Table 4.
Clinical Trials for BTC Targeted Therapy Targeting the Ras/Raf/MEK/Erk Signaling Pathway
| Target | Drugs | ClinicalTrials.gov Identifier | Status | Phase | Disease | Number of Patients | Design |
|---|---|---|---|---|---|---|---|
| BRAF | Vemurafenib | NCT01524978 | Completed | II | CCA with BRAF V600 mutation Other solid tumors with BRAF V600 mutation |
208 | Vemurafenib |
| PLX8394 | NCT02012231 | Terminated | I II |
CCA, Other malignancies | 5 | PLX8394 | |
| NCT02428712 | Active, not recruiting | I II |
Advanced solid tumors with BRAF mutations | 75 | PLX8394 | ||
| Dabrafenib | NCT02465060 | Recruiting | II | Malignancies with BRAF V600E/R/K/D mutation | 6452 | Dabrafenib plus Trametinib | |
| NCT02034110 | Active, not recruiting | II | Rare cancers (including BTCs) with BRAF V600E mutations. | 206 | Dabrafenib plus Trametinib | ||
| Regorafenib | NCT02162914 | Active, not recruiting | II | CCA | 66 | Regorafenib vs Placebo | |
| NCT02053376 | Completed | II | CCA | 43 | Regorafenib | ||
| NCT02115542 | Active, not recruiting | II | CCA | 39 | Regorafenib | ||
| NCT03475953 | Recruiting | II | BTC, Other solid tumor types | 362 | Regorafenib plus Avelumab | ||
| Sorafenib | NCT00661830 | Completed | II | BTC | 103 | Sorafenib plus Gemcitabine vs Gemcitabine plus Placebo | |
| NCT00919061 | Completed | II | BTC | 39 | Sorafenib plus GEMCIS | ||
| NCT00634751 | Completed | I II |
BTC, Pancreatic Neoplasms | 48 | Sorafenib plus Oxaliplatin plus Capecitabine | ||
| NCT00238212 | Completed | II | BTC | 50 | Sorafenib | ||
| NCT01093222 | Completed | II | BTC | 40 | Sorafenib and Erlotinib | ||
| NCT03768375 | Recruiting | II | BTC | 150 | Sorafenib plus GEMOX vs GEMOX | ||
| NCT02836847 | Recruiting | II | BTC | 152 | Sorafenib plus GEMOX vs GEMOX | ||
| MEK | Selumetinib | NCT00553332 | Completed | II | BTC | 29 | Selumetinib |
| NCT01242605 | Completed | I | BTC | 13 | Selumetinib plus GEMCIS | ||
| NCT02151084 | Active, not recruiting | II | BTC | 57 | Selumetinib plus GEMCIS vs GEMCIS | ||
| NCT02586987 | Completed | I | BTC, Other solid tumor types | 58 | Selumetinib plus MEDI4736 vs Selumetinib plus MEDI4736 plus Tremelimumab | ||
| Refametinib | NCT02346032 | Completed | II | BTC | 4 | Refametinib | |
| Trametinib (GSK1120212) | NCT01438554 | Completed | I | CCA, Thyroid cancer, Soft-tissue sarcoma | 89 | Trametinib plus Pazopanib | |
| NCT02042443 | Completed | II | BTC | 53 | Trametinib vs Chemotherapy (Leucovorin calcium plus Fluorouracil or Capecitabine) | ||
| NCT02465060 | Recruiting | II | Malignancies with BRAF V600E/R/K/D mutation | 6452 | Trametinib plus Dabrafenib | ||
| NCT01943864 | Completed | II | BTC | 20 | Trametinib | ||
| NCT01324258 | Completed | II | BTC, Other solid tumor types | 19 | Trametinib vs Trametinib plus Gemcitabine | ||
| MEK162 (binimetinib) | NCT02773459 | Completed | I II |
BTC | 31 | MEK162 plus Capecitabine | |
| NCT00959127 | Completed | I | BTC, Colorectal cancer | 93 | MEK 162 | ||
| NCT01828034 | Completed | I | BTC | 42 | MEK162 plus GEMCIS | ||
| NCT02465060 | Recruiting | II | Malignancies with NRAS mutation in codon 12, 13, or 61 | 6452 | MEK 162 | ||
| RAS | Tipifarnib (R115777) | NCT00005842 | Completed | I | Advanced Cancer | 24 | Tipifarnib plus Trastuzumab |
| ERK | JSI-1187 | NCT04418167 | Recruiting | I | Advanced solid tumors with MAPK pathway mutations | 124 | JSI-1187 vs JSI-1187 plus Dabrafenib |