Table 2.
Examples of master protocol trials in oncology.
| Trial name | Design | Targeted drug | Main diseases | target | Number of patients | Endpoint | Woodcock & LaVange [22] | Cunanan et al. [21] | Renfro & Sargent [23] | Renfro & Mandrekar [13] |
|---|---|---|---|---|---|---|---|---|---|---|
| B2225 | Ph2 (phase 2), multi-center, unblinded, uncontrolled | Imatinib | 40 carcinomas (solid, hematologic) | – | 186 | Response rate | basket | – | – | – |
| BRAF V600 | Ph2, multi-center, unblinded, uncontrolled | Vemurafenib, cetuximab | Multiple carcinomas | BRAF V600 | 122 | Response rate | basket | basket | – | – |
| AcSe | Ph2, multi-center, unblinded, uncontrolled | Crizotinib | Gastrointestinal, breast, cancer, ovarian, thyroid cancers, sarcoma, etc. | ALK, MET, RON, ROS1 | 488 | Response rate | – | – | basket | – |
| NCI-Match | Ph2, multi-center, uncontrolled | 30 approved and unapproved treatments targeting genetic mutations | Advanced solid tumors, lymphomas, myelomas (mutation measured) | EGFR, MET, ALK, ROS1, BRAF V600, mTOR, etc. | 35/sub-study | Response rate, PFS rate | umbrella | – | basket | basket |
| ALCHEMIST | Ph3, multi-center, unblinded, randomized | Erlotinib, crizotinib, nivolumab | Pulmonary adenocarcinoma | EGFR, ALK, PD-L1 | ≥770 | OS, DFS | – | – | umbrella | umbrella |
| LUNG-MAP | Seamless Ph2/3, randomized | Erlotinib, ipilimumab, nivolumab, palbociclib, etc. | Squamous cell non-small cell lung carcinoma (NSCLC) | PIK3CA, FGFR, CCDN1, D2, CDK4, c-MET | 100-170 (Ph2) 300-400 (Ph3) |
Response rate, PFS, OS | master protocol | – | umbrella | |
| FOCUS4 | Ph2/3, multi-center, unblinded, randomized | Molecular target drugs such as BRAF inhibitors, etc. | Colorectal cancer | BRAF, PIK3CA, PTEN, KRAS, NRAS | Approx.2000 | PFS, OS | – | – | umbrella | platform |
| BATTLE-1 | Ph2, single-center, adaptive-randomized | Erlotinib, vandetanib, sorafenib, erlotinib + bexarotene | Advanced NSCLC | EGFR, KRAS, BRAF, VEGF, RXRs/CyclinD1 | 255 | Response rate, PFS, OS, toxicity | umbrella | – | platform | – |
| I-SPY 2 | Ph2, multi-center, adaptive-randomized | Pembrolizumab, trastuzumab, pertuzumab, neratinib, etc. | Early high-risk breast cancer | HR, HER2, MammaPrint | 1920 | Pathological response rate | platform | – | platform | – |
| SHIVA | Ph2, multi-center, unblinded, randomized | Erlotinib, lapatinib + trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen | Advanced tumors resistant to standard treatment | Hormone receptor, PI3KA, KT, mTOR, RAF, MEK | 195 | PFS | – | – | platform, etc. | – |
| NCI-MPACT | Ph2, multi-center, unblinded, randomized | PARP inhibitors, Wee 1 inhibitors, everolimus, trametinib | Advanced solid tumors | DNA repair, PI3K, RAS/RAF/MEK | 180 | Response rate, PFS rate | – | – | platform, etc. | – |
| CUSTOM | Multi-center, unblinded, uncontrolled | Erlotinib, selumetinib, AKT inhibitors, lapatinib, sunitinib | NSCLC, small cell lung carcinoma, thymic carcinoma | EGFR, KRAS, HRAS, NRAS, BRAF, PTEN, Akt 1, PIK3CA, ERBB2, KIT, PDGFRA | 647 | Response rate | – | basket | platform, etc. | – |
| CREATE | Ph2, multi-center, unblinded, uncontrolled | Crizotinib | Advanced cancers such as sarcomas | ALK, MET | 582 | Tumor regression | – | basket | platform, etc. | – |
OS: Overall survival, PFS: Progression-free survival, DFS: Disease-free survival.