1 Introduction
1.1 Clinical classification and current treatment protocols
1.1.1 Surgical intervention
1.1.2 Radiation therapy (RT)
1.1.3 Chemotherapy
ID | Phase | Treatment | Treatment arms | Subgroup | Risk | Eligible age cohort | Allocation | Primary outcome measure | Estimated primary completion date |
---|---|---|---|---|---|---|---|---|---|
NCT01878617 | II | Treatment stratification based on both clinical risk (low-, standard-, intermediate-, or high-risk) and molecular subtype (WNT, SHH, or non-WN/non-SHH) | Low-risk (stratum W1): reduced-dose craniospinal irradiation, lower dose of cyclophosphamide | WNT (strata W): positive for WNT biomarkers | All risk categories | 3 years to 39 years | Non-randomized | Progression-free survival | 2023 |
atypical (W2): standard-dose craniospinal radiation, standard chemotherapy (cisplatin, vincristine, cyclophosphamide) | Change in VO2 peak values after aerobic training intervention; change in spatial span backward standard score | ||||||||
High-risk (W3): high does craniospinal radiation, standard chemotherapy | |||||||||
Standard-risk (S1): standard-dose craniospinal radiation, chemotherapy, vismodegib maintenance therapy for skeletally | SHH (strata S): positive for SHH biomarkers | ||||||||
High-risk (S2): high-dose craniospinal radiation, chemotherapy, vismodegib maintenance therapy for skeletally mature patients | |||||||||
Standard-risk (N1): standard-dose craniospinal radiation, chemotherapy | Non-WNT/non-SHH, failed, or indeterminate (Strata N): negative for WNT and SHH biomarkers for results are indeterminable | Progression-free survival | |||||||
intermediate risk (N2): standard-dose craniospinal radiation, standard chemotherapy (cisplatin, vincristine, cyclophosphamide) for four cycles intermixed with an additional three cycles of chemotherapy with pemetrexed and gemcitabine | Change in VO2 peak values after aerobic training intervention; change in spatial span backward standard score | ||||||||
High-risk (N3): high-dose craniospinal radiation, standard chemotherapy with an additional three cycles of chemotherapy with pemetrexed and gemcitabine | |||||||||
NCT01857453 | II | Reduced irradiation compensated by chemotherapy | Carboplatin + etoposide-based chemotherapy followed by radiation therapy with 24 Gy on the in toto neuro axis and 54 Gy on the post-operative bed | Standard-risk | 18 years to 70 years | Single group assignment | Survival without disease at 1 year | 2018 | |
NCT02025881 | I/II | Sequential high-dose chemotherapy | Carboplatin + etoposide then thiotepa then cyclophosphamide + busilvex | High-risk | Up to 5 years | Single group assignment | Phase I- maximum tolerated dose; phase II- event- free survival up to 3 years | 2018 | |
NCT02875314 | IV | Induction chemotherapy followed by either a single cycle of three tandem cycles | Single cycle (thiotepa, etoposide, and carboplatin for 6 days) | Non-WNT/non-SHH | High-risk | Up to 10 years | Randomized | Event-free survival, overall survival | 2020 |
three tandem cycles (thiotepa and carboplatin over 2 days, three cycles) | |||||||||
NCT02724579 | II | Reduced craniospinal radiotherapy | Reduced craniospinal radiotherapy (18 Gy) with a limited target volume boost to the tumor bed of 36 Gy for a total of 54 Gy and reduced chemotherapy (no vincristine during chemotherapy and reduced-dose maintenance chemotherapy) | WNT | Standard-risk | 3 years to 21 years | Single group assignment | Progression-free survival | 2025 |
NCT02066220 | II/III | Risk-specific radio- and chemotherapy | Low-risk: radiotherapy and reduced-intensity maintenance chemotherapy consisting of 3 courses of cisplatin, CCNU, and vincristine alternating with three courses of cyclophosphamide and vincristine | ẞ-catenin nuclear immunopositivity (non-metastatic) | Low- and standard- risk | 3 years to 21 years | randomized | 3-year event-free survival | 2024 |
Standard-risk: radiotherapy with carboplatin or radiotherapy without carboplatin and maintenance chemotherapy consisting of four courses of cisplatin, CCNU, and vincristine alternating with four courses of cyclophosphamide and vincristine | ẞ-catenin nuclear immunonegativity (non-metastatic) |
1.2 Molecular classifications and subgroup-specific molecular alterations
1.2.1 WNT-activated MBs
1.2.2 SHH-activated MBs
1.2.3 Group 3 and Group 4 MBs
1.3 Emerging risk stratification models
1.4 Molecular subgroup-specific treatment approaches
1.4.1 WNT-activated MBs
1.4.2 SHH-activated MBs
ID | Phase | Treatment | Subgroup | Eligible age cohort | Estimated enrollment | Estimated primary completion date | Responsible party |
---|---|---|---|---|---|---|---|
NCT00089245 | I | Intrathecal radioimmunotherapy using I-8H9 | 8H9 reactive malignancy confirmed by IHC | Child, adult, older adults | 120 | 2018 | Y-mAbs Therapeutics |
NCT02502708 | I | Indoximod, an inhibitor of the immune “checkpoint” pathway indoleamine 2,3-dioxygenase (IDO), in combination with temozolomide | 3 years to 21 years | 115 | 2019 | NewLink Genetics Corporation | |
NCT02684071 | II | Methotrexate and chemotherapy (topotecan and cyclophosphamide) | up to 21 years | 10 | 2019 | Ziad Khatib, Nicklaus Children’s Hospital f/k/a Miami Children’s Hospital | |
NCT02905110 | Early phase I | Simultaneous methotrexate/etoposide infusion | Posterior fossa tumors | 1 year to 80 years | 10 | 2020 | David Ilan Sandberg, The University of Texas Health Science Center, Houston |
NCT01661400 | Early phase I | Metronomic cyclophosphamide or thalidomide | 6 months to 21 years | 12 | 2020 | Washington University School of Medicine | |
NCT02962167 | I | Modified measles virus (MV-NIS) | 12 months to 39 years | 46 | 2020 | Sabine Mueller, MD, PhD, University of California, San Francisco | |
NCT03043391 | I | Oncolytic poliovirus (PV) immunotherapy with PVSRIPO | 12 years to 21 years | 12 | 2020 | Istari Oncology, Inc. | |
NCT02271711 | I | Autologous ex vivo-expanded NK cells | up to 21 years | 24 | 2020 | MD Anderson Cancer Center | |
NCT02359565 | I | Pembrolizumab | 1 year to 29 years | 110 | 2020 | National Cancer Institute (NCI) | |
NCT03389802 | I | APX005M, a humanized IgG1κ mAb that binds to CD40 | 1 year to 21 years | 45 | 2020 | Pediatric Brain Tumor Consortium | |
NCT03299309 | I | Cytomegalovirus (CMV)-specific peptide vaccine (PEP-CMV) | 3 years to 35 years | 30 | 2020 | Gary Archer Ph.D., Duke University | |
NCT03734913 | I | ZSP1602, a SMO protein inhibitor | 18 years to 75 years | 65 | 2020 | Guangdong Zhongsheng Pharmaceutical Co., Ltd. | |
NCT03598244 | I | Savolitinib, a small molecule inhibitor of c-Met | 6 years to 21 years | 36 | 2020 | National Cancer Institute (NCI) | |
NCT03387020 | I | Ribociclib (inhibitor of cyclin D1/CDK4 and CDK6) in combination with everolimus | 1 year to 21 years | 45 | 2020 | Pediatric Brain Tumor Consortium | |
NCT03173950 | II | Nivolumab | 18 years to 99 years | 180 | 2020 | National Institutes of Health Clinical Center (CC) (National Cancer Institute (NCI)) | |
NCT03273712 | II | 90Y-DOTA-tyr3-Octreotide for somatostatin receptor positive tumors | Tumors expressing somatostatin receptors | 6 months to 90 years | 46 | 2020 | Sue O’Dorisio, University of Iowa |
NCT02644291 | I | Mebendazole, an antihelmintic agent | 1 year to 21 years | 21 | 2021 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | |
NCT03500991 | I | HER2-Specific CAR T-cell locoregional immunotherapy | 1 year to 26 years | 36 | 2021 | Julie Park, Seattle Children’s Hospital | |
NCT02095132 | I/II | Adavosertib (MK-1775), a small molecule inhibitor of the tyrosine kinase WEE1 and irinotecan hydrochloride | 1 year to 21 years | 154 | 2021 | National Cancer Institute (NCI) | |
NCT01356290 | II | Multidrug antiangiogenic approach | up to 19 years | 40 | 2021 | Andreas Peyrl, Medical University of Vienna | |
NCT03911388 | I | G207, an oncolytic herpes simplex virus-1 (HSV) | 3 years to 18 years | 15 | 2022 | Gregory K. Friedman, MD, University of Alabama at Birmingham | |
NCT03638167 | I | EGFR806-specific CAR T-cell locoregional immunotherapy | 1 year to 26 years | 36 | 2022 | Julie Park, Seattle Children’s Hospital | |
NCT03893487 | Early phase I | Fimepinostat (CUDC-907), a small molecule inhibitor of histone deacetylase and PI3 kinase | 3 years to 39 years | 30 | 2022 | Sabine Mueller, MD, PhD, University of California, San Francisco | |
NCT03709680 | I | Palbociclib in combination with temozolomide and irinotecan | 2 years to 20 years | 100 | 2022 | Pfizer | |
NCT03904862 | I/II | CX-4945 (silmitasertib sodium), small molecule inhibitor of casein kinase II (CK2) | SHH | 3 years and older | 60 | 2022 | Pediatric Brain Tumor Consortium |
NCT02748135 | I/II | TB-403 (humanized monoclonal antibody against placental growth factor (PlGF) | 6 months to 18 years | 36 | 2022 | Oncurious NV | |
NCT03936465 | I | BMS-986158, a bromodomain (BRD) and extra-terminal domain (BET) inhibitor | Predicted increased sensitivity to BET inhibition: MYC or MYCN amplification or high copy number gain, MYC or MYCN translocation, BRD4 or BRD3 translocation | 1 year to 21 years | 34 | 2022 | Steven DuBois, Dana-Farber Cancer Institute |
NCT02650401 | I/II | Entrectinib (RXDX-101), a TRKA/B/C, ROS1, and ALK inhibitor | CNS tumors harboring- NTRK1/2/3, ROS1, ALK molecular alterations, including gene fusions | up to 22 years | 65 | 2023 | Hoffmann-La Roche |
NCT04049669 | II | Indoximod in combination with radiation and chemotherapy | 3 to 21 years | 140 | 2024 | Theodore S. Johnson, Augusta University | |
NCT03210714 | II | JNJ-42756493 (erdafitinib), an oral pan-FGFR inhibitor | Mutations in the FGFR1/2/3/4 pathway | 12 months to 21 years | 49 | 2024 | National Cancer Institute (NCI) |
NCT03213678 | II | Ly3023414 (samotolisib), a PI3K/mTOR inhibitor | TSC loss of function mutations, PI3K/MTOR activating mutations | 12 months to 21 years | 144 | 2024 | National Cancer Institute (NCI) |
NCT03213704 | II | LOXO-101 (larotrectinib) | NTRK fusions | 12 months to 21 years | 49 | 2024 | National Cancer Institute (NCI) |
NCT03213665 | II | Tazemetostat, a small molecule EZH2 inhibitor | EZH2, SMARCB1, or SMARCA4 gene mutations | 12 months to 21 years | 49 | 2024 | National Cancer Institute (NCI) |
NCT03233204 | II | Olaparib | Defects in deoxyribonucleic acid (DNA) damage repair genes | 12 months to 21 years | 49 | 2024 | National Cancer Institute (NCI) |
NCT04023669 | I | Prexasertib (LY2606368), a molecularly targeted CHK1/2 inhibitor | Group3/Group4; SHH; indeterminate | 1 year to 24 years | 100 | 2025 | St. Jude Children’s Research Hospital |
NCT03434262 | I | Ribociclib and gemcitabine | Group3/Group4 | 1 year to 39 years | 108 | 2025 | St. Jude Children’s Research Hospital |
Ribociclib and trametinib | SHH/WNT | 1 year to 39 years | 108 | 2025 | St. Jude Children’s Research Hospital | ||
Ribociclib and sonidegib | SHH | 1 year to 39 years | 108 | 2025 | St. Jude Children’s Research Hospital | ||
NCT03526250 | II | Palbociclib | Rb positive, or mutations in cell cycle genes | 12 months to 21 years | 49 | 2025 | National Cancer Institute (NCI) |
NCT03155620 | II | Treatment directed by mutation carrier screening | Based on results of molecular screening | 12 months to 21 years | 1000 | 2027 | National Cancer Institute (NCI) |