S1701
S1701, A Randomized Phase 2 Trial of Carboplatin-Paclitaxel With and Without Ramucirumab in Patients With Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma
Phase 2N = 21NCT03694002
- Population
- Patients with histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic thymic carcinoma, Zubrod performance status 0-2, no previous systemic therapy for advanced disease; 21 randomised, of whom 20 were eligible (one patient on the control arm did not have confirmed thymic carcinoma).
- Design
- Randomised phase 2 trial (SWOG network). Carboplatin (AUC 6) and paclitaxel (200 mg/m2) with or without ramucirumab (10 mg/kg) every 3 weeks for six cycles, followed by ramucirumab maintenance for a maximum of 1 year in the ramucirumab arm for patients with response or stable disease. Primary endpoint: progression-free survival, analysed with a one-sided 10%-level log-rank test; target sample size 66 patients (the statistical design section gives an accrual goal of 60 eligible patients). Terminated early by the Data and Safety Monitoring Board for slow accrual after 21 patients (enrolment August 2018 to October 2022).
- Primary endpoint
- PFS
- Arms
- Ramucirumab with carboplatin and paclitaxel (experimental, n = 8): Carboplatin AUC 6, paclitaxel 200 mg/m2 and ramucirumab 10 mg/kg every 3 weeks for six cycles, then ramucirumab maintenance for a maximum of 1 year
- Carboplatin and paclitaxel (control, n = 13): Carboplatin AUC 6 and paclitaxel 200 mg/m2 every 3 weeks for six cycles
- People
- Tsao AS, SWOG
PFSHR 0.51Δ median PFS+1 monthsΔ ORR+48 points
Show the numbers
| Endpoint | Analysis | Ramucirumab with carboplatin and paclitaxel | Carboplatin and paclitaxel | Effect |
|---|---|---|---|---|
| PFSRandomised patients; the paper does not name the PFS analysis population (the registry results record lists 8 and 12 eligible participants in the PFS analysis) | primaryTsao 2024 | — | — | HR 0.51P=0.13The printed interval is an 80% confidence interval, 0.24-1.09. The study was closed early and had 14 progression-free survival events at the data cutoff; the primary analysis was planned as a one-sided 10%-level log-rank test. The full text states that PFS 'was improved with RCP, though the difference was not statistically significant', so the hazard ratio of 0.51 is for the ramucirumab arm relative to control. The authors write that the lack of statistical significance was likely due to small sample sizes. |
| PFSRandomised patients; the paper does not name the analysis population (the registry results record lists 8 and 12 eligible participants) | primarymedian follow-up 16.7 monthsTsao 2024 | median 8 months | median 7 months | Medians as printed in the full text (rounded to whole months); the printed 80% confidence intervals are 7-11 months for the ramucirumab arm and 6-8 months for the control arm, and the median follow-up of 16.7 months is among patients still alive. Overall survival was immature: a single death had been reported. |
| ORRPatients with measurable disease: 8 on the ramucirumab arm and 10 on the control arm | primaryTsao 2024 | 88% | 40% | P=0.04Seven of eight patients responded on the ramucirumab arm (80% CI 59-99) and four of ten on the control arm (80% CI 19-65); the intervals are 80% confidence intervals. All responses were partial. Disease control rate 100% versus 70% (p = 0.09). Safety (abstract): no grade 4 or worse treatment-related adverse events on the ramucirumab arm, where 50% had grade 3 events including one grade 3 thromboembolic event; among nine patients assessable for toxicity on the control arm, one (11%) had grade 4 neutropenia and one (11%) a grade 3 thromboembolic event. |
| Endpoint | Analysis | Ramucirumab with carboplatin and paclitaxel | Carboplatin and paclitaxel | Effect |
|---|---|---|---|---|
| PFSRandomised patients; the paper does not name the PFS analysis population (the registry results record lists 8 and 12 eligible participants in the PFS analysis) | primaryTsao 2024 | — | — | HR 0.51P=0.13The printed interval is an 80% confidence interval, 0.24-1.09. The study was closed early and had 14 progression-free survival events at the data cutoff; the primary analysis was planned as a one-sided 10%-level log-rank test. The full text states that PFS 'was improved with RCP, though the difference was not statistically significant', so the hazard ratio of 0.51 is for the ramucirumab arm relative to control. The authors write that the lack of statistical significance was likely due to small sample sizes. |
| PFSRandomised patients; the paper does not name the analysis population (the registry results record lists 8 and 12 eligible participants) | primarymedian follow-up 16.7 monthsTsao 2024 | median 8 months | median 7 months | Medians as printed in the full text (rounded to whole months); the printed 80% confidence intervals are 7-11 months for the ramucirumab arm and 6-8 months for the control arm, and the median follow-up of 16.7 months is among patients still alive. Overall survival was immature: a single death had been reported. |
| ORRPatients with measurable disease: 8 on the ramucirumab arm and 10 on the control arm | primaryTsao 2024 | 88% | 40% | P=0.04Seven of eight patients responded on the ramucirumab arm (80% CI 59-99) and four of ten on the control arm (80% CI 19-65); the intervals are 80% confidence intervals. All responses were partial. Disease control rate 100% versus 70% (p = 0.09). Safety (abstract): no grade 4 or worse treatment-related adverse events on the ramucirumab arm, where 50% had grade 3 events including one grade 3 thromboembolic event; among nine patients assessable for toxicity on the control arm, one (11%) had grade 4 neutropenia and one (11%) a grade 3 thromboembolic event. |
- Ramucirumab with carboplatin and paclitaxel (experimental)
- Carboplatin and paclitaxel (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Ramucirumab with carboplatin and paclitaxel | Carboplatin and paclitaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 64.8% | 61.0% |
| 10 | 42.0% | 37.1% |
| 15 | 27.3% | 22.6% |
| 20 | 17.7% | 13.8% |