AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors (NCT00427349), a na phase 2 study. The primary outcome is Four-month Progression-free Survival Rate.

2. Clinical Question

Statistically, this is a question about the frequency of remaining progression free at a specified time in a treated group, rather than a comparison of outcomes between treatment assignments. A single-group rate can describe the outcome observed under the study conditions, but it cannot by itself estimate how that outcome differs from what would have occurred in a control group.

3. Trial Design

The registry record describes a phase II clinical and biologic study of AMG 706 and octreotide in patients with low-grade neuroendocrine tumors. It lists the study as completed, with enrollment of 46 and the Eastern Cooperative Oncology Group as sponsor. The study model is single-group; allocation is listed as not applicable, and masking as none. These design features mean that the primary result is intended to describe outcomes in the treated group, not a randomized comparison between treatments.

The arm description states that patients received oral AMG 706 and octreotide acetate intramuscularly once daily on days 1-28. Treatment was to repeat every 28 days in the absence of disease progression or unacceptable toxicity. The registry text says AMG 706 was administered on a flat scale in mg/day rather than by weight or body surface area, but the dose itself is not reported in the registry record. The arm description ends mid-sentence after this dosing information, so further details of the regimen are not reported in the registry record.

Enrollment and endpoint-analysis populations should not be treated as interchangeable. The overall enrollment is 46. The primary endpoint description says the analysis population includes all 44 eligible and treated patients, but also says that 2 patients without a disease assessment after study entry are excluded from the analysis. The actual denominator used for the reported endpoint is not stated in the available result information. The endpoint estimate and confidence interval are also not reported in the registry record.

The registry lists overall survival and objective response rate as secondary outcomes. It does not report a control arm, randomization, or masking. Consequently, a difference between this group’s outcome and an outcome from another study would not be a randomized treatment contrast. Differences in participants, eligibility, assessment, follow-up, or other features could contribute to such a comparison, and those factors cannot be separated from treatment effects using this design alone.

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: The analysis population includes all 44 eligible and treated patients. But 2 patients did not have disease assessment after study entry and are excluded from the analysis.

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: Per protocol, the primary population for all efficacy analysis is all eligible and treated patients

6. Primary Endpoint

The registry lists the primary outcome as Four-month Progression-free Survival Rate, measured over assessed every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four.

The primary endpoint is the four-month progression-free survival rate, expressed as a percentage of participants. It is intended to describe the proportion of the specified study population who remain free of disease progression at four months after study entry. The registry says progression was assessed using Response Evaluation Criteria in Solid Tumors, version 1.0, or RECIST 1.0.

The record defines progression as at least a 20% increase in the sum of the longest diameters of target lesions, using the smallest recorded sum since baseline as the reference. It also includes the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. These criteria provide an operational rule for classifying progression rather than relying only on an unstructured clinical impression.

A fixed-time progression-free survival rate is useful because it communicates the proportion of a defined population who have not met the progression definition by a clinically specified time. It is a proportion at a landmark, not a description of how long each participant remained progression free across the entire follow-up period. Interpretation depends on the population included, whether disease status was assessed, and how participants without an assessment were handled.

The registry describes assessments every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four. It does not report the observed four-month rate or its 90% confidence interval. Thus the endpoint definition and assessment schedule are available, but the numerical result needed to describe the observed outcome is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical quantity in this study is a proportion: the number of participants meeting the endpoint condition at four months relative to the analysis population specified for the endpoint. The registry defines progression-free status through the absence of progression by that time, using RECIST 1.0. This is a binary outcome for each participant at the specified time: progression free or not classified as progression free. The corresponding group-level rate summarizes those individual classifications.

What does the endpoint rate represent?

A fixed-time rate answers a focused question about status at a landmark. It differs from a time-to-event analysis that uses the timing of progression or death throughout follow-up. The registry’s endpoint is explicitly the four-month progression-free survival rate, not a median duration of progression-free survival. The record does not give a median or another time-to-event summary, and such a result is not reported in the registry record.

For an endpoint rate to be interpretable, the numerator and denominator need to be clear. The endpoint description says the rate is the number of patients still progression free at four months divided by the number of eligible and treated patients enrolled. Its population note then says the analysis population includes all 44 eligible and treated patients but excludes 2 patients who had no disease assessment after study entry. The actual number included in the reported calculation is not stated in the available result information. It would be inappropriate to infer a denominator by subtracting the excluded participants from the stated analysis population or by using the enrollment figure, because the record does not specify which denominator was used for the endpoint result.

How should the confidence interval be read?

The endpoint specifies a 90% confidence interval. In general, a confidence interval expresses sampling uncertainty around an estimate under the method used to construct it. It helps distinguish a relatively precise estimate from one that is compatible with a broader range of underlying rates. A confidence interval is not a guarantee about the outcome of any particular participant, and it does not correct for bias in the study design, missing observations, or an unclear denominator. The interval’s endpoints and construction method are not reported in the registry record, so its width and assumptions cannot be assessed.

A proportion is commonly estimated from binary participant outcomes. In general, the uncertainty around such an estimate is affected by the number of observations and by how close the observed rate is to the extremes of its possible range. This is a general statistical point, not a calculation for this study. Without the observed count and denominator, no rate or uncertainty measure can be reconstructed from the registry information in this record.

What role does the progression definition play?

RECIST 1.0 supplies rules for deciding whether the measured disease has progressed. The registry describes progression as at least a 20% increase in the sum of the longest diameters of target lesions, referenced to the smallest sum recorded since baseline, or the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Applying a defined rule can improve consistency in outcome classification. It does not by itself show that every participant had an assessment at the required time or establish how unassessed participants should be classified. The registry does not report details of review procedures, assessment adjudication, or handling of missing disease assessments beyond noting the exclusions.

The stated schedule was assessment every 4 weeks while on treatment and at three months post-treatment for participants treated for one cycle, up to month four. A schedule describes when assessments were intended; it is not evidence that every scheduled assessment was completed. The registry record does not report assessment completion by participant or describe the timing of any deviations.

What does a single-group design allow?

In general, an uncontrolled study can estimate outcomes observed among participants receiving the study regimen. It cannot isolate a treatment effect from the natural course of disease, selection into the study, other care, or other influences on outcome. Here, allocation is listed as not applicable and the model is single-group. There is no concurrent control group against which to estimate a between-group contrast. The registry lists masking as none, but does not describe whether endpoint assessments had any independent review.

The registry’s sample-size assumptions describe a planning illustration computed from the observed effect, using 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. These are assumptions for a planning illustration, not the design of this single-group study; in particular, equal allocation between two arms does not describe the registered trial model. The numerical planning outputs are not reported in the registry record. Such illustrations should be interpreted as hypothetical planning quantities, not as observed power or as a sample-size justification for this trial.

In general, power is a property of a design under specified assumptions about the effect, variability, analysis, and decision threshold. It is not a measure of the probability that a completed study’s conclusion is correct. A planning calculation based on an observed effect is especially dependent on that effect estimate and does not replace a documented prospective design rationale. The registry record does not report the trial’s sample-size justification or a statistical analysis plan.

The record lists 3 outcome measures and 1 analysis, but does not describe the analysis methods in enough detail to identify a model, a test, or an adjustment procedure. The primary endpoint is a percentage, and its uncertainty is described by a 90% confidence interval. The method used to calculate that interval is not reported in the registry record. Accordingly, the available description supports explaining the intended estimand and endpoint definition, but not reproducing or independently verifying the analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("AMG 706+Octreotide")
n      <- c(42)
events <- c(33)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  AMG 706+Octreotide  42  33  78.6  63.2  89.7  64.1  88.3  64.0  88.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the four-month progression-free survival rate as the primary outcome and overall survival and objective response rate as secondary outcomes. It also lists 3 outcome measures and 1 analysis. These entries show that more than one outcome was considered, but they do not specify whether formal hypothesis tests were performed for each outcome or how any multiplicity was handled. An adjustment strategy, hierarchy of testing, or other method for controlling the interpretation of multiple outcomes is not reported in the registry record.

The primary endpoint description identifies 44 eligible and treated patients in the analysis population and says that 2 participants without a post-entry disease assessment were excluded. It does not state the actual denominator used for the endpoint calculation. The registry’s endpoint definition refers to eligible and treated patients enrolled, while the population note describes exclusions for missing disease assessment. Without the endpoint count, denominator, and a fuller account of missing outcome handling, the impact of those exclusions cannot be evaluated.

In general, excluding participants with unavailable outcome data can affect an estimate if those participants differ in outcome from those assessed. This is a general statistical concern, not a claim about the excluded patients in this study. The record does not report a sensitivity analysis, imputation method, or alternative analysis population. It also does not report an intention-to-treat analysis plan or other prespecified population definitions.

The sample-size rationale, interim analysis plan, and full statistical analysis plan are not reported in the registry record. The record’s description of planning assumptions is not evidence of the trial’s own prospective design calculation. As a result, the analysis population, missing-data approach, multiplicity handling, and prespecification of analyses cannot be fully assessed from the registry information.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertension (26.7%), fatigue (13.3%), cholecystitis (11.1%), diarrhea (8.9%), abdominal pain (8.9%).

The registry reports one treatment group for adverse events, labelled MG 706+Octreotide. For serious adverse events, it lists 45 participants at risk and 26 affected. For other adverse events, it lists 45 at risk and 43 affected. These are separate registry counts and should be read within their stated categories. The record does not explain why the adverse-event group counts at risk differ from the enrollment or primary endpoint population counts.

The listed serious adverse event terms and percentages are hypertension, 26.7%; fatigue, 13.3%; cholecystitis, 11.1%; diarrhea, 8.9%; abdominal pain, 8.9%; and platelet count decreased, 6.7%. These percentages describe the listed terms in the registry record. The information available does not state whether participants could contribute to more than one term, nor does it provide a complete event-level account or severity distribution for these entries.

In general, an adverse event is an event recorded during a study and is not, by that fact alone, proof that treatment caused it. With no comparator group, these figures describe events in the treated group and do not provide a comparative estimate of excess risk. The registry does not report deaths in the adverse-event data. The safety counts do not determine the progression-free survival result, which is not reported in the registry record.

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

The registry establishes that this completed phase II study examined AMG 706 with octreotide in a single group of patients with low-grade neuroendocrine tumors. It defines four-month progression-free survival using RECIST 1.0 and specifies a 90% confidence interval for the percentage endpoint. However, the observed rate and interval are not reported in the registry record. The principal outcome therefore cannot be described quantitatively from this information.

Even if the endpoint estimate were available, its meaning would be descriptive of the study population and follow-up conditions. Because there was no control group, the study cannot by itself show how the outcome compares with no study treatment or another treatment. A comparison with results from a separate population would be vulnerable to differences in eligibility, baseline characteristics, follow-up, assessment, and other aspects of care. The record does not supply a randomized contrast that could address those differences.

The endpoint definition uses explicit progression criteria, which helps explain what counted as an event. Interpretation also depends on the analysis population and completeness of assessment. The registry describes 44 eligible and treated participants and 2 exclusions for no disease assessment after study entry, but does not identify the actual denominator used to calculate the endpoint result. This uncertainty about the analyzed population adds to the absence of the estimate itself.

The listed serious adverse event counts and terms provide a separate description of safety reporting in the treated group. They do not establish causation, quantify comparative risk, or resolve the missing primary outcome. Overall survival and objective response rate are listed as secondary outcomes, but their numerical results are not reported in the registry record.

Accordingly, the record supports a description of the study question, design, endpoint definition, assessment schedule, and selected safety figures. It does not support a conclusion about the observed four-month progression-free survival rate, the precision of that estimate, or a comparative treatment effect. Those questions require outcome results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically instructive because its primary endpoint is clearly defined while the numerical endpoint result is not reported in the registry record. That distinction matters: a detailed definition tells readers what was intended to be measured, but it cannot substitute for the estimate, denominator, and confidence interval needed to understand what was observed.

The record also illustrates why population descriptions need to be read carefully. Enrollment is 46, while the endpoint description identifies 44 eligible and treated patients and notes that 2 without a post-entry disease assessment were excluded. The endpoint definition and population note do not make the actual calculation denominator clear. In a rate analysis, that detail is essential because the denominator determines the population to which the percentage refers.

The single-group design provides a further statistical lesson. Descriptive outcomes in a treated group can be useful, but they do not supply the treatment contrast available from a randomized control group. A strong-looking rate, if reported, would still need interpretation in light of selection, disease course, assessment, and other influences. The registry identifies no like-for-like control comparison.

Finally, the record distinguishes an endpoint from secondary outcomes and includes safety figures, while leaving important analysis details unreported. The sample-size assumptions describe a planning illustration with equal allocation between two arms, although the registered study is single-group. That mismatch is a reminder that hypothetical planning assumptions should not be mistaken for the actual design or its observed performance. Taken together, these features show how design, denominator clarity, outcome availability, and analysis transparency shape what readers can conclude.

15. 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 primary limitation for interpreting efficacy is that the observed four-month progression-free survival rate and its 90% confidence interval are not reported in the registry record. The endpoint is defined, but the result itself cannot be characterized. The registry also does not report the endpoint count or the denominator used in the calculation.

The population information leaves an ambiguity. The record says the analysis population includes 44 eligible and treated patients, then says 2 patients without disease assessment after study entry were excluded. It does not reconcile this description with the endpoint definition’s reference to eligible and treated patients enrolled. The actual analyzed population and treatment of missing assessments cannot be established from the record.

The single-group design has no concurrent control and does not support a randomized comparison. Allocation is not applicable and masking is listed as none. The registry does not report whether endpoint assessments received independent review, how departures from the assessment schedule were handled, or whether analyses accounted for censoring or other incomplete follow-up.

The statistical analysis plan, sample-size justification, interim analysis details, and multiplicity approach are not reported in the registry record. Secondary outcome results for overall survival and objective response rate are also not reported. The sample-size assumptions describe a planning illustration using equal allocation between two arms, which does not match this single-group design; numerical planning outputs are not included in the record.

The safety information is limited to counts and selected serious adverse event terms with percentages. The registry does not report deaths in these data and does not provide a comparator for interpreting event frequency. These limitations restrict both outcome interpretation and assessment of how completely the study’s results are reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors — NCT00427349.
• Registry record last updated 2023-07-05; status last verified 2023-06.
• Results first posted 2015-06-04.
• 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.

19. Record Summary

The registry record describes a completed phase II, single-group study of AMG 706 and octreotide in patients with low-grade neuroendocrine tumors. Enrollment was 46, and the sponsor was the Eastern Cooperative Oncology Group. The study start date is 2008-11-07, and primary completion is listed as 2014-10.

The primary outcome was the four-month progression-free survival rate, assessed using RECIST 1.0 and accompanied by a specified 90% confidence interval. The record describes an analysis population of 44 eligible and treated patients and notes that 2 participants without a post-entry disease assessment were excluded. The observed endpoint estimate, interval, and actual analysis denominator are not reported in the registry record.

Overall survival and objective response rate are listed as secondary outcomes. The record also lists serious adverse event counts and selected terms. With no control group, the study describes outcomes in the treated group rather than a randomized comparison. Further statistical analysis details, including the analysis plan and multiplicity handling, are not reported in the registry record.