ECI301 and Radiation for Advanced or Metastatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ECI301 and Radiation for Advanced or Metastatic Cancer (NCT01441115), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of ECI301 Delivered in Combination With 30 Gray (Gy) External Beam Radiation to Participants With Metastatic or Locally Advanced Cancer.

2. Clinical Question

3. Trial Design

This was a phase I, open-label, single-group trial of ECI301 in combination with radiation for people with advanced or metastatic cancer. It was sponsored by the National Cancer Institute (NCI). The registry record lists a start date of 2011-09-06, primary completion on 2013-04-24, and a terminated status. Enrollment was two participants. These details establish the scale and status of the study, but do not establish that every planned procedure or assessment was completed for each participant.

The treatment plan described radiation five days a week for two weeks. ECI301 was to be given intravenously during the second week of radiation, with different doses used to assess safety and effectiveness. The listed arm is dose level 1, 25 ug/kg, with radiation. The summary also describes frequent blood tests and imaging, possible tumor sampling at a radiated site and a site that had not received radiation, and follow-up visits. The record does not report which of these procedures were completed for the enrolled participants.

There was no random allocation, masking, or concurrent comparison group. Thus, the design was intended to assess dose and safety in a small early-phase setting, rather than estimate a comparative treatment effect. Secondary outcomes listed in the registry include adverse events, immune responses, pharmacologic parameters, and response at radiated and distant sites. The record does not post statistical analyses for these outcomes. It explains that the study closed after a duplicate trial testing the primary endpoint was initiated in Japan in 2012. The registry record does not report the dose-escalation method or a sample-size justification.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This MTD was not found because the trial was terminated early. A trial using ECI301 \& radiation was initiated in Japan in 2012. This tested the primary endpoint in a duplicate trial, thus the study was closed. In addition, as specified in the protocol, the number of participants required to complete this trial involves 5 cohorts of 3 to 6 participants.

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.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of ECI301 Delivered in Combination With 30 Gray (Gy) External Beam Radiation to Participants With Metastatic or Locally Advanced Cancer, measured over During treatment or the first three weeks after treatment.

The primary endpoint was the maximum tolerated dose (MTD) of ECI301 administered with 30 Gray (Gy) of external beam radiation. The registry defines MTD using dose-limiting toxicity (DLT) during treatment or the first three weeks after treatment. In its definition, the MTD is the highest dose level at which no more than one of six participants has a DLT, with at least two of up to six participants experiencing DLT at the next dose level. The record lists examples of DLT: any grade 3 or greater non-hematologic toxicity, grade 3 neutropenia or thrombocytopenia, any grade 4 anemia, and toxicity requiring a cumulative radiation treatment delay of four or more days.

In general, early-phase dose-finding studies use an endpoint such as MTD to guide selection of a dose for further study while monitoring treatment-limiting toxicity. The endpoint is not itself a measure of comparative efficacy. Its interpretation depends on observing toxicity at the dose levels tested and on the dose-escalation procedure. The registry record states that the MTD was not found because the trial was terminated early. It does not report a dose-level toxicity analysis or identify an established MTD for this combination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint determine what statistical conclusions are possible. This study was single-group and unmasked, with allocation listed as not applicable. In general, a single-group study describes outcomes among participants receiving the study regimen; it does not directly estimate a difference between that regimen and a concurrent control. The posted record does not report a statistical analysis plan, so no particular model or testing procedure can be attributed to the investigators.

How to read the dose-finding endpoint

The primary endpoint is a threshold-selection question, not a comparison of average outcomes. The registry defines MTD through observed DLTs at successive dose levels: the selected level must meet the stated toxicity condition, while a higher level must meet the stated DLT condition. This kind of rule depends on how participants are assigned to dose levels, which levels are tested, and how toxicity is assessed over the specified period. The registry record does not report the escalation algorithm, the number of participants treated at each dose, or a complete account of DLT observations. Since it explicitly says MTD was not found, the rule did not yield a reported dose selection in this trial.

What a confidence interval would mean

In general, a confidence interval describes the range of estimates compatible with the data under a stated statistical method. It communicates precision as well as the direction and scale of an estimate. No confidence interval for the MTD or for a treatment-response outcome is posted in the registry record. Without an endpoint estimate and its analysis method, there is no trial-specific interval to interpret. A confidence interval should not be inferred from the enrollment count or from safety counts alone.

What a p-value would mean

In general, a p-value evaluates how unusual data would be under a specified null hypothesis and statistical model. It does not measure the probability that a treatment works, and it does not describe the size or clinical importance of an effect. The registry record posts no statistical analyses, test statistics, or p-values for this study. In addition, a single-group study without a stated comparator would require a clearly defined reference or hypothesis before a comparative p-value could be interpreted.

Why the sample-size illustrations are not trial results

Planning illustrations use assumptions to show the sample size that might be needed for a future comparison. The assumptions described for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. Those are planning assumptions, not a description of this trial's single-group design. The registry record does not post a treatment-effect estimate to serve as the basis for an effect-size interpretation, nor does it report a randomized two-arm comparison. A planning calculation is not observed power and cannot recover a missing analysis or demonstrate that the study had a particular probability of detecting an effect.

In general, power is a design property calculated under specified assumptions about the effect, variability, analysis, and sample size. It is not a measure of whether a completed study's findings are true. With no posted primary endpoint analysis and an early termination, a retrospective claim of observed power would be especially uninformative. Sample-size illustrations should be read as hypothetical planning aids, not evidence about what this trial demonstrated.

Multiplicity and multiple outcomes

The registry lists a primary dose-finding endpoint and secondary outcomes covering adverse events, immune responses, pharmacologic parameters, and responses at radiated and distant sites. When several outcomes or tests are examined, general statistical practice considers multiplicity: the chance of at least one apparently notable result can rise as the number of analyses increases. Methods to address this may include prespecifying a primary outcome, adjusting significance thresholds, or treating secondary analyses as exploratory. The statistical plan and any multiplicity approach are not reported in the registry record. Since no analyses are posted, there are no reported tests to evaluate for multiplicity adjustment.

Small samples also limit precision. In general, estimates based on few observations can vary substantially with the outcome of an individual participant. That is relevant to a study with two participants enrolled, but the registry does not provide participant-level results from which to estimate variability. No numerical precision estimate should be inferred from the enrollment count alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint, the maximum tolerated dose of ECI301 with radiation, and secondary outcomes related to adverse events, immune responses, pharmacologic parameters, and response at radiated and distant sites. Listing several outcomes does not establish which statistical tests were planned, whether any secondary outcome was designated as confirmatory, or whether the investigators adjusted for multiple comparisons. Those details are not reported in the registry record. No statistical analyses are posted, so there are no reported p-values or confidence intervals for which to assess multiplicity handling.

Missing-data procedures and analysis populations are also not described. The registry record does not say how participants with incomplete treatment, unavailable assessments, or early withdrawal would be included in an analysis. It does not identify an intention-to-treat, safety, or evaluable population for the primary endpoint. Although two participants were enrolled, the record does not explain how many were included in each outcome assessment or why the adverse-event at-risk counts are one.

Early termination further limits interpretation because the primary endpoint was not established and the record states that the protocol-required participant number was not reached. The protocol's planned number and its justification are not reported in the registry record. It is therefore not possible to distinguish the implications of the small enrollment from any planned analysis decisions, or to evaluate whether missing observations might have affected the endpoint. These absences should be treated as unknowns, not as evidence that data were complete or that a particular analysis population was used.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summary lists the ECI301 dose level 1, 25 ug/kg, and radiation group. For serious adverse events, one participant was at risk and zero were reported as affected. For other adverse events, one participant was at risk and one was affected. The summary reports zero deaths. No serious adverse-event terms are listed.

These are small descriptive counts, not comparative safety estimates. The registry reports two participants enrolled overall, while the at-risk denominator is one for each adverse-event category. It does not explain the difference or state whether the same participant was included in both categories. The figures should therefore be read using their listed denominators, rather than treated as complete outcomes for all enrolled participants.

The record does not provide event narratives, timing, duration, severity details for the non-serious category, or attribution beyond what is reflected in its outcome descriptions. A zero serious-event count in one participant at risk does not establish that serious toxicity is absent or rule out uncommon harms. Likewise, the report of one participant with other adverse events does not show that ECI301 caused those events. The study has no concurrent control group, and these sparse counts cannot support a comparative risk estimate.

12. What the Result Does, and Does Not, Mean

The registry record shows that a phase I study of ECI301 with radiation was initiated, enrolled two participants, and was terminated before an MTD was found. It describes a dose-finding objective, the toxicity window, and examples of events that would count as DLT. It also reports limited adverse-event counts. These registry entries describe the study and its posted results, but they do not establish a recommended dose or a comparative treatment effect.

The record does not report results for the listed secondary outcomes, including immune responses, pharmacologic parameters, or response at radiated and distant sites. Their inclusion in the registry does not show that a response occurred or that an effect was attributable to ECI301. Because there was no control group, even a reported change in a participant would not, by itself, distinguish the contribution of ECI301 from radiation or other factors.

The adverse-event counts should not be generalized beyond the small at-risk group described in the record. A count of zero serious adverse events among one participant at risk is not evidence that the regimen is free of serious risks. The other adverse-event count is also descriptive and does not establish causation. No statistical uncertainty estimates are posted.

The stated reason for termination was that a duplicate trial testing the primary endpoint had been initiated in Japan in 2012, together with the fact that the protocol-required number of participants had not been reached. This context explains why the trial did not complete its dose-finding objective, but does not substitute for the missing MTD result. The record does not report findings from the other trial.

In general, an early-phase study can provide information about feasibility and toxicity at tested doses, but conclusions depend on adequate exposure and systematic outcome reporting. In this record, enrollment was limited and the primary endpoint was not found. The sound interpretation is therefore descriptive: the trial was terminated early, and its posted results do not resolve the dose-finding question or establish efficacy.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a protocol objective and an answer supported by posted data. The stated primary objective was to find an MTD, using a defined toxicity window and DLT criteria. Yet the registry explicitly says that no MTD was found because the trial terminated early. A clearly defined endpoint does not guarantee that the study will produce an estimate of that endpoint; completion of the planned dose-finding process and reporting of dose-specific observations are also needed.

The study also shows why enrollment and analysis denominators should be read separately. Two participants were enrolled, while the safety summary lists one participant at risk in each reported adverse-event category. Without an explanation of those denominators, the counts cannot be casually translated into a description of all enrolled participants. Statistical interpretation depends not only on the headline enrollment but also on who contributed data to each outcome.

Its single-group design is another useful example. Without a concurrent control, outcomes cannot establish a treatment contrast. This matters for both efficacy questions and attribution of adverse events. Listing response at radiated and distant sites as a secondary outcome does not resolve the lack of a comparison group, particularly when results are not reported.

Finally, closure following initiation of a duplicate trial in Japan underscores that trial termination and endpoint achievement are separate events. The reason for closing the study is documented, but the record still does not report an MTD or statistical analyses. For biostatisticians and clinical researchers, this is a reminder to separate design intent, conduct status, denominators, and posted outcome evidence when interpreting an early-phase record.

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 consequential trial-specific limitation is early termination before the MTD was found. The registry says a duplicate trial testing the primary endpoint was initiated in Japan in 2012, and that the study was closed. It also indicates that the number of participants required by the protocol was not reached, but the available description is incomplete. The planned number of participants and its justification are not reported in the registry record.

Enrollment was two participants, and the only listed arm is dose level 1, 25 ug/kg, with radiation. The record does not give the number treated at each dose, a dose-escalation sequence, or dose-specific DLT observations. Those omissions prevent reconstruction of the dose-finding process. The record also does not establish whether both enrolled participants completed the planned treatment or endpoint assessments.

There was no randomized or concurrent control group, and the study was unmasked. Therefore, the design cannot estimate a treatment difference against another regimen or isolate the effects of ECI301 from radiation and other influences. This is a design limitation, not a statistical adjustment that can be resolved using the posted record.

Results for the secondary outcomes are not reported in the registry record. The adverse-event summary provides only limited counts and uses an at-risk denominator of one for each category, with no explanation of the difference from total enrollment. Participant characteristics, outcome-level missingness, analysis populations, statistical methods, and multiplicity handling are also not reported in the registry record. These gaps restrict assessment of precision, completeness, and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ECI301 and Radiation for Advanced or Metastatic Cancer — NCT01441115.
• Registry record last updated 2021-12-28; status last verified 2021-11.
• Results first posted 2021-12-28.
• 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.

18. Record Summary

NCT01441115 is a phase I, single-group, unmasked study of ECI301 with radiation for advanced or metastatic cancer. The National Cancer Institute (NCI) is listed as sponsor. The registry reports two participants enrolled, a start date of 2011-09-06, primary completion on 2013-04-24, and terminated status.

The primary endpoint was the maximum tolerated dose of ECI301 with 30 Gray (Gy) of external beam radiation, assessed using dose-limiting toxicity during treatment or the first three weeks after treatment. The registry states that the MTD was not found because the study ended early. It cites the initiation of a duplicate trial in Japan in 2012 as the reason for closure.

The record lists secondary outcomes but posts no statistical analyses. The adverse-event summary reports one participant at risk and zero affected for serious adverse events, one at risk and one affected for other adverse events, and zero deaths. These counts are descriptive and do not establish comparative safety or efficacy.