{"doi":"10.1002/pbc.31619","title":"Phase I Study of Vorinostat and Temsirolimus in Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>Diffuse intrinsic pontine glioma (DIPG) carries a poor prognosis with a median survival of less than 12 months. Key molecular features include histone H3 mutation (K27M) and AKT pathway dysregulation. There is currently no curative treatment.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>\n                      This is a Phase I study of vorinostat and temsirolimus in newly diagnosed (Stratum 1) and progressive (Stratum 2) DIPG (NCT02420613). The primary aims are to determine the safety, maximum tolerated dose (MTD), and toxicities. A modified 3 + 3 design was used to establish the MTD, where the first three patients were assigned the first dose level regardless of stratum. Stratum 1 received radiotherapy with vorinostat, followed by up to 10 cycles of vorinostat and temsirolimus. Stratum 2 received up to 12 cycles of vorinostat and temsirolimus. Vorinostat was administered at a fixed dose of 230 mg/m\n                      <jats:sup>2</jats:sup>\n                      daily on Days 1–8, and temsirolimus was administered on Days 1 and 8 at 25 mg/m\n                      <jats:sup>2</jats:sup>\n                      (Dose level 1) or 35 mg/m\n                      <jats:sup>2</jats:sup>\n                      (Dose level 2).\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      Six patients were enrolled, three in each stratum. No dose‐limiting toxicity was observed, and most adverse effects were limited to Grades 1 or 2, including fatigue, myelosuppression, hyperlipidemia, hyperglycemia, elevated creatinine, nausea, vomiting, and headache. One patient experienced Grade 3 leukopenia. In the study, the MTD with acceptable toxicity was vorinostat 230 mg/m\n                      <jats:sup>2</jats:sup>\n                      and temsirolimus 35 mg/m\n                      <jats:sup>2</jats:sup>\n                      .\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Overall, the combination of temsirolimus and vorinostat is well‐tolerated and safe, prompting the need for larger studies to investigate its efficacy.</jats:p>\n                  </jats:sec>","journal":"Pediatric Blood &amp; Cancer","year":2025,"id":609573,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"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":1390792,"name":"Muhammad Usman Baig","orcid":"0000-0003-1809-1249","position":1,"is_corresponding":false},{"id":344491,"name":"Joya Chandra","orcid":"0000-0002-2077-9715","position":2,"is_corresponding":false},{"id":1566857,"name":"Suzanne McGovern","orcid":null,"position":3,"is_corresponding":false},{"id":288903,"name":"Arnold C. Paulino","orcid":"0000-0002-0269-3045","position":4,"is_corresponding":false},{"id":1566858,"name":"Leena M. Ketonen","orcid":null,"position":5,"is_corresponding":false},{"id":382773,"name":"Soumen Khatua","orcid":"0000-0001-6416-650X","position":6,"is_corresponding":false},{"id":344490,"name":"Wafik Zaky","orcid":"0000-0002-7079-8105","position":7,"is_corresponding":false},{"id":1001725,"name":"Lea Stitzlein","orcid":"0000-0002-8119-5609","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phase I Study of Vorinostat and Temsirolimus in Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>Diffuse intrinsic pontine glioma (DIPG) carries a poor prognosis with a median survival of less than 12 months. Key molecular features include histone H3 mutation (K27M) and AKT pathway dysregulation. There is currently no curative treatment.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>\n                      This is a Phase I study of vorinostat and temsirolimus in newly diagnosed (Stratum 1) and progressive (Stratum 2) DIPG (NCT02420613). The primary aims are to determine the safety, maximum tolerated dose (MTD), and toxicities. A modified 3 + 3 design was used to establish the MTD, where the first three patients were assigned the first dose level regardless of stratum. Stratum 1 received radiotherapy with vorinostat, followed by up to 10 cycles of vorinostat and temsirolimus. Stratum 2 received up to 12 cycles of vorinostat and temsirolimus. Vorinostat was administered at a fixed dose of 230 mg/m\n                      <jats:sup>2</jats:sup>\n                      daily on Days 1–8, and temsirolimus was administered on Days 1 and 8 at 25 mg/m\n                      <jats:sup>2</jats:sup>\n                      (Dose level 1) or 35 mg/m\n                      <jats:sup>2</jats:sup>\n                      (Dose level 2).\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      Six patients were enrolled, three in each stratum. No dose‐limiting toxicity was observed, and most adverse effects were limited to Grades 1 or 2, including fatigue, myelosuppression, hyperlipidemia, hyperglycemia, elevated creatinine, nausea, vomiting, and headache. One patient experienced Grade 3 leukopenia. In the study, the MTD with acceptable toxicity was vorinostat 230 mg/m\n                      <jats:sup>2</jats:sup>\n                      and temsirolimus 35 mg/m\n                      <jats:sup>2</jats:sup>\n                      .\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Overall, the combination of temsirolimus and vorinostat is well‐tolerated and safe, prompting the need for larger studies to investigate its efficacy.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40000388","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/pbc.31619","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pbc.31619","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Brain Stem Neoplasms","Sirolimus","Antineoplastic Combined Chemotherapy Protocols","Follow-Up Studies","Maximum Tolerated Dose","Adolescent","Child","Child, Preschool","Female","Male","Vorinostat","Diffuse Intrinsic Pontine Glioma"],"keywords":["Diffuse Intrinsic Pontine Glioma (Dipg) | H3 K27m‐mutant Glioma | Phase I Clinical Trial | Targeted Therapy"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T10:01:56.934532Z","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":[]}