Table 1.
Clinical Trials for NF1.
| Target | Therapeutic | Children/Adults | Clinical Trial Identifier | Sponsor | Phase | Active/Recruiting/Completed | Results Posted/Reference | Study Start Date |
|---|---|---|---|---|---|---|---|---|
| Plexiform neurofibromas | ||||||||
| MEK | Selumetinib | 2Y-18Y | NCI | II | Recruiting | 2011 | ||
| >18Y | NCI | I/II | Recruiting | 2015 | ||||
| >18Y | NCI | II | Recruiting | 2015 | ||||
| MEK | PD-0325901 | >16Y | UAB | II | Active | 2014 | ||
| MEK | Binimetinib | >1Y | UAB | II | Recruiting | 2017 | ||
| MEK/B-RAF | Trametinib + Dabrafenib | 1mth-17Y | Novartis | I | Recruiting | 2015 | ||
| mTOR | Everolimus (RAD001) | 18Y-60Y | Novartis | II | Completed | 2011 | ||
| >6Y | Novartis | II | Terminated | Yes | 2012 | |||
| 2Y-65Y | EUCTR-2016–001563–36 | Novartis | II | Recruiting | 2016 | |||
| mTOR | Sirolimus | 3Y-75Y | UAB | II | Completed | [133] | 2008 | |
| c-MET, VEGFR2 | Cabozantinib | >16Y | UAB | II | Active | 2014 | ||
| KIT | Pexidartinib | 3Y-35Y | NCI | I/II | Suspended | 2015 | ||
| ABL, c-KIT, PDGFR | Imatinib Mesylate | 3Y-65Y | IU | II | Completed | [65] | 2006 | |
| <18Y | EUCTR-2009–016922–15 | HSJD | II | Active | 2009 | |||
| 2Y-65Y | EUCTR-2012–000869–21 | IRCCS | I | Active | 2012 | |||
| 3Y-65Y | IU School of Medicine | I/II | Completed | Yes | 2012 | |||
| 2Y-21Y | St. Justine’s Hospital | II | Recruiting | 2014 | ||||
| RTK: PDGFR, VEGFR, RET, CSF-1R, Flt3 | Sunitinib | 3Y-65Y | IU | II | Suspended | Yes | 2012 | |
| RTK | Nilotinib | >18Y | IU | I | Completed | Yes | 2011 | |
| JAK/Stat | Peg-Interferon alpha-2b | 2Y-30Y | SHH | II | Active | Yes | 2008 | |
| 18 mth-21Y | Univ. of Pittsburgh | II | Completed | 2006 | ||||
| TGF-beta | Pirfenidone | 18Y-70Y | Mayo Clinic | II | Completed | [134] | 2000 | |
| 3Y-21Y | NCI | I | Completed | [135] | 2002 | |||
| RAF, VEGFR, PDGFR | Sorafenib | 3Y-18Y | NCI | I | Completed | [136] | 2008 | |
| VEGFR | Cediranib | >18Y | NCI | II | Terminated | Yes | 2006 | |
| RAS | Tipifarnib | 3Y-25Y | NCI | II | Completed | [137] | 2001 | |
| DHFR inhibitor/mitosis inhibitor | Methotrexate + Vinblastine | -25Y | CHoP | II | Completed | 2001 | ||
| Photosensitizer | Talaporfin sodium (LS11) | 3Y-21Y | CHoP | I | Terminated | 2008 | ||
| 14Y-30Y | MCW | II | Recruiting | 2016 | ||||
| Cutaneous neurofibromas | ||||||||
| MEK | Selumetinib | >18Y | NCI | II | Recruiting | 2017 | ||
| VEGF-A | Ranibizumab | >18Y | MGH | I | Completed | 2008 | ||
| mTOR | Everolimus | >18Y | UTHealth | II | Completed | Yes | 2015 | |
| mTOR | Sirolimus (rapamycin) | >13Y | UTHealth | I | Completed | 2009 | ||
| Photosensitizer | Levulan (5-aminolevulinic acid) | 18Y-90Y | MCW | I | Active | 2011 | ||
| Immune response modifier | Imiquimod | >18Y | MGH | I | Completed | 2009 | ||
| MPNSTs | ||||||||
| EGFR | Erlotinib | >18Y | NCI | II | Completed | [138] | 2003 | |
| ABL, c-KIT, PDGFR | Imatinib Mesylate | >10Y | NCI | II | Completed | [139] | 2002 | |
| RAF/VEGFR | Sorafenib | >18Y | NCI | II | Completed | [140] | 2005 | |
| RTK | Dasatinib | >13Y | SARC | II | Active | [141] | 2007 | |
| AURKA | Alisertib | >18Y | NCI | II | Completed | [142] | 2012 | |
| Granulocyte - colony stimulating factor (G-CSF) | Filgrastim | All ages | NCI | II | Completed | 2005 | ||
| BET | CPI-0610 | >18Y | UTSW | II | Recruiting | 2017 | ||
| RTK, mRTOR | PLX3397 + Sirolimus | >18Y | Columbia Univ. | I/II | Recruiting | 2015 | ||
| mTOR/VEGF-A | Everolimus + Bevacizumab | >18Y | SARC | II | Active | [143] | 2012 | |
| mTOR/HSP90 | Sirolimus + Ganetespib | >16Y | SARC | I | Active | 2013 | ||
| Anti-PD-1 immunotherapy | Pembrolizumab | >18Y | EUCTR-2015–004747–39/ | Oslo Univ. Hospital | II | Recruiting | 2015/2016 | |
| Gastrointestinal Stromal Tumors (GIST) | ||||||||
| MEK | Selumetinib | >18Y | NCI | II | Recruiting | 2017 | ||
| All tumors | ||||||||
| MEK | Binimetinib | >18Y | Array BioPharma | II | Completed | 2013 | ||
| MEK | Cobimetinib | 6 mth-30Y | Hoffmann-La Roche | I/II | Recruiting | 2016 | ||
| Neuroendocrine tumors | ||||||||
| RTK PDGFR, VEGFR, RET, CSF-1R, Flt3/mTOR | Sunitinib + Everolimus | >18Y | NCI | II | Recruiting | 2015 | ||
| Optic Pathway Glioma | ||||||||
| Anti-angiogenic | Lenalidomide | <21Y | NCI | II | Active | 2012 | ||
| Anti-angiogenic and anti-myeloma cell growth | Pomalidomide | 3Y-20Y | NCI | I | Active | 2015 | ||
| Low-Grade Gliomas | ||||||||
| RAF, VEGFR, PDGFR | Sorafenib | >2Y | NYUSM | II | Terminated | [144] | 2011 | |
| MEK | Selumetinib | 3Y-21Y | NCI | I/II | Recruiting | 2010 | ||
| MEK | Binimetinib | 1Y-18Y | CHLA | I/II | Recruiting | 2016 | ||
| EGFR/mTOR | Erlotinib + Sirolimus | <21Y | CRI | I | Completed | 2007 | ||
| mTOR | Everolimus | 1Y-21Y | UAB | II | Active | 2011 | ||
| Cytotoxic | Carboplatin + Vincristine | <9Y | NCI | III | Completed | [145] | 1997 | |
| Cytotoxic | Carboplatin + Vinblastine | <21Y | COG | I | Completed | 2006 | ||
| Mitosis inhibitor/RTK | Vinblastine + Nilotnib | <65Y | EUCTR-2012–003005–10 | Gustave Roussy | I/II | Active | 2012 | |
| Juvenile Myelomonocytic Leukemia | ||||||||
| TNF-alpha | Etanercept | 6mth-18Y | M.D. Anderson | II | Terminated | Yes | 2004 | |
| Cognition | ||||||||
| Dopamine–norepinephrine reuptake inhibitor | Methylphenidate | 7Y-12Y | Hospices Civils de Lyon | IV | Completed | [146] | 2004 | |
| HMG-CoA reductase inhibitor | Lovastatin | 8Y-15Y | UAB | II | Active | [120] | 2009 | |
| HMG-CoA reductase inhibitor | Simvastatin | <18Y | EUCTR-2009–010965–22 | Erasmus MC | III | Completed | [147, 148] | 2009 |
| Na-channel blocker | Lamotrigine | <18Y | EUCTR-2013–003405–26 | Erasmus MC | II | Active | 2013 | |
| 12Y-18Y | Erasmus MC | II | Recruiting | 2014 | ||||
| Autism | ||||||||
| HMG-CoA reductase inhibitor | Simvastatin | <18Y | EUCTR-2012–005742–38 | CMFT | II | Completed | [149] | 2012 |
| Bone deficits | ||||||||
| Vitamin D supplement | Cholecalciferol | 25Y-40Y | University of Utah | II | Recruiting | 2017 | ||
| Recombinant human bone morphogenetic protein-2 | rhBMP-2 | 2Y-18Y | UAB | II | Recruiting | 2016 | ||
| <18Y | EUCTR-2007–003835–22 | HCL | III | Active | 2008 |
Drug therapies in clinical trials are listed for specific NF1 complications including their molecular targets. Children/Adults refers to age of participants eligible for trial. The clinical trial identifier refers to either that of either NIH ClinicalTrials.gov or the European Clinical Trials Database (EudraCT). Sponsor abbreviations: University of Alabama at Birmingham (UAB), Massachusetts General Hospital (MGH), Children’s Hospital of Philadelphia (CHoP), Medical College of Wisconsin (MCW), Indiana University (IU), Spectrum Health Hospitals (SHH), The University of Texas Health Science Center at Houston (UTHealth), University of Texas Southwestern Medical Center (UTSW), Sarcoma Alliance for Research through Collaboration (SARC), NYU School of Medicine (NYUSM), The Foundation of the Carlo Besta Neurological Institute, IRCCS, Italy (IRCCS), Hospital Sant Joan de Deu (HSJD), Erasmus Medical Center (Erasmus MC), Children’s Hospital Los Angeles (CHLA), Children’s Research Institute (CRI), Novartis Pharmaceuticals (Novartis), Children’s Oncology Group (COG), MD Anderson Cancer Center (MD Anderson), Central Manchester University Hospitals NHS Foundation Trust (CMFT), Hospices Civils de Lyon (HCL).