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 Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors (NCT04234568), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of Triapine and Recommended Phase 2 Dose (RP2D).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04234568 |
| Phase | Phase 1 |
| Condition | Metastatic Digestive System Neuroendocrine Neoplasm, Metastatic Neuroendocrine Tumor |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns patients with well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. The listed conditions include metastatic digestive system neuroendocrine neoplasm and metastatic neuroendocrine tumor. The registry record does not provide further eligibility details in the information summarized for this analysis.
Intervention
Participants receive triapine together with lutetium Lu 177 dotatate. The listed regimen gives lutetium Lu 177 dotatate intravenously on day 1 of each cycle and triapine orally on days 1 through 14. Cycles repeat every 56 days for up to 4 cycles, unless disease progresses or toxicity is unacceptable.
Comparator
There is no separate comparator group. The trial is single-group, with no masking and no randomized allocation. Dose levels and escalation or expansion phases are parts of the study design, not like-for-like control groups. Differences between those groups therefore should not be read as randomized treatment effects.
Primary question
The primary question is about dose finding: what is the maximum tolerated dose of triapine with lutetium Lu 177 dotatate, and what dose should be recommended for a phase 2 study? The registry record says these doses will be estimated from observed dose-limiting toxicity. It does not report the resulting dose estimate. Overall response rate, progression-free survival, and overall survival are listed as secondary outcomes, but their results are not reported in the registry record.
3. Trial Design
This is a phase I, single-group study sponsored by the National Cancer Institute. The registry record lists enrollment of 31 and describes escalation and expansion phases. Participants receive the drug combination; there is no randomized comparator and no masking. The escalation and expansion dose groups can describe safety at the listed dose levels, but they are not independent control groups designed for a treatment-effect comparison.
The regimen combines lutetium Lu 177 dotatate, administered intravenously on day 1, with oral triapine on days 1 through 14. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. The listed procedures include computed tomography or magnetic resonance imaging and biospecimen collection. The registry record does not report further operational details about how these procedures inform dose decisions.
The primary outcome is the maximum tolerated dose and recommended phase 2 dose of triapine, expressed in milligrams, with an 8 weeks (56 days) timeframe. The registry record describes estimating these doses with isotonic regression based on observed dose-limiting toxicity among patients enrolled in the phase 1 portion and expansion cohort. One patient in the expansion phase was not evaluable for dose-limiting toxicity or for maximum tolerated dose determination. The record says all patients who received study drugs will be included in the safety analysis.
The registry lists overall response rate, progression-free survival, and overall survival as secondary outcomes, and reports 10 outcome measures in total. Their definitions, analysis details, and results are not reported in the registry record. The study is active, not recruiting; the listed start date is 2020-07-20 and primary completion date is 2024-09-17. Those dates describe the registry record and do not establish that all results have been posted.
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: Two participants were consented and enrolled to the study but were subsequently discovered to be screen failures. They did not receive study treatment or get assigned to an arm.
Overall Study
| Stage | Escalation Phase Dose Level 1 (100mg Triapine) | Escalation Phase Dose Level 2 (150mg Triapine) | Escalation Phase Dose Level 3 (200mg Triapine) | Expansion Phase Dose Level 1 (100mg Triapine) | Expansion Phase Dose Level 2 (150mg Triapine) |
|---|---|---|---|---|---|
| STARTED | 3 | 11 | 1 | 2 | 14 |
| COMPLETED | 3 | 11 | 1 | 2 | 14 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: One patient in the expansion phase was not evaluable for dose limiting toxicity or for MTD determination
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 | Escalation Phase Dose Level 1 (100mg Triapine) | Escalation Phase Dose Level 2 (150mg Triapine) | Escalation Phase Dose Level 3 (200mg Triapine) | Expansion Phase Dose Level 1 (100mg Triapine) | Expansion Phase Dose Level 2 (150mg Triapine) | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 11 | 1 | 2 | 14 | 31 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 10 | 0 | 1 | 11 | 24 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 1 | 1 | 3 | 7 |
| Sex: Female, Male: Female | Participants | 1 | 2 | 0 | 1 | 9 | 13 |
| Sex: Female, Male: Male | Participants | 2 | 9 | 1 | 1 | 5 | 18 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 11 | 1 | 2 | 12 | 29 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 0 | 0 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 3 | 10 | 1 | 2 | 12 | 28 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 1 | 1 |
| Region of Enrollment: United States | participants | 3 | 11 | 1 | 2 | 14 | 31 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: Grade 0 | Participants | 2 | 9 | 0 | 0 | 10 | 21 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: Grade 1 | Participants | 1 | 2 | 1 | 2 | 4 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Triapine and Recommended Phase 2 Dose (RP2D), measured over 8 weeks (56 days).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | milligrams |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns dose selection, rather than a comparison of tumor outcomes between treatment groups. Maximum tolerated dose is a dose-finding measure based on dose-limiting toxicity: it aims to identify the highest dose judged tolerable under the study's criteria. The recommended phase 2 dose is the dose selected for further study. The registry record names both measures and expresses the result in milligrams, but does not report the estimated dose or the criteria used to classify a dose-limiting toxicity.
The stated timeframe is 8 weeks (56 days). The record says isotonic regression will be used with observed dose-limiting toxicity from patients enrolled in the phase 1 portion and expansion cohort. One expansion-phase patient was not evaluable for dose-limiting toxicity or maximum tolerated dose determination. No estimate, uncertainty interval, or dose-specific toxicity result for this endpoint is reported in the registry record.
General: dose-finding endpoints address whether a regimen can be taken forward for study, not whether it improves outcomes compared with another treatment. A selected dose is an estimate based on the trial's observed safety information and design; it is not, by itself, evidence of comparative efficacy. The registry also lists overall response rate, progression-free survival, and overall survival as secondary outcomes, but does not report their results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical question is dose selection for triapine given with lutetium Lu 177 dotatate. The registry record describes an isotonic-regression approach using observed dose-limiting toxicity, but the estimated maximum tolerated dose and recommended phase 2 dose are not reported in the registry record. Consequently, the primary endpoint cannot be interpreted as a posted dose result from the information available in this record.
Enrollment is listed as 31. The record also identifies one expansion-phase patient as not evaluable for dose-limiting toxicity or maximum tolerated dose determination. That distinction matters: enrollment, evaluability for the primary dose-finding endpoint, and inclusion in a safety analysis are not necessarily interchangeable. The record states that all patients who received study drugs will be included in the safety analysis, but does not provide a complete account of the endpoint-specific analysis population.
Safety information is broken out by escalation or expansion phase and triapine dose level. The serious-event affected counts are 3 of 3 at escalation dose level 1, 8 of 11 at escalation dose level 2, 1 of 1 at escalation dose level 3, 2 of 2 at expansion dose level 1, and 11 of 14 at expansion dose level 2. These are descriptive counts within dose groups. They do not establish that one dose is safer than another: group sizes differ, dose assignment was not randomized, and the listed groups are not control arms. The record does not report whether events were judged related to study drugs.
The registry lists serious-event terms with percentages, including cardiac arrest and lymphocyte count decreased at 100.0%, anemia, neutrophil count decreased, and white blood cell decreased at 50.0%, and abdominal pain at 33.3%. The denominator and calculation basis for those percentages are not reported in the registry record. The percentages therefore should not be interpreted as overall risks or compared across groups without that context. Death counts are listed by group, but the record does not report attribution, timing, or cause for those deaths.
Overall response rate, progression-free survival, and overall survival appear among the secondary outcomes, but their estimates and analyses are not reported in the registry record. No analyses are listed. There is therefore no posted efficacy estimate or uncertainty measure to interpret from this record. The study's single-group structure also means that any outcome observed among participants would not, by itself, quantify a causal benefit relative to a control treatment.
9. Statistical Methods Explained
The registry record identifies isotonic regression as the method for estimating the maximum tolerated dose and recommended phase 2 dose from observed dose-limiting toxicity. It does not provide the dose-level toxicity data, the resulting dose estimate, or an uncertainty interval. The explanations below distinguish the stated study method from general statistical context.
What dose-finding is asking
The primary endpoint asks which triapine dose is appropriate to carry forward when combined with lutetium Lu 177 dotatate. Dose-finding studies commonly examine whether toxicity changes across dose levels, rather than compare a treatment with a control group. Here, the registry describes escalation and expansion phases and lists triapine dose levels of 100mg, 150mg, and 200mg in the safety groups. These groups are not randomized comparisons. Their observed event counts are descriptive and can be influenced by who entered each phase and dose group.
The registry defines the endpoint in terms of dose-limiting toxicity and says the estimate will use patients from the phase 1 portion and expansion cohort. However, the specific toxicity definition, observation and adjudication procedures, and decision rules are not reported in the registry record. Those details are important to interpreting what an observed toxicity count means and how it informs a dose recommendation.
What isotonic regression does
General: isotonic regression estimates a pattern under a monotonicity constraint. In dose-finding, that can represent an assumption that toxicity probability does not decrease as dose increases. The method fits an ordered pattern to observed dose-level information while respecting that constraint. It can be useful when observed rates do not rise smoothly from one dose to the next, because the fitted estimates are constrained to maintain the specified ordering.
This general description does not reveal the trial's dose recommendation. That requires the actual dose-limiting toxicity observations and the study's decision rule for choosing the maximum tolerated dose or recommended phase 2 dose. The registry record does not provide those results or the detailed algorithm beyond naming isotonic regression. The one expansion-phase patient who was not evaluable for dose-limiting toxicity or maximum tolerated dose determination further illustrates why evaluability rules matter, although the record does not explain the reason for that patient's non-evaluability.
How to read the safety counts
The posted safety groups provide the number at risk and number affected for serious events and other events, along with deaths, for each phase and dose level. These are counts within groups, not estimates adjusted for differences between groups. General: a count describes how many participants experienced an event under the registry's reporting definition; by itself, it does not indicate whether an event was caused by treatment or whether a difference between groups is statistically reliable.
The serious-event terms are also listed with percentages. A percentage is interpretable only in relation to its denominator and definition—for example, whether it refers to participants or events, and whether it is calculated within a dose group or across the study. That basis is not reported in the registry record for the listed terms. The terms and percentages should therefore be read as registry descriptions, not as complete comparative safety rates.
What uncertainty would mean
General: a confidence interval describes a range of values compatible with the observed data under the statistical model and its assumptions. Wider intervals generally indicate less precision. No confidence interval for the dose estimate, serious-event rates, or secondary outcomes is reported in the registry record. Without estimates and their uncertainty, the precision of a dose decision or outcome rate cannot be assessed from this record.
General: dose-finding conclusions can be sensitive to the number of participants observed at each dose, the definition and assessment of toxicity, and which participants contribute evaluable information. The listed group sizes vary, and one expansion participant was not evaluable for the primary endpoint. The record does not provide enough detail to evaluate the impact of those features on the dose estimate.
What is not reported
No analyses are listed in the registry record. The record does not report the dose-finding result, detailed statistical analysis plan, interim analyses, sample-size justification, confidence intervals, or results for the secondary outcomes. A planning illustration based on an observed effect, if displayed with other statistics, is not the trial's observed power or a substitute for the trial's own design rationale. General: planning calculations depend on assumptions and are not evidence about what the trial observed. The registry's record does not establish that such calculations were part of the study protocol.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures, including the primary dose-finding endpoint and the secondary outcomes overall response rate, progression-free survival, and overall survival. No analyses are listed in the registry record, and results for the secondary outcomes are not reported. The record does not describe a multiplicity strategy, such as how interpretation would account for examining multiple outcomes. It is therefore not possible to determine whether any reported statistical tests were adjusted or how confirmatory claims were prioritized.
Missing-data handling is not reported in the registry record. In particular, the record does not describe how missing outcome assessments, incomplete follow-up, or participants who discontinue treatment would be handled for the secondary outcomes. It identifies one expansion-phase patient as not evaluable for dose-limiting toxicity or maximum tolerated dose determination, but does not state why or give a broader missing-data procedure. This endpoint-specific note should not be taken as a complete account of missingness across the trial.
The primary endpoint description says that the dose estimate will be based on observed dose-limiting toxicity from patients in the phase 1 portion and expansion cohort. For safety, the record says all patients who received study drugs will be included. These statements identify relevant analysis populations in broad terms, but do not fully specify eligibility, evaluability, or handling of participants with incomplete observations. The enrollment count is 31, but that number alone does not establish the denominator for each outcome.
Because the study is single-group, there is no randomized intention-to-treat comparison to interpret. The registry record does not report an analysis plan for outcome populations or an adjustment for differences among dose groups. These omissions limit assessment of how completely the outcome reporting reflects all enrolled or treated participants.
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 |
|---|---|---|---|
| Escalation Phase Dose Level 1 (100mg Triapine) | 3 | 3 | 100.0% |
| Escalation Phase Dose Level 2 (150mg Triapine) | 8 | 11 | 72.7% |
| Escalation Phase Dose Level 3 (200mg Triapine) | 1 | 1 | 100.0% |
| Expansion Phase Dose Level 1 (100mg Triapine) | 2 | 2 | 100.0% |
| Expansion Phase Dose Level 2 (150mg Triapine) | 11 | 14 | 78.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Escalation Phase Dose Level 1 (100mg Triapine) | 0 of 3 |
| Escalation Phase Dose Level 2 (150mg Triapine) | 2 of 11 |
| Escalation Phase Dose Level 3 (200mg Triapine) | 0 of 1 |
| Expansion Phase Dose Level 1 (100mg Triapine) | 0 of 2 |
| Expansion Phase Dose Level 2 (150mg Triapine) | 2 of 14 |
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 |
|---|---|
| Escalation Phase Dose Level 1 (100mg Triapine) | 3 of 3 |
| Escalation Phase Dose Level 2 (150mg Triapine) | 11 of 11 |
| Escalation Phase Dose Level 3 (200mg Triapine) | 1 of 1 |
| Expansion Phase Dose Level 1 (100mg Triapine) | 2 of 2 |
| Expansion Phase Dose Level 2 (150mg Triapine) | 14 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Escalation Phase Dose Level 1 (100mg Triapine) | Escalation Phase Dose Level 2 (150mg Triapine) | Escalation Phase Dose Level 3 (200mg Triapine) | Expansion Phase Dose Level 1 (100mg Triapine) | Expansion Phase Dose Level 2 (150mg Triapine) |
|---|---|---|---|---|---|---|
| Lymphocyte count decreased | Investigations | 2 of 3 | 6 of 11 | 0 of 1 | 2 of 2 | 8 of 14 |
| White blood cell decreased | Investigations | 1 of 3 | 4 of 11 | 0 of 1 | 1 of 2 | 7 of 14 |
| Neutrophil count decreased | Investigations | 1 of 3 | 3 of 11 | 0 of 1 | 1 of 2 | 7 of 14 |
| Anemia | Blood and lymphatic system disorders | 1 of 3 | 2 of 11 | 0 of 1 | 1 of 2 | 4 of 14 |
| Platelet count decreased | Investigations | 1 of 3 | 3 of 11 | 0 of 1 | 0 of 2 | 4 of 14 |
| Cardiac arrest | Cardiac disorders | 0 of 3 | 0 of 11 | 1 of 1 | 0 of 2 | 0 of 14 |
| Abdominal pain | Gastrointestinal disorders | 1 of 3 | 0 of 11 | 0 of 1 | 0 of 2 | 0 of 14 |
| Hepatic hemorrhage | Hepatobiliary disorders | 1 of 3 | 0 of 11 | 0 of 1 | 0 of 2 | 0 of 14 |
| Blood bilirubin increased | Investigations | 0 of 3 | 1 of 11 | 0 of 1 | 0 of 2 | 0 of 14 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 3 | 1 of 11 | 0 of 1 | 0 of 2 | 0 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Escalation Phase Dose Level 1 (100mg Triapine) | Escalation Phase Dose Level 2 (150mg Triapine) | Escalation Phase Dose Level 3 (200mg Triapine) | Expansion Phase Dose Level 1 (100mg Triapine) | Expansion Phase Dose Level 2 (150mg Triapine) |
|---|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 3 of 3 | 10 of 11 | 0 of 1 | 2 of 2 | 12 of 14 |
| Lymphocyte count decreased | Investigations | 3 of 3 | 10 of 11 | 0 of 1 | 2 of 2 | 11 of 14 |
| White blood cell decreased | Investigations | 3 of 3 | 7 of 11 | 0 of 1 | 2 of 2 | 10 of 14 |
| Nausea | Gastrointestinal disorders | 2 of 3 | 9 of 11 | 1 of 1 | 2 of 2 | 5 of 14 |
| Platelet count decreased | Investigations | 3 of 3 | 6 of 11 | 0 of 1 | 2 of 2 | 8 of 14 |
| Fatigue | General disorders | 1 of 3 | 6 of 11 | 1 of 1 | 2 of 2 | 7 of 14 |
| Neutrophil count decreased | Investigations | 2 of 3 | 5 of 11 | 0 of 1 | 1 of 2 | 6 of 14 |
| Blood bilirubin increased | Investigations | 1 of 3 | 4 of 11 | 0 of 1 | 0 of 2 | 8 of 14 |
| Blood lactate dehydrogenase increased | Investigations | 1 of 3 | 5 of 11 | 0 of 1 | 2 of 2 | 5 of 14 |
| Alkaline phosphatase increased | Investigations | 3 of 3 | 2 of 11 | 0 of 1 | 1 of 2 | 4 of 14 |
Serious events with the highest arm-level rate: cardiac arrest (100.0%), lymphocyte count decreased (100.0%), anemia (50.0%), neutrophil count decreased (50.0%), white blood cell decreased (50.0%).
The serious-event counts are reported separately for escalation and expansion dose groups. The registry lists 3 of 3 affected at escalation phase dose level 1 (100mg Triapine), 8 of 11 at escalation phase dose level 2 (150mg Triapine), 1 of 1 at escalation phase dose level 3 (200mg Triapine), 2 of 2 at expansion phase dose level 1 (100mg Triapine), and 11 of 14 at expansion phase dose level 2 (150mg Triapine). These are counts of participants affected among those listed at risk in each group.
The groups differ in size and study phase, and there is no randomized control group. The counts are descriptive; they do not establish a causal relationship to either drug or support a like-for-like safety comparison across dose levels. The registry record does not report event attribution, timing, duration, or the specific rules used to classify seriousness.
Listed serious-event terms include cardiac arrest and lymphocyte count decreased at 100.0%; anemia, neutrophil count decreased, and white blood cell decreased at 50.0%; and abdominal pain at 33.3%. The denominator for these percentages is not reported in the registry record, so they should not be treated as whole-trial or dose-group incidence estimates. Deaths are listed as 0, 2, 0, 0, and 2 across the five groups in the order. The record does not report whether deaths were related to study treatment or their causes.
12. What the Result Does, and Does Not, Mean
The registry record describes a phase I study designed to estimate a maximum tolerated dose and recommended phase 2 dose for triapine combined with lutetium Lu 177 dotatate. It lists the planned dose-finding method and descriptive safety information, but does not report the primary dose estimate. The record therefore does not establish what dose was selected or how precisely it was estimated.
The serious-event counts provide a description of events recorded in the dose groups. They do not show that the study drugs caused those events, and they do not provide a randomized comparison of safety. The percentages attached to selected event terms lack a reported denominator definition in the registry record. Death counts are reported by group, but attribution and cause are not reported.
Overall response rate, progression-free survival, and overall survival are listed as secondary outcomes. Their results are not reported in the registry record. No analyses are listed, so this record does not provide an efficacy estimate, a comparative effect, or a measure of the precision of any efficacy result.
General: an outcome observed in a single-group study may be useful for describing participants in that study, but without a suitable comparison it cannot by itself separate treatment effects from other explanations. The escalation and expansion groups are dose and study-phase groups, not control arms. The registry record also does not report enough detail about eligibility, missing outcome data, or analysis populations to assess how representative the posted counts are of all enrolled participants.
The appropriate statistical reading is therefore narrow: the record documents the study design, an intended dose-finding approach, and safety counts by phase and dose group. It does not provide the final dose-finding result or the secondary outcome analyses needed to evaluate tumor response, progression, or survival.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary purpose is dose finding rather than a randomized comparison of clinical outcomes. In a phase I study, estimating a dose from observed toxicity is a different task from estimating whether a treatment improves an outcome relative to a control. The registry record names isotonic regression for the dose estimate, making the relationship between dose level and observed dose-limiting toxicity central to interpretation.
The escalation and expansion groups show why design context matters when reading safety counts. Group sizes vary, and phase and dose level differ. Those groups can describe the reported experience at each level, but they do not create the balance that randomization is intended to provide. Simple contrasts between their counts would not isolate a dose effect.
The record also distinguishes between participants included in the safety analysis and those evaluable for the primary dose-finding endpoint. It states that all patients who received study drugs will be included in safety analysis and identifies one expansion participant as not evaluable for dose-limiting toxicity or maximum tolerated dose determination. These different analysis purposes can produce different denominators, so enrollment alone cannot be assumed to describe every outcome population.
Finally, the registry lists response, progression-free survival, and overall survival as secondary outcomes but does not report their results. This makes it important to distinguish the trial's stated aims and outcome list from posted findings. The statistical contribution documented in this record is its dose-finding framework and descriptive safety reporting; the missing dose estimate and secondary analyses prevent assessment of the trial's eventual dose recommendation or outcome estimates.
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 dose-finding result, although it describes the method planned for estimating maximum tolerated dose and recommended phase 2 dose. Without the dose-limiting toxicity observations, decision rules, and estimate, the main endpoint cannot be evaluated. The specific definition of dose-limiting toxicity and the reason one expansion-phase patient was not evaluable are also not reported.
The trial is single-group, with no randomized comparator. Escalation and expansion dose groups differ in phase and group size, so their safety counts should not be treated as controlled comparisons. The registry does not report whether serious events or deaths were judged related to study drugs, nor does it provide the basis for the percentages attached to the listed serious-event terms.
Overall response rate, progression-free survival, and overall survival are listed, but results and analysis details are not reported in the registry record. No analyses are listed. Definitions of those outcomes, follow-up information, missing-data handling, multiplicity procedures, and confidence intervals are not reported. The record also does not state a sample-size justification, interim-analysis plan, or detailed statistical analysis plan. These omissions prevent evaluation of the precision and completeness of the study's outcome reporting.
The registry lists enrollment of 31, but does not provide a full accounting of endpoint-specific analysis populations. The stated safety population includes all patients who received study drugs, while dose-finding relies on evaluable observed toxicity. These are not necessarily identical sets of participants. As a result, the enrollment count should not be assumed to be the denominator for every reported safety or efficacy measure.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors — NCT04234568.
- Registry record last updated 2026-09-18; status last verified 2026-09.
- Results first posted 2025-11-03.
- 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
NCT04234568 is a phase I, single-group study of triapine with lutetium Lu 177 dotatate for well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. The registry lists enrollment of 31 and describes escalation and expansion phases. Treatment cycles repeat every 56 days for up to 4 cycles, subject to progression or unacceptable toxicity.
The primary endpoint is maximum tolerated dose and recommended phase 2 dose of triapine, expressed in milligrams, with an 8 weeks (56 days) timeframe. The planned method is isotonic regression using observed dose-limiting toxicity. The resulting dose estimate is not reported in the registry record. One expansion-phase patient was not evaluable for the primary dose-finding endpoint.
Safety counts are reported by phase and dose level; the record does not report event attribution or the denominator basis for selected serious-event percentages. Overall response rate, progression-free survival, and overall survival are listed as secondary outcomes, but their results are not reported in the registry record.