EGFR Gene Mutation Clinical Trial
Official title:
A Phase I/Ib Study of Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
This phase I/Ib trial studies the side effects and best dose of alisertib when given together with osimertinib in treating patients with EGFR-mutated stage IV lung cancer. Alisertib may stop the growth of tumor cells by blocking a specific protein (Aurora Kinase A) that researchers believe may be important for the growth of lung cancer. Osimertinib may reduce tumor growth by blocking the action of a certain mutant protein (EGFR). This study may help researchers test the safety of alisertib at different dose levels in combination with osimertinib, and to find out what effects, good and/or bad, it has on EGFR-mutated lung cancer.
PRIMARY OBJECTIVE: I. To determine the safety and tolerability of combination treatment with alisertib and osimertinib in patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) who have progressed on osimertinib monotherapy and to identify a recommended phase 2 dose for the combination. SECONDARY OBJECTIVES: I. To provide preliminary efficacy data for the combination of alisertib and osimertinib in metastatic EGFR-mutant lung cancer patients who have progressed on osimertinib monotherapy. II. To determine whether pre-treatment Targeting Protein for XKlp2 (TPX2) positivity by immunohistochemistry (IHC) correlates with response to alisertib + osimertinib combination therapy. III. To evaluate the pharmacokinetics of alisertib in combination with osimertinib. IV. To evaluate the central nervous system (CNS) response rate of alisertib + osimertinib. V. To provide preliminary efficacy data for the combination of alisertib and osimertinib in metastatic EGFR-mutant lung cancer patients without known TP53 tumor genomic alterations who have progressed on osimertinib monotherapy. EXPLORATORY (CORRELATIVE) OBJECTIVES: I. To identify tumor co-occurring genomic alterations that correlate with response to alisertib + osimertinib treatment. II. To determine whether phosphorylated (phospho)-aurora kinase A (AURKA) levels correlate with response to alisertib + osimertinib treatment. III. To determine whether tumor nuclear factor kappa B (NF-κB) activity correlates with response to alisertib + osimertinib treatment. IV. To evaluate for changes in circulating tumor deoxyribonucleic acid (ctDNA) during treatment with combination alisertib + osimertinib. V. To identify mechanisms of resistance to alisertib + osimertinib. VI. Safety in East Asian vs. Non-East Asian population. VII. Pharmacokinetics in East Asian vs. Non-East Asian. OUTLINE: This is a dose-escalation study of alisertib. Patients receive alisertib orally (PO) twice daily (BID) on days 1-3, 8-10, and 15-17. Patients also receive osimertinib PO once daily (QD) on days 1-28. Cycles repeat every 28 days the absence of clinical benefit, intolerance, or other contraindication to study treatment.. After completion of study treatment, patients are followed up every 3 to 6 months for up to 2 years. ;
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