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
SHIVA was a randomized phase II treatment trial evaluating whether therapy selected according to tumor molecular profiling improved progression-free survival compared with conventional chemotherapy in patients with recurrent or metastatic solid tumor disease.
| Feature | SHIVA |
|---|---|
| Title | A Randomized Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer |
| Population | Patients with recurrent/metastatic solid tumor disease |
| Allocation | Randomized |
| Masking | None |
| Primary purpose | Treatment |
| Sponsor | Institut Curie |
2. Clinical Question
Population
Patients with recurrent or metastatic solid tumor disease.
Intervention
Targeted therapy based on molecular profiling, including therapies selected according to tumor biopsy findings.
Comparator
Conventional chemotherapy.
Primary question
Does molecular profiling-based targeted therapy improve progression-free survival compared with conventional therapy?
3. Trial Design
Patients were assigned in a randomized phase II design.
The registry identifies the design model as crossover.
Tumor evaluation was performed according to RECIST 1.1 criteria every 2 months.
The study included two treatment arms.
4. Endpoints
| Endpoint | Definition |
|---|---|
| Patient's progression free survival | Progression free survival according to RECIST 1.1 of targeted therapy based on molecular profiling versus conventional chemotherapy. |
| Tumor evaluation | Tumor evaluation according to RECIST 1.1 criteria every 2 months. |
5. Planned Analysis
The registry identifies progression-free survival according to RECIST 1.1 as the primary endpoint. Progression-free survival is generally analyzed as a time-to-event outcome, using methods such as Kaplan-Meier estimation to describe event timing and comparative methods such as log-rank testing or Cox regression when prespecified.
6. Statistical Methodology
Progression-free survival
Progression-free survival measures the time from a defined starting point until disease progression or death. Because not every patient experiences an event during follow-up, censoring methods are used to incorporate available follow-up information.
RECIST 1.1 assessment
The primary endpoint was based on tumor evaluation using RECIST 1.1 criteria. Imaging-based response criteria provide a standardized framework for determining disease progression.
Crossover design considerations
Crossover designs allow treatment pathways to change after predefined circumstances. Statistical interpretation must account for the timing and consequences of treatment switching when comparing randomized groups.
7. Statistical Methods Explained
Why is progression-free survival a time-to-event endpoint?
Patients experience progression at different times. A time-to-event framework uses the timing of events rather than only whether an event occurred.
Why use Kaplan-Meier estimation?
Kaplan-Meier methods estimate event-free probability over time while accounting for patients whose outcomes are not yet observed.
Why does censoring matter?
Censored observations still contribute information until the last time they were known to be event-free.
Why does crossover affect interpretation?
If patients receive another treatment after assignment, the comparison may reflect both the initial assignment and later treatment pathways.
8. Limitations
- The registry does not report posted statistical analyses or numerical outcome estimates.
- The primary endpoint depends on RECIST 1.1-based progression assessment, which requires consistent evaluation procedures.
- The crossover design requires careful interpretation of treatment comparisons.
- ClinicalTrials.gov does not report subgroup analyses, safety comparisons, or additional efficacy estimates.
9. Why This Trial Matters Statistically
| Concept | How it appears in SHIVA |
|---|---|
| Randomization | Randomized phase II comparison of two treatment strategies. |
| Personalized treatment | Therapy selection based on tumor molecular profiling. |
| Time-to-event analysis | Primary endpoint based on progression-free survival. |
| RECIST assessment | Tumor evaluation framework for progression assessment. |
| Crossover | Design model identified by the registry. |
10. Related Tutorials
Learn more about the methods used in this trial: