{"doi":"10.1002/cam4.1171","title":"Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update","abstract":"<jats:title>Abstract</jats:title><jats:p>Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early‐phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged &lt;18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase <jats:styled-content style=\"fixed-case\">II</jats:styled-content>. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (<jats:styled-content style=\"fixed-case\">ORR</jats:styled-content>) for patients with medulloblastoma in phase I/II studies was 0% (0–100) and 6.5% (0–50), respectively. Temozolomide containing regimens had a median <jats:styled-content style=\"fixed-case\">ORR</jats:styled-content> of 16.5% (0–100). Smoothened inhibitors trials had a median <jats:styled-content style=\"fixed-case\">ORR</jats:styled-content> of 8% (3–8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs.</jats:p>","journal":"Cancer Medicine","year":2017,"id":612609,"datarank":0.5806801516361837,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"self_citation_contribution":0.5806801516361837,"citation_network_contribution":0.0,"self_endowment_contribution":0.5806801516361837,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1577439,"name":"Victoria Fioravantti","orcid":null,"position":1,"is_corresponding":false},{"id":746030,"name":"Teresa de Rojas","orcid":"0000-0001-7749-8423","position":2,"is_corresponding":false},{"id":236640,"name":"Fernando Carceller","orcid":"0000-0003-3094-3758","position":3,"is_corresponding":false},{"id":1577442,"name":"Luis Madero","orcid":null,"position":4,"is_corresponding":false},{"id":1577443,"name":"Alvaro Lassaletta","orcid":null,"position":5,"is_corresponding":false},{"id":305846,"name":"Lucas Moreno","orcid":"0000-0002-0708-1670","position":6,"is_corresponding":false},{"id":1147697,"name":"Francisco Bautista","orcid":"0000-0002-0421-8862","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update","abstract":"<jats:title>Abstract</jats:title><jats:p>Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early‐phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged &lt;18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase <jats:styled-content style=\"fixed-case\">II</jats:styled-content>. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (<jats:styled-content style=\"fixed-case\">ORR</jats:styled-content>) for patients with medulloblastoma in phase I/II studies was 0% (0–100) and 6.5% (0–50), respectively. Temozolomide containing regimens had a median <jats:styled-content style=\"fixed-case\">ORR</jats:styled-content> of 16.5% (0–100). Smoothened inhibitors trials had a median <jats:styled-content style=\"fixed-case\">ORR</jats:styled-content> of 8% (3–8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs.</jats:p>","is_dataset_classified":null,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28980418","pmcid":"PMC5673921","openalex_id":"https://openalex.org/W2762453909","authors":[],"funders":[{"funder_name":"National Institute on Handicapped Research","grant_id":"","title":null}],"total_grants":1,"fwci":1.534,"citation_percentile":0.8373494,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":7},{"year":2020,"count":11},{"year":2021,"count":12},{"year":2022,"count":6},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.1171","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.1171","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcam4.1171","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.1171","host_type":"publisher"},{"url":"https://doi.org/10.1002/cam4.1171","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28980418","host_type":"repository"},{"url":"https://repositoriosaludmadrid.es/handle/20.500.12530/30195","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5673921","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5673921","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5673921?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Glioma Diagnosis and Treatment","Histone Deacetylase Inhibitors Research","Cancer Genomics and Diagnostics","Adolescent","Angiogenesis Inhibitors","Antineoplastic Combined Chemotherapy Protocols","Cerebellar Neoplasms","Child","Clinical Trials, Phase I as Topic","Clinical Trials, Phase II as Topic","Dacarbazine","Humans","Medulloblastoma","Molecular Targeted Therapy","Smoothened Receptor","Temozolomide"],"mesh_terms":["Smoothened Receptor","Temozolomide","Adolescent","Antineoplastic Combined Chemotherapy Protocols","Cerebellar Neoplasms","Child","Dacarbazine","Humans","Medulloblastoma","Clinical Trials, Phase I as Topic","Clinical Trials, Phase II as Topic","Angiogenesis Inhibitors","Molecular Targeted Therapy"],"keywords":["Medulloblastoma","Temozolomide","Medicine","Clinical trial","Oncology","Context (archaeology)","Internal medicine","Phases of clinical research","Chemotherapy","Cancer research","Biology","Children","Phase 1","Phase 2","Relapse Or Refractory Tumor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T04:14:07.686099Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}