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 Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer (NCT03263429), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (Phase I) of CB-839 in Combination With Panitumumab and Irinotecan Hydrochloride.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03263429 |
| Phase | Phase 1, Phase 2 |
| Condition | Colorectal Cancer, Metastatic Colorectal Cancer, RAS Wild Type Colorectal Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanderbilt-Ingram Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with metastatic and refractory RAS wildtype colorectal cancer. The registry record lists colorectal cancer, metastatic colorectal cancer, RAS wild type colorectal cancer, and refractory colorectal cancer as conditions. It records enrollment of 29. Further eligibility criteria and characteristics of the enrolled participants are not reported in the registry record.
Intervention
The regimen combined oral glutaminase inhibitor CB-839 with intravenous panitumumab. Irinotecan hydrochloride was included in Phase I only. The described schedule gives CB-839 twice daily on days 1-28, panitumumab on days 1 and 15, and irinotecan on days 1 and 15; courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. The record also lists laboratory biomarker analysis, pharmacological study, and imaging with 11C-glutamine and 18F-FSPG PET/CT scans.
Comparator
There was no randomized comparator: allocation is recorded as not applicable, masking as none, and the model as single group. The described treatment groups are dose-escalation and dose-expansion groups, not like-for-like control groups. Consequently, differences between their safety counts cannot be interpreted as treatment effects relative to a control.
Primary question
The primary Phase I question was the maximum tolerated dose of CB-839 when combined with panitumumab and irinotecan hydrochloride. The listed primary measure is a number in mg, with a timeframe of up to 12 months. The record describes dose escalation using a Bayesian continual reassessment method and cohorts of 3. It does not report the determined maximum tolerated dose, the observed primary endpoint value, or the detailed toxicity criteria used to define that dose. The study also listed efficacy, survival, and imaging or biomarker outcomes, but their results are not reported in the registry record.
3. Trial Design
This was a completed Phase I/II study sponsored by Vanderbilt-Ingram Cancer Center. The registry record gives a start date of 2017-08-23 and a primary completion date of 2023-08-15, and records enrollment of 29. It describes a single-group model, no masking, and allocation as not applicable. These features mean the design was not a randomized comparison with a separate control group.
The Phase I component aimed to determine the maximum tolerated dose of CB-839 in combination with panitumumab and irinotecan hydrochloride. The record describes Bayesian continual reassessment for dose escalation and cohorts of 3. Dose levels listed in the primary endpoint description are 400, 600 and 800mg. The adverse-event groups identify a Phase I dose-escalation group at 600mg and one at 800mg. The registry also lists a Phase II dose-expansion group at 800mg. Detailed rules for moving between doses, stopping escalation, or selecting a dose are not reported in the registry record.
The described regimen used CB-839 by mouth twice daily on days 1-28, panitumumab intravenously on days 1 and 15, and, in Phase I only, irinotecan intravenously on days 1 and 15. Courses were described as repeating every 28 days if disease progression or unacceptable toxicity did not occur. The record lists imaging with 11C-glutamine PET/CT and 18F-FSPG PET/CT scans, along with laboratory biomarker and pharmacological studies. Details of scan timing and the complete assessment schedule are not reported in the registry record.
The single-group design can describe outcomes observed among treated participants, but it does not establish what would have happened under a different regimen or no study treatment. The dose groups also arose within the study’s dose-finding and expansion structure, so they are not like-for-like comparative arms.
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 | CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) |
|---|---|---|---|
| STARTED | 3 | 8 | 18 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 8 | 18 |
Reasons for not completing this period:
| Reason | CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) |
|---|---|---|---|
| Withdrawal by Subject | 0 | 1 | 0 |
| Follow-Up Period Completed | 0 | 2 | 0 |
| Death | 3 | 5 | 16 |
| Participant unable to return | 0 | 0 | 1 |
| Study Closed | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Patients got CB-839 combined with 6 mg/kg panitumumab, and 180 mg/m2 irinotecan.
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 | CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 8 | 18 | 29 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 1 | 16 | 19 |
| Age, Categorical: >=65 years | Participants | 1 | 7 | 2 | 10 |
| Sex: Female, Male: Female | Participants | 1 | 4 | 5 | 10 |
| Sex: Female, Male: Male | Participants | 2 | 4 | 13 | 19 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 2 | 1 | 4 |
| Race (NIH/OMB): White | Participants | 2 | 5 | 13 | 20 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 4 | 4 |
| Region of Enrollment: United States | participants | 3 | 8 | 18 | 29 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (Phase I) of CB-839 in Combination With Panitumumab and Irinotecan Hydrochloride, measured over Up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of CB-839, measured in mg, when combined with panitumumab and irinotecan hydrochloride during Phase I. In a dose-finding study, this endpoint is intended to identify a dose judged tolerable under the study’s specified toxicity rules. It is not itself a measure of tumor response or survival. The registry record says the dose was to be determined using Bayesian continual reassessment and that patients were treated in cohorts of 3.
The endpoint is useful for dose selection because early-phase research must characterize tolerability before a regimen is taken forward for further evaluation. A maximum tolerated dose is meaningful only in relation to the toxicity definition, observation period, and decision rules used. The primary endpoint description does not state the dose-limiting toxicity definition or the precise algorithmic rules; those details are not reported in the registry record. The listed timeframe is up to 12 months, but the exact timing of the dose determination is not specified.
No numerical maximum tolerated dose or associated uncertainty is reported in the registry record. The listed dose levels—400, 600 and 800mg—are dose levels, not a reported endpoint result. Therefore, the endpoint’s purpose can be described, but the registry record does not establish which dose was selected or how precise that selection was.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the study’s design and primary objective, but it does not report the numerical result for the primary endpoint. In particular, it does not state the maximum tolerated dose determined in Phase I or provide an uncertainty interval for that estimate. The dose levels listed in the record should not be mistaken for the selected maximum tolerated dose. Without the endpoint result and its supporting details, the primary dose-finding conclusion cannot be evaluated from the registry record.
The study is recorded as a single-group Phase I/II trial with no masking and no randomized allocation. Its safety counts describe participants in treatment groups with different dose and study-phase labels. These counts can be read as descriptive observations within those groups. They do not provide a controlled estimate of what the regimen caused, and differences between groups are not interpretable as causal dose effects: dose assignment and phase are not a like-for-like randomized comparison.
The registry lists Disease Control Rate, progression-free survival, overall survival, plasma exosomal content, and an imaging uptake-change relationship among secondary outcomes. It also lists a coefficient of determination for the relationship between change in 18F-FSPG uptake and tumor size change in Phase II. Outcome values, definitions for most measures, analysis details, and uncertainty estimates are not reported in the registry record. The study’s efficacy and biomarker findings therefore cannot be characterized from the listed outcome names alone.
The enrollment figure of 29 is a record-level study figure, not evidence that each outcome was evaluable for every enrolled participant. The analysis populations, participant flow, withdrawals, and amounts of missing outcome data are not reported in the registry record. Those omissions matter because an outcome estimate depends on who was assessed, when assessments occurred, and how unavailable measurements were handled.
General statistical interpretation: confidence intervals, when reported, describe the range of values compatible with the data and the analysis assumptions; they convey precision rather than certainty that a value is correct. No confidence interval for the primary endpoint or secondary outcomes is reported in the registry record. Accordingly, neither the size nor the precision of an efficacy, survival, imaging, or dose-finding effect can be judged from this record alone.
9. Statistical Methods Explained
The main stated statistical method is the Bayesian continual reassessment method for Phase I dose escalation. General explanation: a continual reassessment approach uses accumulating information about toxicity to guide which dose is considered for later participants. A Bayesian method represents uncertainty about the dose-toxicity relationship with a probability model and updates that uncertainty as observations accrue. The method’s decisions depend on the model, toxicity definition, target toxicity level, and escalation rules. The registry record does not report those details, so the actual operating rules or their appropriateness cannot be assessed from the record.
The record says patients were treated in cohorts of 3 and lists CB-839 dose levels of 400, 600 and 800mg. Cohort-based escalation is a feature of the described Phase I process, but the registry entry does not specify how many participants were treated at each dose for the primary analysis, how toxicity observations were attributed, or whether the listed levels were the full set considered. The group-specific safety counts provide some dose and phase labels, but they do not replace a full account of the escalation data or the dose-selection analysis.
The primary endpoint is a dose, expressed in mg, rather than a between-group mean or a time-to-event estimate. General explanation: a dose-finding estimate is interpreted through the model and the toxicity outcome that drives the dose decision. Reporting only a candidate dose without the underlying toxicity definition, data, and uncertainty would leave readers unable to judge how strongly the evidence supports the choice. Here, the determined dose and its uncertainty are not reported in the registry record.
The posted planning assumptions describe an illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the illustration refers to total events using the Schoenfeld approach; other calculations are described as participants per arm. These are planning assumptions, not the study’s documented design. In particular, the trial is recorded as single group, not as an equal-allocation, two-arm randomized trial. Such planning illustrations are not observed power and do not constitute evidence about the study’s outcomes. Numerical planning results and the observed effect used for the illustration are not reported in the registry record.
General explanation: sample-size planning asks how much information a future study might need under chosen assumptions. Its answer depends on the target effect, variability or event rate, significance level, desired power, allocation, and analysis method. A calculation based on a previously observed effect can be optimistic if that effect is imprecise or unusually large. It should not be treated as a prediction of what a new study will observe. Nor can an illustrative two-arm calculation be read as a retrospective assessment of a single-group dose-finding study.
The registry records eight outcome measures, including safety, disease control, survival, imaging, and biomarker outcomes. It records no analysis entries. General explanation: analysis methods should match the outcome type and the study question. Counts and proportions describe categorical outcomes; survival methods account for time to an event and censoring; and correlation or regression methods can examine relationships between continuous measurements. The registry outcome names do not specify which methods were used for each outcome, the analysis populations, adjustment variables, or uncertainty estimates. These details are not reported in the registry record.
For the Phase II imaging measure, the registry names a coefficient of determination, R2, relating change in 18F-FSPG uptake to change in tumor size. General explanation: R2 describes how much of the variation in one measure is accounted for by a fitted relationship with another, under the particular model used. It does not by itself establish causation, and its interpretation depends on the data and model. The actual R2, its uncertainty, and the analysis details are not reported in the registry record.
For survival outcomes, the registry lists progression-free survival and overall survival. General explanation: time-to-event estimates depend on event definitions, follow-up, censoring, and the analysis method. A survival outcome cannot be fully interpreted from its name alone. The event definitions, follow-up summaries, estimates, and uncertainty are not reported in the registry record. The same caution applies to the listed disease control and plasma exosomal outcomes: names alone do not establish how they were defined or analyzed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures, spanning safety, disease control, survival, imaging, and biomarker questions. It records no analysis entries. The record does not describe a hierarchy among the outcomes, identify a single confirmatory secondary endpoint, or state how the risk of false-positive findings across multiple analyses was addressed. A multiplicity plan is not reported in the registry record.
General explanation: when many outcomes or analyses are examined, the chance of obtaining an apparently notable result by chance can increase. Prespecifying a primary outcome and controlling or otherwise addressing multiplicity can help readers distinguish confirmatory analyses from exploratory ones. The primary endpoint is identified as the Phase I maximum tolerated dose, but the registry record does not provide a complete statistical analysis plan for the other outcomes.
Missing-data methods and analysis populations are not reported in the registry record. The entry does not state how many participants contributed to each endpoint, whether participants who discontinued treatment were followed for outcomes, or how missing measurements were handled. Enrollment is recorded as 29, but that figure alone does not show the number assessed for any particular outcome.
General explanation: missing measurements can affect an estimate when the likelihood of missingness is related to participants’ health, treatment experience, or outcome values. Complete-case analyses, imputation, and sensitivity analyses make different assumptions; readers need the analysis description to understand those assumptions. The registry record does not indicate which, if any, such methods were used.
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 |
|---|---|---|---|
| CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | 1 | 3 | 33.3% |
| CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | 3 | 8 | 37.5% |
| CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) | 4 | 18 | 22.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | 3 of 3 |
| CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | 8 of 8 |
| CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) | 17 of 18 |
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 |
|---|---|
| CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | 3 of 3 |
| CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | 8 of 8 |
| CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) | 18 of 18 |
Most frequent serious adverse event terms
| Event term | Organ system | CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) |
|---|---|---|---|---|
| Kidney Injury | Renal and urinary disorders | 0 of 3 | 2 of 8 | 0 of 18 |
| Bowel obstruction | Gastrointestinal disorders | 1 of 3 | 0 of 8 | 0 of 18 |
| Neutrophil Count Decrease | Investigations | 0 of 3 | 1 of 8 | 0 of 18 |
| Ileus | Gastrointestinal disorders | 0 of 3 | 1 of 8 | 0 of 18 |
| Difficile: related to antibiotic use | Infections and infestations | 0 of 3 | 1 of 8 | 0 of 18 |
| Dehydration | Gastrointestinal disorders | 0 of 3 | 1 of 8 | 0 of 18 |
| Biliary Obstruction | Hepatobiliary disorders | 0 of 3 | 0 of 8 | 1 of 18 |
| Confusion | Psychiatric disorders | 0 of 3 | 0 of 8 | 1 of 18 |
| Brain Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 3 | 0 of 8 | 1 of 18 |
| Nausea | Gastrointestinal disorders | 0 of 3 | 0 of 8 | 1 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | CB-839 600mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan 180mg/m2 (Phase I Dose Escalation) | CB-839 800mg +Panitumumab 6mg/kg +Irinotecan180mg/m2 (Phase II Dose Expansion) |
|---|---|---|---|---|
| Rash acneiform | Skin and subcutaneous tissue disorders | 3 of 3 | 7 of 8 | 11 of 18 |
| Fatigue | General disorders | 3 of 3 | 7 of 8 | 9 of 18 |
| Anemia | Blood and lymphatic system disorders | 3 of 3 | 7 of 8 | 8 of 18 |
| Hypomagnesemia | Metabolism and nutrition disorders | 3 of 3 | 5 of 8 | 7 of 18 |
| Alkaline phosphtase increased | Investigations | 2 of 3 | 5 of 8 | 7 of 18 |
| Hyperglycemia | Metabolism and nutrition disorders | 0 of 3 | 1 of 8 | 13 of 18 |
| Nausea | Gastrointestinal disorders | 0 of 3 | 5 of 8 | 9 of 18 |
| Lymphocyte count decreased | Investigations | 1 of 3 | 5 of 8 | 7 of 18 |
| Alanine aminotransferase increased | Investigations | 2 of 3 | 3 of 8 | 7 of 18 |
| Aspartate aminotransferase increased | Investigations | 2 of 3 | 3 of 8 | 7 of 18 |
Serious events with the highest arm-level rate: bowel obstruction (33.3%), kidney injury (25.0%), neutrophil count decrease (12.5%), ileus (12.5%), difficile: related to antibiotic use (12.5%).
The adverse-event record separates three groups: CB-839 600mg in Phase I dose escalation, CB-839 800mg in Phase I dose escalation, and CB-839 800mg in Phase II dose expansion, each with panitumumab 6mg/kg and irinotecan 180mg/m2. The recorded numbers at risk are 3, 8, and 18, respectively. Serious adverse events affected 1, 3, and 4 participants in those groups; other adverse events affected 3, 8, and 18. The recorded death counts are 3, 8, and 17, respectively.
These are descriptive counts within the registry’s group labels. The record does not establish that an adverse event or death was caused by study treatment. It also does not report the timing, duration, severity grading system, participant-level overlap among event categories, or complete event narratives. Group counts should not be treated as directly comparable treatment effects because the groups differ by dose and study phase and there is no randomized control group.
The listed serious-event terms include bowel obstruction at 33.3%, kidney injury at 25.0%, neutrophil count decrease at 12.5%, ileus at 12.5%, difficile: related to antibiotic use at 12.5%, and dehydration at 12.5%. These percentages describe the registry’s serious-event listing; the record does not give the detailed event-level denominator or clarify whether individuals could contribute more than one event. The figures therefore describe reported safety experience, not a causal risk estimate for the regimen.
12. What the Result Does, and Does Not, Mean
This study’s primary question was a Phase I dose-finding question: what maximum tolerated dose of CB-839 should be identified when used with panitumumab and irinotecan hydrochloride? The registry record describes the Bayesian continual reassessment method, cohorts of 3, and dose levels of 400, 600 and 800mg. It does not report the selected maximum tolerated dose or the information needed to judge the precision of that selection. The primary result therefore cannot be stated from the registry record.
The record also documents a Phase II dose-expansion group and lists additional outcomes in disease control, survival, imaging, and plasma exosomal content. Their inclusion indicates that the study addressed questions beyond dose finding, but outcome names are not findings. Numerical results and analysis details for these outcomes are not reported in the registry record. No conclusion about the magnitude or precision of efficacy, survival, or biomarker associations can be drawn from the outcome list alone.
The safety counts show that adverse events and deaths were recorded in each listed group. They do not show whether events were treatment-related, and group differences cannot be attributed to dose because there was no randomized comparison and the groups represent different study phases. A descriptive count is not a causal estimate.
General explanation: a single-group study can characterize outcomes observed among participants who received a regimen, subject to the completeness and quality of assessment. Without a concurrent comparator, it cannot separate the regimen’s contribution from other influences on outcomes. That limitation is especially important when interpreting disease outcomes, survival, and changes in imaging biomarkers.
The registry status is completed, but completion status does not supply missing results. The record supports a description of the study question, treatment schedule, selected outcome categories, and posted safety counts. It does not, by itself, support a treatment-effect conclusion or a precise account of the primary dose-finding result.
13. Why This Trial Matters Statistically
This trial is statistically notable for combining a Phase I dose-finding question with a Phase II expansion in a single-group study. Phase I used a Bayesian continual reassessment method, according to the registry record, while the listed Phase II group was an expansion at CB-839 800mg with panitumumab and irinotecan. The design aims described in the record therefore include dose selection and later observation of outcomes, but these are distinct inferential tasks.
General explanation: dose-finding methods use accumulating safety information to guide dose selection, while later-phase outcome analyses ask how participants fare on a regimen. A selected dose is not itself evidence of comparative efficacy. Similarly, outcomes observed in a dose-expansion group can be informative descriptively, but a single-group design cannot provide the same causal comparison as a randomized control group.
The record also lists imaging and biomarker measures, including PET/CT imaging with 11C-glutamine and 18F-FSPG and a Phase II relationship between 18F-FSPG uptake change and tumor size change. Such measures raise statistical questions about measurement timing, repeatability, associations, and how many analyses are interpreted together. The detailed methods and numerical findings for these measures are not reported in the registry record.
The study record illustrates why interpretability depends not only on design labels and outcome names, but also on complete reporting of estimates, uncertainty, analysis populations, and analysis choices. Without those details, readers can identify the statistical questions the trial was designed to address but cannot evaluate the strength or precision of the answers.
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 registry record does not report the primary endpoint result, including the maximum tolerated dose determined in Phase I. It also does not provide an uncertainty estimate or the detailed toxicity criteria and decision rules used in the Bayesian continual reassessment method. These omissions prevent an assessment of the basis and precision of the dose-selection conclusion.
The study is recorded as single group, with allocation not applicable and masking none. There is no randomized control group described. The Phase I dose-escalation and Phase II dose-expansion groups differ in dose and phase, so their counts should not be treated as a controlled dose comparison. The record does not give sufficient participant-level or analysis information to account for such differences.
Although enrollment is recorded as 29, participant flow and endpoint-specific analysis populations are not reported in the registry record. The entry does not state how many participants were evaluated for each outcome, how missing observations were handled, or the extent and timing of follow-up. This is particularly relevant to progression-free and overall survival, which require clear event definitions and follow-up information.
The record lists eight outcome measures but no analysis entries. It does not provide a statistical analysis plan, multiplicity strategy, definitions for most secondary outcomes, or numerical results and uncertainty for the listed efficacy, imaging, and biomarker measures. Safety descriptions also lack detailed event timing, causality assessment, and participant-level overlap. These reporting limitations restrict what can be concluded about both tolerability and clinical outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer — NCT03263429.
- Registry record last updated 2024-08-30; status last verified 2024-08.
- Results first posted 2024-08-30.
- 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
The registry describes a completed Phase I/II, single-group study of CB-839 with panitumumab and irinotecan in patients with metastatic and refractory RAS wildtype colorectal cancer. It records enrollment of 29 and lists a Phase I dose-finding objective: determining the maximum tolerated dose of CB-839 in mg. The record describes Bayesian continual reassessment, cohorts of 3, and dose levels of 400, 600 and 800mg.
The intervention schedule includes CB-839 and panitumumab, with irinotecan specified for Phase I only. A Phase II dose-expansion group at 800mg is listed. Secondary outcomes include disease control, imaging, plasma exosomal content, progression-free survival, and overall survival. Safety counts are recorded for the dose and phase groups.
The registry record does not report the primary endpoint result, numerical secondary outcome findings, analysis populations, missing-data methods, or a multiplicity plan. Its design and safety descriptions can be summarized, but they do not establish comparative treatment effects or the precision of the study’s outcome estimates.