ArticleInvestigational new drugs2014
Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: phase 1 dose-escalation study.
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies.Journal of clinical pharmacology · 2022Trial
- A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children's Oncology Group Phase I and Pilot Consortium (ADVL0921).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
- A phase I dose escalation, dose expansion and pharmacokinetic trial of gemcitabine and alisertib in advanced solid tumors and pancreatic cancer.Cancer chemotherapy and pharmacology · 2022Article
- Simultaneous silencing Aurora-A and UHRF1 inhibits colorectal cancer cell growth through regulating expression of DNMT1 and STAT1.International journal of medical sciences · 2021Article
- Biotransformation Pathways and Metabolite Profiles of Oral [Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies.Leukemia & lymphoma · 2020Article
- The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020Review
- Inhibition of Aurora A enhances radiosensitivity in selected lung cancer cell lines.Respiratory research · 2019Article
- Targeted therapies for non-HPV-related head and neck cancer: challenges and opportunities in the context of predictive, preventive, and personalized medicine.The EPMA journal · 2019Review
- Mass balance, routes of excretion, and pharmacokinetics of investigational oral [Investigational new drugs · 2019Article
- Phase I dose-escalation study of chiauranib, a novel angiogenic, mitotic, and chronic inflammation inhibitor, in patients with advanced solid tumors.Journal of hematology & oncology · 2019Article
- Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: rationale for lower dosage in Asia.British journal of clinical pharmacology · 2018Article
- Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma.Oncotarget · 2017Article
- The Aurora kinase inhibitors in cancer research and therapy.Journal of cancer research and clinical oncology · 2016Review
- A Phase Ib Study of the combination of the Aurora Kinase Inhibitor Alisertib (MLN8237) and Bortezomib in Relapsed Multiple Myeloma.British journal of haematology · 2016Article
- A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer.Nature medicine · 2016Article
- Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors.Drugs in R&D · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThis phase 1b study evaluated an enteric-coated tablet (ECT) formulation of the investigational Aurora A kinase inhibitor, alisertib (MLN8237).
methodsPatients with advanced, non-hematologic malignancies received oral alisertib ECT for 7 d BID followed by 14 d treatment-free (21-day cycles; 3 + 3 dose escalation schema). Objectives were to assess safety, pharmacokinetics, and antitumor activity, and to define a recommended phase 2 dose (RP2D) of alisertib.
results24 patients were treated. Median age was 57 years. Patients received a median of 2 cycles (range 1-12). The RP2D was determined as 50 mg BID for 7 d (21-day cycles). A cycle 1 dose-limiting toxicity of grade 4 febrile neutropenia was observed in 1 of 13 patients at RP2D. The most common drug-related adverse event (AE) was neutropenia (50%). At doses ≥ 40 mg BID, 7 patients had drug-related AEs that were serious but largely reversible/manageable by dose reduction and supportive care, including 3 with febrile neutropenia. Pharmacokinetic data were available in 24 patients. Following administration of alisertib ECT, the plasma peak concentration of alisertib was achieved at ~3 h; systemic exposure increased with increasing dose over 10-60 mg BID. Mean t½ was ~21 h following multiple dosing. Renal clearance was negligible. Nine patients achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and 6.93* months; *censored).
conclusionsAlisertib ECT was generally well tolerated in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for 7 d and is being evaluated in ongoing phase 2 studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.