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Central Nervous System Committee updates from the Children’s Oncology Group Fall Investigator Meeting (September 5-8, 2023)

The Children’s Oncology Group (COG) is a National Cancer Institute-supported organization focused on clinical trials for pediatric and adolescent cancer and including representatives from over 200 children’s hospitals.  Since the previous COG investigator meeting in fall 2022, two new clinical trials for pediatric and AYA patients have opened.

  • ACNS2021 is a phase 2 study for patients 3-29 years old with localized pineal and/or suprasellar CNS non-germinomatous germ cell tumor; subjects receive 6 cycles of chemotherapy followed by response-based whole ventricular and spinal canal radiation.
  • ACNS2031 is a phase 3 study for patients 4-21 years old with low or average-risk medulloblastoma; the study will evaluate the impact of sodium thiosulfate on cisplatin-induced ototoxicity in all subjects and craniospinal dose reduction in patients with clinico-molecularly-defined low-risk disease.
Currently enrolling COG clinical trials for patients with CNS tumors:
  • Any newly diagnosed primary CNS tumor
    • APEC14B1-MCI (Molecular Characterization Initiative): Provides free comprehensive clinical molecular testing—paired tumor/normal whole exome sequencing, DNA methylation array, and RNA fusion panel, enrolling ages 0-25 years
      • Part of the NCI-funded Childhood Cancer Data Initiative
  • High grade glioma (HGG)
    • ACNS1822: phase 1/2 study of Selinexor concurrent with radiation therapy and as maintenance therapy for patients with non-metastatic HGG including DIPG and non-pontine DMG, enrolling ages 1-21 years old
      • Excludes tumors harboring BRAFV600E or IDH1 mutations
    • ACNS1723: phase 2 study of Dabrafenib and Trametinib following radiation for patients with non-metastatic BRAFV600E-mutant HGG, enrolling ages 3-21 years
    • Low grade glioma (LGG)
      • Newly-diagnosed/previously untreated: 
        • Phase 3 non-inferiority studies randomizing 2:1 to Selumetinib vs. carboplatin/vincristine
          • ACNS1831: patients with systemic NF1, enrolling ages 2-21 years old
          • ACNS1833: patients without systemic NF1, enrolling ages 2-21 years old
            • Excludes tumors with BRAFV600E mutation
      • Recurrent: 
          • ACNS1931: phase 3 study of Selumetinib or Selumetinib plus vinblastine, enrolling ages 2-25 years old 
            • Excludes patients with NF1 or tuberous sclerosis complex, tumors harboring BRAFV600E or IDH1 mutations, and subjects that previously had progressive disease while on treatment with vinblastine or a MEK inhibitor
        • Medulloblastoma
          • ACNS1422: phase 2 study for patients with newly-diagnosed average risk WNT subgroup medulloblastoma reducing craniospinal radiation and chemotherapy doses, enrolling ages 3-21 years old
        Clinical trials are being actively developed through the CNS Committee of COG for patients with high-risk childhood medulloblastoma, young child medulloblastoma, atypical teratoid/rhabdoid tumor, and CNS germinoma.  Further information can be found in the following article: Leary, S.E.S., et al., “Children’s Oncology Group’s 2023 blueprint for research: Central nervous system tumors.”  Pediatr Blood Cancer Sept 2023: S1-10.  DOI:10.1002/pbc.30600.