Table 2.
Ongoing clinical trials using targeted therapies in hepatoblastoma
| ClinicalTrials.gov identifier | Drug name | HB participants (enrollment) | Phase | Study status | Targets | Relative signaling pathway(s) |
|---|---|---|---|---|---|---|
| NCT01125800 | Sonidegib | 1 (76) | Ph I/II | Completed | Smoothened | Hedgehog pathway119 |
| NCT02867592 | Cabozantinib S-malate | ? (146) | Ph II | Recruiting | RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, and TIE-2 | VEGFR2, c-MET pathways, etc.120,121 |
| NCT04195555 | Ivosidenib | ? (49) | Ph II | Not yet recruiting | IDH1 | IDH pathway122 |
| NCT04308330 | Vorinostat | ? (30) | Ph I | Recruiting | HDAC | VEGF, ATM, androgen, and estrogen pathways123–125 |
| NCT04320888 | Selpercatinib | ? (49) | Ph II | Not yet recruiting | RET kinase | RET pathway126 |
| NCT03213652 | Ensartinib | ? (98) | Ph II | Recruiting | ALK | EGFR, KRAS, PIK3CA, ERBB2 pathways127 |
| NCT04284774 | Tipifarnib | ? (49) | Ph II | Not yet recruiting | Farnesyltransferase | RAS and PI3K/Akt pathways128 |
| NCT03526250 | Palbociclib | ? (49) | Ph II | Recruiting | CDK4/6 | CDK-RB-E2F pathway129 |
| NCT03698994 | Ulixertinib | ? (49) | Ph II | Recruiting | ERK2 | MAPK/ERK pathway130 |
| NCT03213704 | Larotrectinib | ? (49) | Ph II | Recruiting | TrkA, TrkB, TrkC | TRK pathway131 |
| NCT03233204 | Olaparib | ? (49) | Ph II | Recruiting | PARP-1/2 | HR, BER/SSBR pathways132 |
| NCT01154816 | Alisertib | 6 (118) | Ph II | Completed | AAK | PI3K/Akt/mTOR pathway133 |
| NCT03220035 | Vemurafenib | ? (49) | Ph II | Recruiting | B-Raf | MAPK/ERK pathway134 |
| NCT01331135 | Sirolimus | ? (24) | Ph I | Active, not recruiting | mTOR | mTOR pathway135 |
| NCT03213678 | Samotolisib | ? (144) | Ph II | Recruiting | PI3K/mTOR | PI3K/Akt/mTOR pathway136 |
| NCT03213665 | Tazemetostat | ? (49) | Ph II | Recruiting | EZH2 | EZH2 histone methyltransferase137 |
| NCT03210714 | Erdafitinib | ? (49) | Ph II | Recruiting | pan-FGFR | FGFR1–4 pathway138 |
| NCT02390843 | Simvastatin | ? (13) | Ph I | Completed | HMG-CoA reductase | IL6/STAT3 pathway139,140 |
| NCT00831844 | Cixutumumab | 10 (116) | Ph II | Completed | IGF1R | IGF and PI3K/Akt/mTOR pathways141 |
| NCT02085148 | Regorafenib | ? (60) | Ph I | Active, not recruiting | VEGFR1-3, c-KIT, TIE-2, PDGFR-β, FGFR-1, RET, RAF-1, BRAF, p38 MAP kinase | VEGF, RAF/MEK/ERK pathways, etc.142,143 |
| NCT03155620 | Samotolisib, | ? (1,500) | Ph II | Recruiting | PI3K/mTOR | PI3K/AKT/mTOR pathway136 |
| Selpercatinib, Selumetinib sulfate, | RET kinase MEK | RET pathway126 MAPK/ERK pathway144 | ||||
| Tazemetostat, | EZH2 | EZH2 histone methyltransferase137 | ||||
| Tipifarnib, | Farnesyltransferase | Ras and PI3K pathways128 | ||||
| Ulixertinib, | ERK2 | MAPK/ERK pathway130 | ||||
| Vemurafenib | B-Raf | MAPK/ERK pathway134 |
Abbreviations: AAK, Aurora A kinase; ALK, anaplastic lymphoma kinase; BER/SSBR, base excision repair/single strand break repair; CDKs, cyclin-dependent kinases; EGFR, endothelial growth factor receptor; ERK, extracellular signal-related kinases; EZH2, enhancer of zeste homolog 2; FGFR, fibroblast growth factor receptor; FLT-3,: FMS-like receptor tyrosine kinase-3; HDAC, histone deacetylases; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; HR, homologous recombination; IDH1, isocitrate dehydrogenase-1; IGF1R, insulin-like growth factor 1 receptor; IL-6, interleukin-6; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PARP, poly (ADP-ribose) polymerase; PDGFR-β, platelet-derived growth factor receptor β; PI3K, phosphatidylinositol 3-kinase; STAT, signal transducer and activator of transcription; TRK, tropomyosin receptor kinase; TRKB, tropomyosin receptor kinase B; VEGFR, vascular endothelial growth factor receptor.