Table 2.
Completed or ongoing clinical trials for neurofibromatosis type 1-associated plexiform neurofibroma
| Drug | Phase | Target | Age (y) | Endpoint | Results |
|---|---|---|---|---|---|
| Sorafenib156 | 1 | Raf, PDGFRβ, c-kit,VEGFR2 | 3–18 | Toxicity, PK, 3D ORR | Intolerable – pain |
| Tipifarnib67 | 1,2 | Farnesyl Transferase | 3–25 | WHO; TTP 3D ORR | Inactive |
| Pirfenidone157,158 | 1,2 | Fibroblast | 3–21 | 3D ORR | Inactive/unclear |
| Thalidomide159 | 1 | Angiogenesis | >5 | WHO ORR | Inactive/unclear |
| Ketotifen fumarate160 | 2 | Anti-histamine | 6–55 | Symptom improvement | Inactive/unclear |
| PEG-Interferon alpha 2b61 | 1, 2 | Immune; Angiogenesis | 1–34 | TTP, 3D ORR | 29% 3D ORR |
| Sirolimus68 | 2 | mTOR | >3 | TTP, 3D ORR | TTP – active No RR |
| Imatinib60 | 2 | c-kit, PDGFRβ | 3–65 | RECIST, 3D ORR | 17% 3D ORR |
| Selumetinib69 NCT01362803 |
1,2 | MEK | 3–18 | Toxicity, PK, 3D ORR | MTD defined, 3D ORR in 100% of first cohort reported69; phase 2 opening 2015 |
| Cediranib NCT00326872 |
2 | VEGFR-1,-2,-3 | ≥18 | 3D ORR | Ongoing |
| Vinblastine/Methotrexate NCT00030264 |
2 | cytotoxic | ≤25 | TTP | Ongoing |
| Everolimus NCT01412892 |
2 | mTOR | 18–60 | 3D ORR | Ongoing |
| Everolimus NCT01365468 |
2 | mTOR | >10 | 3D ORR, TTP | Ongoing |
| Nilotinib NCT01275586 |
2 | c-kit, BCR-ABL, MAPK11, PDGFRβ | ≥18 | REIST; 3D ORR | Ongoing |
| Celecoxib; PEG-Interferon alpha 2b NCT00846430 |
2 | Immune; Angiogenesis | 2–30 | Symptom improvement and RECIST | Ongoing |
| PLX3397 NCT02390752 |
1,2 | c-kit, CSF1R and FLT3 | 3–31 | Toxicity, PK, PD, ORR | Ongoing |
| Selumetinib NCT02407405 |
2 | MEK | ≥18 | Toxicity, PK, 3D ORR | Ongoing |
| PD-0325901 NCT02096471 |
2 | MEK | ≥16 | 3D, ORR | Ongoing |
| Trametinib NCT02124772 |
1 | MEK | 1 m–17 | Toxicity, PK, PD | Pending |
| Cabozantinib NCT02101736 |
2 | VEGFR, c-Met, RET | ≥16 | 3D, ORR | Ongoing |
| Sunitinib NCT01402817 |
2 | PDGFR, VEGFR, c-kit | 3–65 | 3D ORR | Suspended |
Abbreviations: 3D ORR, volumetric objective radiographic response; BCR-ABL, fusion gene of breakpoint cluster region and Abl1; c-kit, Kit ligand or stem cell factor; c-MET, MET proto-oncogene or hepatocyte growth factor receptor; CSF1R, colony stimulating factor 1 receptor; FLT3, Fms-like tyrosine kinase 3; MAPK11, mitogen-activated protein kinase 11; MEK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PD, pharmacoodynamic; PDGF/R, platelet-derived growth factor/receptor; PK, pharmacokinetics; Raf, serine/threonine-protein kinase; RECIST, Response Evaluation Criteria In Solid Tumors; RET, rearranged during transfection proto-oncogene; TTP, time to progression; VEGF, vascular endothelial growth factor; WHO ORR, World Health Organization objective response rate.