This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
| Feature | STARTRK-NG |
|---|---|
| Intervention | Entrectinib |
| Design | Non-randomized, single-group |
| Masking | None |
| Primary purpose | Treatment |
| Status | Active, not recruiting |
| Sponsor | Hoffmann-La Roche |
| Start date | 2016-05-03 |
| Primary completion date | 2026-06-30 |
2. Clinical Question
Population
Children and adolescents with locally advanced or metastatic solid tumors and/or primary CNS tumors and no satisfactory treatment options.
Intervention
Entrectinib.
Comparator
No comparator arm. The study uses a single-group design.
Primary question
What dose levels and recommended phase 2 doses can be identified, and what objective response rates are observed in specified cohorts?
3. Trial Design
STARTRK-NG is a phase 1/2, non-randomized, open-label, single-group treatment study. The registry reports 69 participants and seven arms evaluating different pediatric formulations and dosing approaches of entrectinib.
| Design element | Description |
|---|---|
| Allocation | Non-randomized |
| Model | Single group |
| Masking | None |
| Arms | 7 |
4. Endpoints
| Endpoint | Time frame | Assessment |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Approximately 6 months | NCI CTCAE v4.03 |
| RP2D of F1 formulation in pediatric participants able to swallow intact capsules | Approximately 6 months | NCI CTCAE v4.03 |
| RP2D of F06 formulation in pediatric participants able to swallow intact capsules | Approximately 6 months | NCI CTCAE v4.03 |
| RP2D of F06 formulation in pediatric participants dosed via feeding tube | Approximately 6 months | NCI CTCAE v4.03 |
| RP2D of Minitablets/F15 formulation | Approximately 6 months | NCI CTCAE v4.03 |
| Cohort B Objective Response Rate | Approximately 6 months | RANO per BICR |
| Cohort D Objective Response Rate | Approximately 6 months | RECIST v1.1 per BICR |
5. Planned Analysis
The ClinicalTrials.gov record lists primary endpoints but does not report posted statistical analyses or outcome results.
For dose-finding endpoints such as Maximum Tolerated Dose and Recommended Phase 2 Dose, analysis generally focuses on observed adverse events, dose-limiting toxicities, and tolerability patterns assessed using predefined toxicity criteria.
For objective response rate, analysis typically summarizes the proportion of participants achieving a complete or partial response according to the specified response assessment framework. Confidence intervals may be used to describe precision around the estimated response proportion.
6. Statistical Methodology
Dose escalation and tolerability assessment
Phase 1 oncology studies commonly use structured dose evaluation approaches to identify doses that provide acceptable tolerability. The key statistical challenge is balancing limited participant numbers with the need to characterize toxicity across dose levels.
Objective response rate analysis
Objective response rate is a binary endpoint: each participant is classified according to whether a prespecified response criterion is achieved. Unlike time-to-event endpoints, ORR does not directly describe duration of benefit.
A response proportion answers the question of how many evaluated participants met the response definition. It does not by itself measure survival, durability, comparative benefit, or superiority versus another treatment because STARTRK-NG does not include a randomized comparator.
7. Statistical Methods Explained
Why is this trial not analyzed like a randomized phase 3 trial?
The study uses a single-group design, so treatment comparisons between randomized groups are not available. Interpretation focuses on dose selection, safety, and observed activity within defined cohorts.
What does Maximum Tolerated Dose measure?
MTD summarizes the highest evaluated dose considered tolerable under the study's toxicity assessment framework. It is a dose-selection endpoint rather than an efficacy endpoint.
Why is Objective Response Rate different from survival?
ORR measures tumor response status at assessment points, whereas survival endpoints measure time until an event such as death. They describe different aspects of treatment effect.
Why are confidence intervals important for response rates?
A confidence interval describes uncertainty around an estimated response proportion. Small studies can produce imprecise estimates even when the observed response proportion appears notable.
8. Limitations
- No randomized comparator: Treatment effects cannot be compared directly with another treatment group within the study.
- Single-group design: Observed outcomes may reflect patient selection and disease characteristics as well as treatment exposure.
- Small enrollment: The registry reports enrollment of 69 participants, limiting precision for many estimates.
- Endpoint diversity: Dose, formulation, safety, and response endpoints address different statistical questions.
- No posted statistical analyses: The registry does not report formal statistical analysis results for this study.
9. Why This Trial Matters Statistically
STARTRK-NG illustrates several important concepts in early-phase clinical trial statistics.
| Concept | Application |
|---|---|
| Early-phase design | Dose selection and tolerability assessment |
| Single-group analysis | Interpretation without randomized comparison |
| Safety endpoints | Use of standardized toxicity criteria |
| Response endpoints | Assessment using RANO and RECIST frameworks |