Clinical trial · Interventional
Alisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies
A Phase 1 Dose Escalation Study of MLN8237, an Aurora A Kinase Inhibitor, in Adult Patients With Nonhematological Malignancies, Followed by a Phase 2 of MLN8237 in Lung, Breast, Head and Neck, or Gastroesophageal Malignancies
NCT01045421CI-TRIAL-00023488completedPhase 1 / Phase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is an open-label, multicenter study with a phase 1 dose escalation portion and a 2-stage, phase 2 portion, investigating MLN8237 (alisertib) in patients with advanced nonhematological malignancies.
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Nonhematological Malignancies | — | UNRESOLVED | — |
| Gastroesophageal Adenocarcinoma | — | UNRESOLVED | — |
| Head and Neck Squamous Cell Carcinoma | Head and Neck Squamous Cell Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Metastatic Breast Cancer | Malignant Breast Neoplasm | CURATED_BROADER | 0.78 |
| Non-Small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
| Small Cell Lung Cancer | Lung Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| MLN8237 (Alisertib) | Drug | Alisertib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- MLN8237 (Alisertib)
- description
- MLN8237 administered as an enteric-coated tablet (ECT)
- interventionNames
- Drug: MLN8237 (Alisertib)
Primary outcomes (2)
- measure
- Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
- timeFrame
- Phase 1: Cycle 1 Day 1 to Cycle 2 Day 21
- description
- Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. DLT defined as any of the following considered related to alisertib by investigator: Grade 4 neutropenia (absolute neutrophil count \<500 cells/cubic meter \[cells/mm\^3\]) for \>7 days; Grade 4 neutropenia with coincident fever; Grade 4 thrombocytopenia (platelets \<25,000 cells/mm3) for \>7 days; Platelet count \<10,000 cells/mm3; Grade 3 thrombocytopenia with clinically significant bleeding; Delay in initiation of the subsequent therapy cycle by \>7 days due to treatment-related toxicity; \>=Grade 3 nonhematological toxicity except \>=Grade 3 nausea/emesis occurred in the absence of optimal antiemetic therapy; \>=Grade 3 diarrhea occurred in the absence of optimal supportive therapy with loperamide/comparable antidiarrheal; Grade 3 fatigue for \<1 week; Other Grade 3 nonhematological toxicity that could be safely, reliably controlled to \<=Grade 2 with appropriate treatment.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the study: * 18 years or older * Histologically or cytologically confirmed metastatic and/or advanced solid tumor (Phase 1 only) * Phase 2 requires Non-small cell lung cancer (NSCLC); Small-cell lung cancer; Breast adenocarcinoma (female patients only); Squamous cell cancer of the head and neck (HNSCC); or Gastroesophageal adenocarcinoma * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse * Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse * Voluntary written consent * Wiling to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures * Measurable disease (Phase 2 only) Exclusion Criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: * Female patients who are pregnant or lactating * Serious medical or psychiatric illness that could interfere with protocol completion * Receipt of more than 2 previous cytotoxic chemotherapeutic regimens (4 previous regimens for breast cancer). There is no limit on the number of prior noncytotoxic therapies * Prior treatment with Aurora A-targeted agents, including MLN8237 * Prior treatment with high-dose chemotherapy * Prior allogeneic bone marrow or other organ transplant * Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to first dose of MLN8237 * Symptomatic brain metastasis * Radiotherapy to greater than 25% of bone marrow * Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected * Myocardial infarction within 6 months of enrollment * Uncontrolled cardiovascular condition * Major surgery within 14 days of first dose of MLN8237 * Active infection requiring systemic therapy, or other serious infection * Inability to swallow oral medication * Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C * Patients requiring full systemic anticoagulation * History of uncontrolled sleep apnea syndrome * Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 and during the study
References
Publications (2)
- DERIVEDMelichar B, Adenis A, Lockhart AC, Bennouna J, Dees EC, Kayaleh O, Obermannova R, DeMichele A, Zatloukal P, Zhang B, Ullmann CD, Schusterbauer C. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015 Apr;16(4):395-405. doi: 10.1016/S1470-2045(15)70051-3. Epub 2015 Feb 27. PMID 25728526
- DERIVEDFalchook G, Kurzrock R, Gouw L, Hong D, McGregor KA, Zhou X, Shi H, Fingert H, Sharma S. Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: phase 1 dose-escalation study. Invest New Drugs. 2014 Dec;32(6):1181-7. doi: 10.1007/s10637-014-0121-6. Epub 2014 Jun 1. PMID 24879333