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-1 |
|---|---|
| Design | Single-group |
| Masking | None |
| Primary purpose | Treatment |
| Intervention | Entrectinib |
| Lead sponsor | Hoffmann-La Roche |
| Status | Completed |
2. Clinical Question
Population
Adults with locally advanced or metastatic solid tumors.
Intervention
Oral entrectinib.
Comparator
No comparator; the study used a single-group design.
Primary question
What dose-related safety and activity measures are observed with entrectinib?
3. Trial Design
84 patients
Entrectinib
Safety and response
4. Endpoints
| Endpoint | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity (DLT) | 28 days following first dose of entrectinib | Determine dose-limiting toxicities of entrectinib. |
| Maximum Tolerated Dose (MTD) | 28 days following first dose of entrectinib | Determine MTD of entrectinib. |
| Recommended Phase 2 Dose (RP2D) | Approx. 6 months | Determine RP2D of entrectinib. |
| Overall Response Rate (ORR) in Dose Expansion | Approx. 2 months | Per RECIST v1.1 as assessed by Investigator. |
5. Planned Analysis
The registry reports the planned measurement of dose-limiting toxicity, maximum tolerated dose, recommended phase 2 dose, and overall response rate in dose expansion. No statistical analyses or results are posted on ClinicalTrials.gov.
For a phase 1 dose-finding study, safety endpoints such as DLTs and MTD are typically evaluated using observed toxicity patterns during the dose-evaluation period. Dose escalation decisions are generally based on prespecified rules. Response endpoints such as ORR are commonly summarized using response proportions with confidence intervals when sufficient evaluable patients are available.
6. Statistical Methodology
Dose-finding analysis
Early-phase oncology studies commonly focus on identifying a tolerable dose rather than formally comparing randomized treatment groups. The statistical emphasis is therefore on safety characterization, dose selection, and estimation of clinically relevant activity signals.
Response rate estimation
Overall response rate is a binary endpoint representing the proportion of assessed patients meeting response criteria. A confidence interval provides information about uncertainty around that estimated proportion.
7. Statistical Methods Explained
Why was a single-group design used?
A single-group phase 1 design is commonly used when the primary goal is dose evaluation and early safety characterization rather than comparative efficacy.
What does maximum tolerated dose mean?
MTD describes the highest dose considered tolerable according to the study's dose-evaluation framework.
Why is recommended phase 2 dose important?
The RP2D provides the dose selected for later development based on the balance between tolerability and observed activity.
How is overall response rate interpreted?
ORR describes tumor responses observed under the response assessment criteria. It does not by itself measure survival duration or comparative treatment benefit.
Why are confidence intervals useful?
Confidence intervals describe uncertainty around estimates and help distinguish precise estimates from those based on limited information.
8. Limitations
- The single-group design does not provide a randomized comparator.
- Phase 1 studies are primarily designed for dose and safety assessment.
- The registry does not report posted statistical analyses or efficacy estimates.
- Response rates from dose expansion require interpretation within the enrolled molecularly selected population.
9. Why This Trial Matters Statistically
| Concept | How it appears in STARTRK-1 |
|---|---|
| Early-phase design | Focus on safety, tolerability, and dose selection |
| DLT evaluation | Assessment during the first 28 days following first dose |
| Dose selection | Determination of MTD and RP2D |
| Response assessment | ORR evaluated per RECIST v1.1 |