{"doi":"10.1093/noajnl/vdaa124","title":"Phase I/II study of sorafenib in combination with erlotinib for recurrent glioblastoma as part of a 3-arm sequential accrual clinical trial: NABTC 05-02","abstract":"BACKGROUND: Receptor tyrosine kinases such as epidermal growth factor receptors (EGFRs) and their downstream signaling pathways such as the Ras-Raf-mitogen-activated protein kinase (MAPK) pathway play important roles in glioblastoma (GBM). This study investigated the safety, pharmacokinetics, and efficacy of sorafenib (Ras/Raf/MAPK inhibitor) in combination with erlotinib (EGFR inhibitor) for treatment of recurrent GBMs. METHODS: Patients with recurrent GBM were eligible. A novel sequential accrual trial design was used, where patients were sequentially accrued into separate treatment arms in phase I and phase II investigations to optimize recruitment efficiency. In phase I, a standard 3 + 3 format was used to identify dose-limiting toxicities (DLTs), determine maximum tolerated dose (MTD), and investigate pharmacokinetics. Phase II followed a 2-stage design with the primary endpoint being 6-month progression-free survival (PFS6). RESULTS: Sixteen patients were recruited for phase I, and the MTD was determined to be sorafenib 200 mg twice daily and erlotinib 100 mg once daily. DLTs include Grade 3 hypertension, Grade 3 elevated liver transaminases, and Grade 4 elevated lipase. While erlotinib did not affect sorafenib levels, sorafenib reduced erlotinib levels. In phase II, 3 of 19 stage 1 participants were progression free at 6 months. This did not meet the predetermined efficacy endpoint, and the trial was terminated. CONCLUSION: This study identified the MTD and DLTs for sorafenib and erlotinib combination therapy for recurrent GBMs; however, efficacy data did not meet the primary endpoint. This study also demonstrates the feasibility of a novel sequential accrual clinical trial design that optimizes patient recruitment for multiarm studies, which is particularly effective for multicenter clinical trials.","journal":"Neuro-Oncology Advances","year":2020,"id":68725,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":364121,"name":"John G. Kuhn","orcid":"0000-0002-7359-8643","position":1,"is_corresponding":false},{"id":133420,"name":"Kathleen R. Lamborn","orcid":null,"position":2,"is_corresponding":false},{"id":364122,"name":"Lauren E. Abrey","orcid":"0009-0002-2035-2540","position":3,"is_corresponding":false},{"id":281418,"name":"Lisa M. DeAngelis","orcid":"0000-0002-6290-7818","position":4,"is_corresponding":false},{"id":318783,"name":"Frank S. Lieberman","orcid":"0000-0003-2577-3336","position":5,"is_corresponding":false},{"id":133424,"name":"H. Ian Robins","orcid":null,"position":6,"is_corresponding":false},{"id":247466,"name":"Susan M. Chang","orcid":"0000-0003-3521-364X","position":7,"is_corresponding":false},{"id":365488,"name":"W.K. Alfred Yung","orcid":null,"position":8,"is_corresponding":false},{"id":364123,"name":"Jan Drappatz","orcid":"0000-0001-8187-7119","position":9,"is_corresponding":false},{"id":259435,"name":"Minesh P. Mehta","orcid":"0000-0002-4812-5713","position":10,"is_corresponding":false},{"id":364124,"name":"Victor A. Levin","orcid":"0000-0003-3909-2101","position":11,"is_corresponding":false},{"id":13200,"name":"Kenneth Aldape","orcid":"0000-0001-5119-7550","position":12,"is_corresponding":false},{"id":72414,"name":"Janet Dancey","orcid":null,"position":13,"is_corresponding":false},{"id":290639,"name":"John J Wright","orcid":null,"position":14,"is_corresponding":false},{"id":32675,"name":"Michael D. Prados","orcid":"0000-0002-9630-2075","position":15,"is_corresponding":false},{"id":247467,"name":"Timothy F. Cloughesy","orcid":"0000-0002-8656-7483","position":16,"is_corresponding":false},{"id":25299,"name":"Patrick Y. Wen","orcid":"0000-0002-0774-7700","position":17,"is_corresponding":false},{"id":109755,"name":"Mark R. Gilbert","orcid":"0000-0003-2556-9722","position":18,"is_corresponding":false},{"id":364120,"name":"Huanwen Chen","orcid":"0000-0003-2455-748X","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T21:41:52.279368Z","pmid":"33235994","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":[]}