort. They show that serious adverse events were reported in several cohorts, with counts ranging from 0 of 5 in the LY 60/Carb 6/Pem 500 + R50 cohort to 3 of 7 in the LY 10/Carb 6/Pem 500 cohort. Other adverse events were reported in most or all participants in each listed cohort. These are descriptive counts in small, differently dosed cohorts. They do not establish a dose-related pattern or support a comparison of regimens, particularly because there was no randomized control group.
The registry lists pharmacokinetic outcomes for LY2090314 alone and in combination, pemetrexed, and free carboplatin, and lists best overall tumor response. It does not report numerical results for these outcomes. Thus, the posted record cannot show the distribution of drug exposure, the observed tumor-response categories, or how those outcomes relate to dose or toxicity.
The statistical interpretation is consequently limited to the recorded design, endpoint definition, and adverse-event counts. No inferential analysis is reported in the registry record. There are no reported confidence intervals or comparative estimates to quantify uncertainty around a treatment contrast. In general, small cohort counts are imprecise: a difference of a few events can materially change the apparent pattern, and the counts alone do not distinguish a real dose effect from chance variation.
The result should not be read as evidence for or against the clinical effectiveness of the combination. This was a Phase 1 dose-escalation study, and its primary question concerned dose selection based on early toxicity. Even if tumor responses were reported, a single-group design would not by itself establish what would have happened under a different treatment. The registry record does not report enough outcome detail to assess response, pharmacokinetics, or the selected dose.
9. Statistical Methods Explained
What does dose escalation mean in this study?
In general, dose escalation is a staged approach: participants receive regimens at different dose levels, and the next dosing decision depends on observed toxicity under defined rules. It differs from a randomized comparison, where treatment assignment is used to create groups intended for a direct contrast. Here, allocation is listed as not applicable, masking as none, and the model as single group. The dose cohorts therefore describe stages of the study rather than interchangeable treatment arms.
The registry says a cohort was to expand when a dose-limiting toxicity occurred in 1 of 3 participants, and that accrual to a cohort was to stop if such toxicity occurred in 2 or more participants. These rules describe the planned decision process. They do not, by themselves, reveal which dose was selected or whether any cohort was expanded or stopped. The outcome of that process is not reported in the registry record.
How should the toxicity endpoint be understood?
The primary endpoint uses dose-limiting toxicity in Cycle 1, described as 28 days, to support dose selection. The event definition combines timing, possible relation to study drug, and clinical severity or duration criteria. In general, a rule-based toxicity endpoint makes the decision criteria more explicit, but it remains dependent on the recorded events, their attribution, and the population assessed. The registry defines the safety population as all participants who received at least one dose of study drug.
The endpoint is not a statistical comparison of the combination against a control treatment. It is also distinct from the listed pharmacokinetic endpoints and best overall tumor response. Those outcomes address drug exposure and tumor response, respectively, while the primary endpoint concerns a tolerability-based dose recommendation. The registry does not report numerical outcomes for these endpoints.
Why are cohort counts not a controlled comparison?
The adverse-event record lists cohorts at different doses, with differing numbers of participants and some cohort titles including R50. Because the study was not randomized and has no separate control arm, direct contrasts between cohorts can be confounded by the dose-escalation sequence and other differences in how the cohorts were formed. General statistical reasoning cautions against treating variation in observed counts as proof of a dose effect. The record does not provide an adjusted analysis to address such differences.
Small counts also make percentages unstable: a single participant's event can change the proportion noticeably. A percentage or count in one cohort should therefore be read as a description of that cohort, not as a precise estimate of risk in a broader population. No confidence intervals or other uncertainty estimates for these cohort counts are reported in the registry record.
What can pharmacokinetic outcomes add?
Pharmacokinetic measures describe drug concentration over time. The listed outcomes include area under the concentration-time curve and maximum plasma concentration for LY2090314, including when coadministered with pemetrexed and carboplatin; area under the curve and maximum concentration for pemetrexed; and area under the curve for free carboplatin. In general, these measures help characterize exposure, but the record's endpoint list is not itself a result. Numerical pharmacokinetic estimates are not reported in the registry record.
What analyses and precision estimates are available?
The registry lists no analyses. It does not report p-values, confidence intervals, adjusted estimates, or a statistical model for the outcomes. A confidence interval, in general, expresses the range of values compatible with an estimate under a specified method; without an estimate and interval, the precision of a result cannot be assessed. No sample-size justification or interim-analysis plan is reported in the registry record.
The study is identified as Phase 1 and its primary question is dose finding, not a two-arm efficacy contrast. The registry's design and outcome details do not support an inferential comparison of treatment effects. Any planning illustration based on an observed effect would also require a defined comparison and effect estimate, neither of which is reported for the primary endpoint. Such an illustration would be a planning exercise, not observed power or evidence about the study's result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures, including the primary dose-finding endpoint, pharmacokinetic measures, and best overall tumor response. When a study assesses multiple outcomes, general statistical practice considers multiplicity: the more hypotheses tested, the greater the chance of at least one apparently notable result arising by chance. That concern is most relevant when multiple inferential tests are conducted. The registry record reports no analyses, and it does not report a multiplicity adjustment or a strategy for prioritizing secondary results.
Missing-data methods and the amount of missing outcome data are not reported in the registry record. It is therefore not possible to determine whether all enrolled participants contributed to each endpoint, how incomplete pharmacokinetic measurements were handled, or how missing tumor-response assessments were treated. The primary endpoint identifies a safety population of participants who received at least one dose, but further analysis-population details are not reported in the registry record.
The record does not describe an interim-analysis plan, nor does it report a sample-size justification. These omissions limit assessment of how the study was planned and how missingness or multiple outcomes might affect interpretation. They do not establish that such procedures were absent; their details are simply not reported in 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 |
|---|---|---|---|
| LY 10/Carb 5/Pem 500 (Cohort 1) | 1 | 3 | 33.3% |
| LY 10/Carb 6/Pem 500 (Cohort 2) | 3 | 7 | 42.9% |
| LY 20/Carb 6/Pem 500 (Cohort 3) | 3 | 5 | 60.0% |
| LY 40/Carb 6/Pem 500 (Cohort 4) | 2 | 7 | 28.6% |
| LY 80/Carb 6/Pem 500 (Cohort 5) | 1 | 3 | 33.3% |
| LY 120/Carb 6/Pem 500 (Cohort 6) | 1 | 4 | 25.0% |
| LY 80/Carb 6/Pem 500 + R50 (Cohort 7) | 1 | 2 | 50.0% |
| LY 60/Carb 6/Pem 500 + R50 (Cohort 8) | 0 | 5 | 0.0% |
| LY 40/Carb 6/Pem 500 + R50 (Cohort 9) | 1 | 5 | 20.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| LY 10/Carb 5/Pem 500 (Cohort 1) | 3 of 3 |
| LY 10/Carb 6/Pem 500 (Cohort 2) | 7 of 7 |
| LY 20/Carb 6/Pem 500 (Cohort 3) | 5 of 5 |
| LY 40/Carb 6/Pem 500 (Cohort 4) | 7 of 7 |
| LY 80/Carb 6/Pem 500 (Cohort 5) | 3 of 3 |
| LY 120/Carb 6/Pem 500 (Cohort 6) | 3 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | LY 10/Carb 5/Pem 500 (Cohort 1) | LY 10/Carb 6/Pem 500 (Cohort 2) | LY 20/Carb 6/Pem 500 (Cohort 3) | LY 40/Carb 6/Pem 500 (Cohort 4) | LY 80/Carb 6/Pem 500 (Cohort 5) | LY 120/Carb 6/Pem 500 (Cohort 6) |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 3 | 1 of 7 | 0 of 5 | 1 of 7 | 0 of 3 | 0 of 4 |
| Dehydration | Metabolism and nutrition disorders | 0 of 3 | 0 of 7 | 0 of 5 | 1 of 7 | 1 of 3 | 0 of 4 |
| Angina pectoris | Cardiac disorders | 0 of 3 | 0 of 7 | 0 of 5 | 0 of 7 | 0 of 3 | 1 of 4 |
| Nausea | Gastrointestinal disorders | 0 of 3 | 0 of 7 | 0 of 5 | 0 of 7 | 1 of 3 | 0 of 4 |
| Rectal haemorrhage | Gastrointestinal disorders | 0 of 3 | 0 of 7 | 1 of 5 | 0 of 7 | 0 of 3 | 0 of 4 |
| Vomiting | Gastrointestinal disorders | 0 of 3 | 0 of 7 | 0 of 5 | 0 of 7 | 1 of 3 | 0 of 4 |
| Pneumonia | Infections and infestations | 1 of 3 | 0 of 7 | 0 of 5 | 0 of 7 | 0 of 3 | 0 of 4 |
| Pseudomembranous colitis | Infections and infestations | 0 of 3 | 0 of 7 | 1 of 5 | 0 of 7 | 0 of 3 | 0 of 4 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 3 | 0 of 7 | 0 of 5 | 1 of 7 | 0 of 3 | 0 of 4 |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | 0 of 3 | 1 of 7 | 0 of 5 | 0 of 7 | 0 of 3 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | LY 10/Carb 5/Pem 500 (Cohort 1) | LY 10/Carb 6/Pem 500 (Cohort 2) | LY 20/Carb 6/Pem 500 (Cohort 3) | LY 40/Carb 6/Pem 500 (Cohort 4) | LY 80/Carb 6/Pem 500 (Cohort 5) | LY 120/Carb 6/Pem 500 (Cohort 6) |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 3 of 3 | 6 of 7 | 5 of 5 | 5 of 7 | 2 of 3 | 0 of 4 |
| Anaemia | Blood and lymphatic system disorders | 2 of 3 | 6 of 7 | 5 of 5 | 5 of 7 | 2 of 3 | 0 of 4 |
| Nausea | Gastrointestinal disorders | 1 of 3 | 6 of 7 | 3 of 5 | 4 of 7 | 1 of 3 | 1 of 4 |
| Thrombocytopenia | Blood and lymphatic system disorders | 2 of 3 | 3 of 7 | 2 of 5 | 6 of 7 | 2 of 3 | 0 of 4 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 3 | 4 of 7 | 2 of 5 | 5 of 7 | 3 of 3 | 0 of 4 |
| Vomiting | Gastrointestinal disorders | 1 of 3 | 2 of 7 | 2 of 5 | 3 of 7 | 3 of 3 | 1 of 4 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 3 | 3 of 7 | 2 of 5 | 4 of 7 | 2 of 3 | 1 of 4 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 3 of 7 | 2 of 5 | 4 of 7 | 1 of 3 | 1 of 4 |
| Leukopenia | Blood and lymphatic system disorders | 0 of 3 | 4 of 7 | 1 of 5 | 3 of 7 | 2 of 3 | 0 of 4 |
| Lymphopenia | Blood and lymphatic system disorders | 0 of 3 | 4 of 7 | 1 of 5 | 3 of 7 | 0 of 3 | 1 of 4 |
Serious events with the highest arm-level rate: chest pain (50.0%), nausea (33.3%), vomiting (33.3%), pneumonia (33.3%), dehydration (33.3%).
The serious adverse-event entries are counts of participants affected within each cohort, alongside the number at risk. For example, the LY 10/Carb 5/Pem 500 cohort reports serious adverse events in 1 of 3 participants, while the LY 60/Carb 6/Pem 500 + R50 cohort reports 0 of 5. The other-adverse-event counts are reported separately; in the first of those cohorts, 3 of 3 participants were affected. These categories should not be combined or treated as interchangeable.
The registry also lists serious-event terms and percentages: Chest pain, 50.0%; Nausea, 33.3%; Vomiting, 33.3%; Pneumonia, 33.3%; Dehydration, 33.3%; and Angina pectoris, 25.0%. The record does not give the denominator or further context for these term percentages, so they should be read as listed rather than interpreted as a risk estimate for all participants.
Cohorts had different doses and sizes and were not randomized comparison groups. Their counts are descriptive and do not establish that a regimen caused more or fewer events than another. Death counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase 1, single-group dose-escalation study was conducted to identify a recommended Phase 2 dose of LY2090314 with pemetrexed and carboplatin. It provides the primary endpoint's toxicity-based decision rules and reports adverse-event counts across dose cohorts. Those details describe how the study was organized and some of the safety events recorded.
The main result needed to answer the study's primary question is missing: the registry record does not report the maximum tolerated dose or recommended Phase 2 dose. It also does not report numerical results for the listed pharmacokinetic outcomes or best overall tumor response. The design and posted results therefore do not establish what dose was selected, what drug exposures were observed, or what tumor responses occurred.
Even a complete dose-finding result would answer a narrower question than whether a treatment is effective relative to another option. In general, a single-group study cannot provide the same controlled treatment contrast as a randomized comparison. The cohorts also differed in dose and size, so their event counts should not be treated as direct estimates of comparative safety.
The reported safety counts can be used to describe the cohorts in this record, but they do not establish the frequency of events in a broader patient population. The small cohort counts and absence of reported uncertainty estimates limit precision. No medical conclusion about treatment benefit or lack of benefit follows from the information reported in the registry.
13. Why This Trial Matters Statistically
This study illustrates a different statistical aim from a conventional treatment-comparison trial. In dose escalation, the central task is to use observed toxicity under defined rules to guide selection of a dose for later study. The endpoint is a dose recommendation based on safety observations, not an estimate of the difference in outcome between treatment arms.
That distinction matters when reading cohort-level results. Different dose cohorts may appear to have different adverse-event counts, but the cohorts are not randomized controls and differ in size. A numerical contrast between them would not automatically isolate the effect of dose. Interpreting the figures descriptively, rather than as a comparative estimate, respects what this design can show.
The record also demonstrates why a clearly defined endpoint is not enough to assess a study's finding: the endpoint rules are described, but the result of applying them is not reported. Without the selected dose, dose-limiting toxicity results, or numerical pharmacokinetic and tumor-response outcomes, the statistical question cannot be answered from this record. Clear separation of endpoint definition from outcome reporting is essential to avoid mistaking a protocol rule for a result.
Finally, the listed secondary outcomes span drug exposure and tumor response, but no analyses or numerical results are reported. A careful reading distinguishes the range of outcomes the study intended to assess from the evidence actually available in the registry record. That distinction is important for dose-finding studies, where descriptive safety data, pharmacokinetic characterization, and later comparative efficacy testing serve different purposes.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most important limitation for interpretation is that the registry record does not report the primary endpoint outcome: the maximum tolerated dose or the recommended Phase 2 dose. It also does not report numerical results for the listed secondary outcomes, including pharmacokinetic measures and best overall tumor response. Consequently, the planned dose-finding question cannot be resolved from the posted results.
The study was single group, with no randomized control. Its cohorts had different dose regimens and sizes, so the adverse-event counts do not constitute a like-for-like comparison. The record reports small cohort counts, and no confidence intervals or other precision estimates are given. The listed serious-event term percentages also lack a reported denominator and context in the record.
The registry's available arm description is incomplete, and the record does not report full dosing details for every cohort. It does not report missing-data handling, analysis populations beyond the safety-population definition for the primary endpoint, a multiplicity strategy, or a sample-size justification. No interim-analysis details are reported. These items are not reported in the registry record, which limits assessment of how outcomes were analyzed and how robust the results would be.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of LY2090314 in Patients With Advanced or Metastatic Cancer — NCT01287520.
- Registry record last updated 2019-02-25; status last verified 2018-10.
- Results first posted 2019-02-25.
- 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.
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18. Record Summary
NCT01287520 is a completed Phase 1, single-group dose-escalation study of LY2090314 with pemetrexed and carboplatin in patients with advanced or metastatic cancer. The registry reports enrollment of 41, a study start in 2007-11, and primary completion in 2011-04. Part A involved dose escalation; Part B was described as an expanded cohort to confirm the dose selected from Part A.
The primary endpoint was the recommended Phase 2 dose, defined through a maximum tolerated dose assessment using dose-limiting toxicities during Cycle 1. The registry describes the decision rules but does not report the selected dose. It reports adverse-event counts across cohorts but no randomized comparator or inferential analyses. Numerical results for the listed pharmacokinetic and tumor-response outcomes are not reported in the registry record.