Table 1 Summary of the included studies for Phase II two-stage clinical trials in glioblastoma
From: Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review
First Author (Year) | General study design | Key information for Two-stage design implementation | |||||
|---|---|---|---|---|---|---|---|
Tumor type | Setting | Agent | Patient | PE | Design type | Type I Error | |
Chamberlain et al. (2011) [18] | GBM | Recurrent | BEN | Adult | PFS6 | Simon (Minimax) | 5% |
Ananda et al. (2011) | GBM | Recurrent | TMZ + PLD | Adult | PFS6 | Simon (Optimal) | 10% |
Neyns et al. (2011) [19] | Hight-grade glioma | Recurrent | SNT | Adult | Other | Simon (Minimax) | 10% |
Warren et al. (2012) [20] | Hight-grade glioma | Recurrent | TMZ + O6B | Pediatric | ORR | Gehan | NI |
Geoerger et al. (2012) [21] | Hight-grade glioma | Recurrent | TMS | Pediatric | ORR | Simon (Optimal) | 10% |
Pan et al. (2012) [22] | GBM | Recurrent | SNT | Adult | PFS6 | Simon (Minimax) | 10% |
Santoni et al. (2012) [23] | GBM | Recurrent | TMZ | Adult | PFS6 | Simon’s Two-stage | 10% |
Hu et al. (2013) [24] | GBM | Recurrent | GMT | Adult | PFS6 | Simon (Optimal) | 5% |
Lassen et al. (2013) [25] | GBM | Recurrent | BEV + TEM | Adult | Other | Simon’s two-stage | NI |
Hargrave et al. (2013) [26] | Hight-grade glioma | Newly diagnosed | TMZ + IRI | Pediatric | ORR | Simon (Optimal) | 5% |
Tawbi et al. (2013) [27] | Brain metastasis | Newly diagnosed | TMZ + DAC | Adult | ORR | Admissible | 10% |
Muhic et al. (2013) [28] | GBM | Recurrent | NIN | Adult | ORR | Two-stage | 5% |
Burzynski et al. (2014) [29] | Hight-grade glioma | Recurrent | A10 + AS2-1 | Pediatric | ORR | Two-stage | NI |
Norden et al. (2015) [30] | Hight-grade glioma | Recurrent | NIN | Adult | PFS6 | Simon (Optimal) | (A) 7.5% (B) 7.5% |
Taylor et al. (2015) [31] | GBM | Recurrent | BOS | Adult | PFS6 | Simon (Optimal) | 5% |
Lassman et al. (2015) [32] | GBM | Recurrent | DAS | Adult | PFS6 ORR | Simon’s two-stage | NI |
Kalpathy-Cramer et al. (2017) [33] | GBM | Recurrent | TIV | Adult | PFS6 | Simon’s Two-stage | NI |
Arrillaga-Romany (2017) [34] | GBM | Recurrent | IMI | Adult | PFS6 | Simon’s Two-stage | 5% |
Pellegatta et al. (2018) [35] | GBM | Newly diagnosed | TMZ + DEN | Adult | PFS12 | Simon’s Two-stage | NI |
Lee et al. (2019) [36] | GBM | Recurrent | BEV + PON | Adult | PFS3 | Simon (Optimal) | 10% |
Silvani et al. (2019) [37] | GBM | Recurrent | ORT | Adult | PFS6 | Simon (Optimal) | 10% |
Du et al. (2019) [38] | GBM | Newly diagnosed | TMZ + NIN | Adult | PFS6/OS12 | Simon (Optimal) | 5% |
Sharma et al. (2019) [39] | GBM | Recurrent | DOV | Adult | PFS6 | Simon’s Two-stage | 10% |
Kaley et al. (2019) [40] | GBM | Recurrent | PRF | Adult | PFS6 | Simon (Optimal) | 10% |
Le Rhun et al. (2019) [41] | GBM | Newly diagnosed | THR | Adult | Other | Fleming | 5% |
Brenner et al. (2021) [42] | GBM | Recurrent | EVO + BEV | Adult | PFS4 | Simon (Optimal) | 5% |
Altwairgi et al. (2021) [43] | GBM | Newly diagnosed | TMZ + ATO | Adult | PFS6 | Two-stage | 5% |
Pasquualini et al. (2021) [44] | Hight-grade glioma | Recurrent | NIV + CYC | Pediatric | ORR | Simon (Minimax) | 10% |
Fangusaro et al. (2021) [45] | Hight-grade glioma | Recurrent | POM | Pediatric | ORR | Simon (Optimal) | 5% |
Key information for Two-stage design implementation | Results from sample size calculation | Study results | ||||||
|---|---|---|---|---|---|---|---|---|
Type II error | response rate (p0) | response rate (p1) | Total (N) | Stage 1 (N1) | Stage 1 Rejection No. (R1) | Total Rejection No (R) | Stopped after stage 1? | Further investigation needed |
19% | 15% | 25% | 31 | 16 | 1 | NI | Stopped | Ineffective |
10% | 40–50% | 50–70% | 40 | 21 | NI | NI | Completed | Ineffective |
10% | 5% | NI | 32 | 18 | 0 | 3 | Stopped | Ineffective |
NI | 5% | 17% | 25 | 16 | 1 | NI | Stopped | Ineffective |
10% | 8% | 30% | 25 | 12 | 1 | 3 | Stopped | Ineffective |
20% | 10% | 25% | 31 | 16 | 1 | 5 | Stopped | Ineffective |
10% | 10% | 25% | NI | NI | NI | NI | Stopped | Ineffective |
20% | 15% | 30% | 55 | 19 | 3 | NI | Stopped | Ineffective |
20% | NI | NI | 32 | 13 | NI | NI | Stopped | Ineffective |
20% | 5% | 20% | 29 | 10 | 0 | 3 | Stopped | Ineffective |
15% | 7% | 21% | 34 | 14 | 0 | 4 | Completed | Effective |
24% | 10% | 25% | 32 | 16 | 3 | NI | Stopped | Ineffective |
NI | NI | 10% | 40 | 20 | 0 | NI | Stopped | Ineffective |
(A) 20% (B) 20% | (A) 36% (B) 20% | (A) 55% 40% | NI | 14 | NI | NI | Stopped | Ineffective |
20% | 9% | 30% | 30 | 10 | 1 | 5 | Stopped | Ineffective |
5% | 11% | 25% | 77 | 27 | 2 | NI | Stopped | Ineffective |
20% | NI | NI | 18 | 5 | 0 | NI | Stopped | Ineffective |
16% | 10% | 30% | 30 | 17 | NI | NI | Stopped | Ineffective |
NI | 27% | 42% | 74 | 24 | 7 | NI | Stopped | Ineffective |
20% | 15% | 35% | 27 | 15 | 4 | 9 | Stopped | Ineffective |
10% | 20% | 35% | 58 | 33 | 6 | NI | Stopped | Ineffective |
10% | 66% | 87% | 35 | NI | NI | NI | Completed | Effective |
20% | 36% | 55% | 32 | 19 | 7 | 14 | Stopped | Ineffective |
10% | 5% | 20% | 37 | 12 | 0 | 3 | Stopped | Ineffective |
5% | 10% | 35% | 31 | 20 | 2 | 6 | Stopped | Ineffective |
20% | 10.9% | 28.9% | 33 | 11 | 1 | 6 | Completed | Effective |
20% | 55% | 75% | 32 | 15 | NI | NI | Completed | Ineffective |
10% | 10% | 30% | 25 | 12 | 1 | 5 | Stopped | Ineffective |
10% | 10% | 40% | 20 | 9 | 1 | 4 | Completed | Ineffective |