NCT04085315

Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer

A Phase I/Ib Study of Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Collin Blakely · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Lung Cancer Metastatic
• EGFR Gene Mutation

Interventions

Type	Name	Description
DRUG	Osimertinib	Osimertinib is a medication used to treat non-small-cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. Patients will be receiving full dose osimertinib (80 mg PO daily) as part of the patient's current standard of care.
DRUG	Alisertib	Alisertib is an orally available selective aurora A kinase inhibitor. Alisertib will be administered to eligible patients in combination with osimertinib at doses ranging from 20 mg to 50 mg PO twice daily on days 1-3, 8-10, and 15-17 of a 28-day cycle. The starting alisertib dose for Cohort 1 will be 30 mg twice daily (dose level 1).

Timeline

• Start date: 2019-11-12
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2019-09-11
• Last updated: 2024-06-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study