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 Safety/Efficacy Study of Imprime PGG With Cetuximab in Patients With Recurrent/Progressive Colorectal Carcinoma (NCT00545545), a non-randomized phase 1, phase 2 study. The primary outcome is Safety and Maximum Tolerated Dosage of Imprime PGG When Used in Combination With Cetuximab With or Without Irinotecan Therapy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00545545 |
| Phase | Phase 1, Phase 2 |
| Condition | Recurrent Colorectal Carcinoma, Progressive Colorectal Carcinoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | HiberCell, Inc. |
| Results posted | Yes |
2. Clinical Question
The study examined safety and the maximum tolerated dosage of Imprime PGG when given with cetuximab, either with or without irinotecan, in people with recurrent or progressive colorectal carcinoma after treatment with a 5-fluorouracil-containing regimen. The dose-escalation component considered Imprime PGG doses of 2 mg/kg, 4 mg/kg, and 6 mg/kg. The registry record describes six treatment combinations: each dose with cetuximab and irinotecan, and each dose with cetuximab without irinotecan.
The central statistical question was whether drug-related adverse events meeting the protocol’s dose-limiting toxicity criteria would constrain escalation to higher Imprime PGG doses. The primary endpoint was defined around safety and maximum tolerated dosage, with dose-limiting toxicity assessed during the first 3 weeks of treatment and 1 week follow-up. The registry record also lists tumor response categories, overall response rate, disease control rate, time-to-progression, and durations of response and disease control as secondary outcomes.
The study was non-randomized, so differences across dose groups or between regimens cannot be read as unbiased treatment effects. Its structure is primarily suited to describing safety during dose escalation and identifying a dose for further study, rather than establishing comparative efficacy.
Population
People with recurrent or progressive colorectal carcinoma following treatment with a 5-fluorouracil-containing regimen.
Intervention
Weekly Imprime PGG at 2 mg/kg, 4 mg/kg, or 6 mg/kg with concomitant cetuximab, with or without irinotecan.
Comparator
No randomized control group is described. The registry record identifies non-randomized dose groups and treatment combinations.
Primary question
What safety findings and maximum tolerated dosage were observed for Imprime PGG used with cetuximab, with or without irinotecan?
3. Trial Design
The registry record describes a Phase 1b and Phase 2, multicenter, dose-escalating study. It was non-randomized, had no masking, and used a parallel model. Enrollment was 32. The recorded start was 2007-10, primary completion was 2009-12, and the study status is completed.
Participants were assigned to treatment combinations involving Imprime PGG and cetuximab, either with or without irinotecan. The recorded dose levels were 2 mg/kg, 4 mg/kg, and 6 mg/kg. Imprime PGG was described as administered weekly. This creates dose groups within two treatment settings, rather than a randomized comparison between a study regimen and a control regimen. Because assignment was non-randomized, differences between groups could reflect differences in who entered each group, treatment context, or other factors, as well as any dose or regimen differences.
The primary objective was safety and maximum tolerated dosage. The registry record describes a dose-limiting toxicity decision process: if one of the initial three subjects at a dose experienced a dose-limiting toxicity, three additional subjects were to enter that dose group. If two or more subjects in the expanded group experienced a dose-limiting toxicity, the study was to stop and the maximum tolerated dosage was defined as the dose before the dose at which the toxicity was observed. If a dose-limiting toxicity occurred in the first 2 mg/kg dose group, the protocol allowed the next group to receive 1 mg/kg.
These details describe the planned escalation rules, not the observed dose-limiting toxicity findings. The registry record does not report the resulting maximum tolerated dosage, the number of dose-limiting toxicities by group, or the rationale for the overall enrollment target.
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: A total of 32 participants enrolled, all participants received at least one dose of study treatment.
Overall Study
| Stage | Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 6 mg/kg+ Cetuximab + Irinotecan | Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab |
|---|---|---|---|---|---|---|
| STARTED | 3 | 7 | 0 | 4 | 9 | 9 |
| Discontinued | 3 | 7 | 0 | 4 | 9 | 9 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 7 | 0 | 4 | 9 | 9 |
Reasons for not completing this period:
| Reason | Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 6 mg/kg+ Cetuximab + Irinotecan | Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab |
|---|---|---|---|---|---|---|
| Progressive Neoplastic Disease | 1 | 5 | 0 | 4 | 8 | 7 |
| Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Physician Decision | 1 | 0 | 0 | 0 | 0 | 1 |
| Irinotecan intolerance | 1 | 1 | 0 | 0 | 0 | 0 |
| No target lesions to track post surgery | 0 | 0 | 0 | 0 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The safety population comprised of all subjects who received any amount of Imprime PGG.
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: The safety population comprised all subjects who received any amount of Imprime PGG.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 6 mg/kg+ Cetuximab + Irinotecan | Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 7 | 0 | 4 | 9 | 9 | |
| Age, Continuous | years | 57.0 (SD 6.6) | 52.9 (SD 12.4) | — | 52.0 (SD 10.8) | 52.6 (SD 11.8) | 61.9 (SD 9.3) |
| Sex: Female, Male: Female | Participants | 0 | 3 | 0 | 1 | 4 | 2 |
| Sex: Female, Male: Male | Participants | 3 | 4 | 0 | 3 | 5 | 7 |
| Race/Ethnicity, Customized: East Southeast Asian | participants | 3 | 7 | — | 4 | 9 | 9 |
| Baseline Karnofsky Performance Status Score | units on a scale | 86.7 (SD 15.3) | 92.9 (SD 7.6) | — | 92.5 (SD 5.0) | 90.0 (SD 7.1) | 93.3 (SD 8.7) |
| Baseline Height | cm | 168.3 (SD 4.2) | 162.3 (SD 11.6) | — | 163.3 (SD 7.5) | 161.8 (SD 9.0) | 162.1 (SD 8.5) |
| Baseline Weight | kg | 69.5 (SD 13.1) | 57.0 (SD 15.1) | — | 60.2 (SD 11.5) | 57.6 (SD 11.6) | 63.4 (SD 8.4) |
| Baseline Body Surface Area | m^2 | 1.8 (SD 0.2) | 1.6 (SD 0.3) | — | 1.6 (SD 0.2) | 1.6 (SD 0.2) | 1.7 (SD 0.1) |
| Time Since Initial Tumor Diagnosis | days | 630.7 (SD 560.7) | 686.6 (SD 354.7) | — | 710.5 (SD 507.7) | 776.7 (SD 597.1) | 526.6 (SD 335.8) |
| Initial Pathologic Diagnosis: Colon Carcinoma | participants | 2 | 2 | — | 2 | 5 | 8 |
| Initial Pathologic Diagnosis: Rectum Carcinoma | participants | 1 | 5 | — | 2 | 4 | 1 |
| Basis of Diagnosis: Cytology | participants | 0 | 0 | — | 0 | 1 | 0 |
| Basis of Diagnosis: Histology | participants | 3 | 7 | — | 4 | 8 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Maximum Tolerated Dosage of Imprime PGG When Used in Combination With Cetuximab With or Without Irinotecan Therapy, measured over From the date of the first dose of study drug to disease progression or until development of a drug toxicity that precludes further protocol treatment, up to 15 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns safety and maximum tolerated dosage of Imprime PGG used with cetuximab, with or without irinotecan. The registry record defines the safety population as all subjects who received any amount of Imprime PGG. Dose-limiting toxicity was assessed using drug-related adverse events meeting the stated criteria during the first 3 weeks of treatment and 1 week follow-up. The endpoint timeframe for the broader safety assessment is described as running from the first dose of study drug to disease progression or development of a drug toxicity that precludes further protocol treatment, up to 15 months.
Maximum tolerated dosage is a dose-escalation measure. In general, it helps identify a dose boundary for subsequent evaluation by linking dose increases to prespecified toxicity rules. It is not itself a measure of comparative benefit, and it does not establish how a regimen performs relative to an alternative treatment.
The registry record gives the endpoint definition and escalation rules but does not report the primary endpoint result. It does not state which dose was determined to be the maximum tolerated dosage or provide dose-limiting toxicity counts by dose group. The adverse-event counts that are reported are safety information, but they do not by themselves supply the missing maximum tolerated dosage result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study’s design and some adverse-event counts, but it does not provide a reported primary endpoint result. In particular, it does not state the maximum tolerated dosage or report dose-limiting toxicity counts by dose group. The escalation rules can therefore be described as protocol rules, but they cannot be used to infer which dose was selected or whether escalation stopped for toxicity.
For serious adverse events, the listed safety groups report affected and at-risk counts. In the 2 mg/kg Imprime PGG plus cetuximab plus irinotecan group, 3 of 3 participants were reported with serious adverse events. In the 4 mg/kg combination group, 6 of 7 were reported with serious adverse events. No participants were listed at risk in the 6 mg/kg combination group. In the cetuximab-only treatment setting, the serious adverse-event counts were 2 of 4 at 2 mg/kg, 4 of 9 at 4 mg/kg, and 2 of 9 at 6 mg/kg. These are descriptive counts in a non-randomized study, not comparative estimates adjusted for differences among groups.
Other adverse events were reported for all participants listed at risk in each non-empty safety group: 3 of 3, 7 of 7, 4 of 4, 9 of 9, and 9 of 9, respectively. The 6 mg/kg group with irinotecan had no participants listed at risk. The record also lists serious-event terms with percentages, including neutropenia, diarrhoea, blood amylase increased, and dehydration at 66.7%, and anaemia and gastritis at 33.3%. The record does not give corresponding term counts in the information summarized.
The listed efficacy outcomes include response categories, overall response rate, disease control rate, time-to-progression, and durations of response and disease control. Their results are not reported in the registry record. No statistical analyses are listed. Consequently, the posted information does not support an estimate of treatment efficacy, a randomized treatment contrast, or a precise assessment of uncertainty around the efficacy outcomes.
Planning sample sizes, if presented alongside the results, should be read as illustrations based on an observed effect and stated assumptions, not as observed power or as the original trial’s enrollment justification. The registry record does not report the study’s sample-size justification.
9. Statistical Methods Explained
The most informative statistical reading begins by separating the study’s design, its prespecified decision rule, and its reported results. The record describes a non-randomized dose-escalation study and gives a primary safety objective. It also gives rules for how enrollment at a dose could expand in response to dose-limiting toxicity. Those protocol details explain how decisions were intended to be made, but they are not the results of applying those rules.
What does dose escalation measure?
In general, dose escalation evaluates whether adverse events become unacceptable as dose increases. A dose-limiting toxicity is an event that meets criteria defined by the protocol and is considered in the dose decision. The registry record says the assessment focused on drug-related events in the first 3 weeks of treatment and 1 week follow-up. It sets out an expansion rule following a dose-limiting toxicity and a stopping rule for the expanded group. Such rules make the decision process explicit, but the interpretation still depends on observed event counts and their clinical classification. The actual dose-limiting toxicity findings and selected maximum tolerated dosage are not reported in the registry record.
How should counts be understood?
For binary outcomes, a count of participants with an event is a direct description of how many people in a defined group experienced that event. The at-risk count supplies the group denominator for interpreting that count. These counts are useful for transparency, especially in a small dose-escalation study, but they do not adjust for differences in participant characteristics, exposure, follow-up, or treatment assignment. A count is not by itself a measure of causal effect. The serious adverse-event counts should therefore be read as group-specific descriptions, not as evidence that one regimen caused more or fewer events than another.
Small groups also make observed proportions unstable: a change in the experience of one participant can noticeably alter the reported group proportion. This is a general statistical limitation of sparse data. Confidence intervals can communicate uncertainty around estimates, but the registry record does not report confidence intervals for the adverse-event counts or efficacy outcomes described in the record.
Why does non-random assignment matter?
Random assignment, in general, helps balance measured and unmeasured participant characteristics across treatment groups. This study is recorded as non-randomized, so group composition may differ. In addition, the treatment settings differ by use of irinotecan, and the groups are arranged by dose. A direct comparison between these groups would therefore mix potential dose differences with regimen and participant differences. The registry record itself cautions that the arms are not a like-for-like control comparison. Descriptive results remain useful for documenting what was observed in each group, but they cannot isolate a treatment effect in the way a randomized comparison is designed to do.
How do the planning illustrations differ from observed results?
In general, a sample-size calculation asks how many participants may be needed under specified assumptions to detect a chosen effect with a chosen error rate. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed with those assumptions. The record does not report its own sample-size justification. A planning illustration is not observed power, and it does not replace a trial’s actual outcome estimates or uncertainty intervals.
For time-to-event outcomes, general planning methods use event counts because the information available depends on events rather than enrollment alone. The stated assumptions distinguish total events for time-to-event illustrations from participants per arm for other illustrations. The registry record lists time-to-progression but does not report its result, event count, or analysis details. Therefore, no independent interpretation of a time-to-event effect or its precision can be made from the listed information.
What can be concluded from the analysis record?
The record lists seven outcome measures and zero analyses. This means the posted record does not provide analysis results for the listed outcomes in the information available. It does not establish that no analyses were conducted outside the registry record. For the reader, the practical distinction is that an endpoint name and a planned method do not constitute an outcome estimate. The reported adverse-event counts can be described; efficacy estimates and the primary maximum tolerated dosage conclusion cannot be reconstructed from the stated information.
10. Multiplicity, Missing Data and Analysis Populations
The record lists multiple secondary outcomes, including tumor response categories, overall response rate, disease control rate, time-to-progression, and durations of response and disease control. It also involves several dose groups and treatment combinations. When multiple outcomes or group comparisons are examined, the chance of at least one apparently notable finding can increase. In general, a prespecified outcome hierarchy or multiplicity adjustment can help clarify how multiple statistical tests are interpreted. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or statistical analysis results.
Missing-data handling is not reported in the registry record. The record does not describe how participants with incomplete outcome assessments, interrupted treatment, or unavailable follow-up were handled for efficacy outcomes. It also does not give an analysis population for the secondary outcomes. The primary safety population is defined as all subjects who received any amount of Imprime PGG, but that definition alone does not explain how every endpoint was analyzed.
The registry record’s zero listed analyses means that estimates, uncertainty intervals, and hypothesis tests for the listed outcomes are not reported in the record. It does not establish whether analyses were carried out elsewhere. Without outcome denominators, missingness details, and analysis methods, response and time-to-event results cannot be assessed for completeness or risk of bias. These gaps are distinct from the reported adverse-event counts, which remain descriptive information about the safety groups listed.
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 |
|---|---|---|---|
| Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | 3 | 3 | 100.0% |
| Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | 6 | 7 | 85.7% |
| Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | 2 | 4 | 50.0% |
| Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | 4 | 9 | 44.4% |
| Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab | 2 | 9 | 22.2% |
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 |
|---|---|
| Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | 3 of 3 |
| Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | 7 of 7 |
| Arm 1, Imprime PGG Injection 6 mg/kg+ Cetuximab + Irinotecan | 0 of 0 |
| Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | 4 of 4 |
| Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | 9 of 9 |
| Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab | 9 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 6 mg/kg+ Cetuximab + Irinotecan | Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab |
|---|---|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 3 | 1 of 7 | 0 of 0 | 1 of 4 | 2 of 9 | 1 of 9 |
| Diarrhoea | Gastrointestinal disorders | 2 of 3 | 3 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Neutropenia | Blood and lymphatic system disorders | 2 of 3 | 2 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Dehydration | Metabolism and nutrition disorders | 2 of 3 | 2 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 3 | 2 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | 0 of 3 | 0 of 7 | 0 of 0 | 1 of 4 | 0 of 9 | 1 of 9 |
| Blood amylase increased | Investigations | 2 of 3 | 0 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 3 | 1 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Abdominal pain | Gastrointestinal disorders | 0 of 3 | 1 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
| Gastritis | Gastrointestinal disorders | 1 of 3 | 0 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 0 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan | Arm 1, Imprime PGG Injection 6 mg/kg+ Cetuximab + Irinotecan | Arm 2, Imprime PGG Injection 2 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 4 mg/kg+ Cetuximab | Arm 2, Imprime PGG Injection 6 mg/kg+ Cetuximab |
|---|---|---|---|---|---|---|---|
| Dermatits acneform | Skin and subcutaneous tissue disorders | 1 of 3 | 3 of 7 | 0 of 0 | 3 of 4 | 8 of 9 | 7 of 9 |
| Hypokalaemia | Metabolism and nutrition disorders | 2 of 3 | 6 of 7 | 0 of 0 | 1 of 4 | 7 of 9 | 2 of 9 |
| Gammaglutamyltransferase increased | Investigations | 1 of 3 | 5 of 7 | 0 of 0 | 3 of 4 | 4 of 9 | 4 of 9 |
| Alanine amniotransferase increased | Investigations | 1 of 3 | 4 of 7 | 0 of 0 | 3 of 4 | 5 of 9 | 3 of 9 |
| Asparate amniotransferase increased | Investigations | 0 of 3 | 4 of 7 | 0 of 0 | 2 of 4 | 6 of 9 | 4 of 9 |
| Blood amylase increased | Investigations | 3 of 3 | 5 of 7 | 0 of 0 | 3 of 4 | 2 of 9 | 1 of 9 |
| Blood bilirubin increased | Investigations | 1 of 3 | 3 of 7 | 0 of 0 | 3 of 4 | 3 of 9 | 4 of 9 |
| Dry skin | Skin and subcutaneous tissue disorders | 2 of 3 | 3 of 7 | 0 of 0 | 0 of 4 | 6 of 9 | 2 of 9 |
| Diarrhoea | Gastrointestinal disorders | 3 of 3 | 6 of 7 | 0 of 0 | 0 of 4 | 0 of 9 | 2 of 9 |
| Blood alkaline phosphatase increased | Investigations | 0 of 3 | 2 of 7 | 0 of 0 | 3 of 4 | 3 of 9 | 3 of 9 |
Serious events with the highest arm-level rate: neutropenia (66.7%), diarrhoea (66.7%), blood amylase increased (66.7%), dehydration (66.7%), anaemia (33.3%).
The serious adverse-event figures give the number of participants affected and the number at risk in each named group. The counts are 3 of 3 for Imprime PGG 2 mg/kg with cetuximab and irinotecan; 6 of 7 for 4 mg/kg with cetuximab and irinotecan; 2 of 4 for 2 mg/kg with cetuximab; 4 of 9 for 4 mg/kg with cetuximab; and 2 of 9 for 6 mg/kg with cetuximab. The 6 mg/kg group with irinotecan lists zero participants at risk and zero affected, so it does not provide an exposed group denominator for interpreting event frequency.
The record lists neutropenia, diarrhoea, blood amylase increased, and dehydration at 66.7% among top serious-event terms, and anaemia and gastritis at 33.3%. These percentages are reported as listed; the corresponding term counts are not reported in the registry record. Death counts are also not reported in the registry record.
These safety figures are descriptive, and the group sizes are limited. They do not establish that differences across groups are caused by dose or by the presence or absence of irinotecan. Serious adverse events are not necessarily the same as dose-limiting toxicities: the registry record gives a separate dose-limiting toxicity definition and assessment window, but does not report those endpoint results.
12. What the Result Does, and Does Not, Mean
The record describes a completed, non-randomized dose-escalation study of Imprime PGG with cetuximab, with or without irinotecan, in people with recurrent or progressive colorectal carcinoma following a 5-fluorouracil-containing regimen. It records enrollment of 32 and provides safety-group counts for serious and other adverse events. It also lists several tumor-response and time-to-event outcomes.
What the posted results do not establish is the primary endpoint conclusion. The registry record does not report the maximum tolerated dosage, the number of dose-limiting toxicities by dose, or the resulting escalation decision. It also does not report results for the listed efficacy outcomes. Consequently, the record cannot support a conclusion about the size or precision of a tumor-response or time-to-event effect.
The adverse-event counts should not be interpreted as treatment comparisons. Assignment was non-randomized, and the treatment groups differ in dose and in whether irinotecan was included. Those features prevent a like-for-like comparison. The counts document what was recorded among the participants listed in each group; they do not establish why an event occurred or what would have happened under another regimen.
Any planning sample-size illustrations are separate from trial outcomes. In general, they describe sample sizes under assumptions about an effect and statistical method. They are not observed power and do not show that the trial had a particular chance of detecting a clinical effect. The registry record does not report the original sample-size justification. The most defensible interpretation is therefore bounded: the registry provides study-design details and selected adverse-event counts, while the primary safety conclusion and efficacy estimates are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how a dose-escalation objective differs from a comparative efficacy question. The primary aim was safety and maximum tolerated dosage, with a defined dose-limiting toxicity window and an escalation rule. Those design features identify the evidence the study was intended to generate: observations that guide dose decisions under the stated rules.
The non-randomized, parallel structure also matters for interpretation. A dose group is not automatically a control group, and the combinations with and without irinotecan are not described as randomized alternatives. The registry record explicitly notes that the arms are not a like-for-like control comparison. Thus, the adverse-event counts are best treated as descriptive safety information rather than as estimates of comparative treatment effects.
The record also illustrates why outcome definitions and outcome results must be distinguished. A list of secondary outcomes shows what was measured or intended for assessment, but does not provide response rates or time-to-event estimates. Likewise, a dose-escalation rule explains how the maximum tolerated dosage would be determined, but does not reveal the dose selected. The analyses are not reported in the registry record, so the statistical evidence for the listed efficacy outcomes cannot be evaluated from this record.
Finally, sparse group counts call for careful attention to uncertainty. Counts remain useful and transparent, but small groups provide limited precision and do not justify broad comparisons. The design, endpoint rules, and reported counts can be described; unreported efficacy results and dose decisions should remain unresolved rather than inferred.
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 main trial-specific limitation is that the registry record does not report the primary endpoint result. Although it defines dose-limiting toxicity, describes the escalation rules, and identifies the safety population, it does not give dose-limiting toxicity counts or state the maximum tolerated dosage. The protocol’s decision process therefore cannot be connected to an observed dose decision from the registry record.
The record also does not report the results of its listed secondary outcomes. Tumor-response categories, overall response rate, disease control rate, time-to-progression, and durations of response and disease control are named, but their estimates are not reported in the registry record. No analyses are listed, and uncertainty intervals and statistical tests are not reported.
Non-randomized assignment limits comparison across the dose and regimen groups. The combinations differ by dose and by whether irinotecan was included, so observed group differences would not isolate one treatment component. Some safety groups have small denominators, and the 6 mg/kg group with irinotecan has no participants listed at risk. Death counts are not reported in the registry record.
Further details that would help assess the results, including missing-data handling for efficacy outcomes, analysis populations beyond the stated safety population, multiplicity procedures, and the study’s sample-size justification, are not reported in the registry record. These limitations mean the posted record can support a design description and a cautious account of listed adverse-event counts, but not a complete assessment of the trial’s primary or efficacy conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety/Efficacy Study of Imprime PGG With Cetuximab in Patients With Recurrent/Progressive Colorectal Carcinoma — NCT00545545.
- Registry record last updated 2025-03-19; status last verified 2025-03.
- Results first posted 2025-03-19.
- 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 record describes a completed multicenter Phase 1b and Phase 2, non-randomized, unmasked, parallel dose-escalation study with enrollment of 32. It evaluated Imprime PGG at 2 mg/kg, 4 mg/kg, and 6 mg/kg with cetuximab, with or without irinotecan, in recurrent or progressive colorectal carcinoma following a 5-fluorouracil-containing regimen.
The primary endpoint was safety and maximum tolerated dosage, assessed using drug-related dose-limiting toxicities and stated escalation rules. The registry record reports safety-group adverse-event counts, but does not report the maximum tolerated dosage, dose-limiting toxicity counts, or results for the listed efficacy outcomes. Analyses, missing-data methods, multiplicity procedures, and the original sample-size justification are not reported in the registry record.