Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.
Khyati N Shah, Roma Bhatt, Julia Rotow...
https://pubmed.ncbi.nlm.nih.gov/30478424Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID04085315
A Phase I/Ib Study of Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
Led by Collin Blakely · Updated on 2024-06-10
38
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
C
Collin Blakely
Lead Sponsor
P
Puma Biotechnology, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the side effects and best dose of alisertib when given together with osimertinib in patients with stage IV non-small cell lung cancer that has a specific EGFR gene mutation. This phase I/Ib trial aims to test the safety of combining these two drugs and to explore how they affect tumor growth, especially in patients who have progressed while on osimertinib alone. The study also investigates how different genetic markers in tumors might relate to treatment response and resistance. Participants receive alisertib orally twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle, alongside daily oral osimertinib. The dose of alisertib will be adjusted to find the best tolerated level, starting at 30 mg twice daily. Patients continue osimertinib at the standard dose of 80 mg daily throughout. Treatment continues until there is no clinical benefit or unacceptable side effects. After treatment ends, participants are followed every 3 to 6 months for up to 2 years. During the study, patients undergo regular assessments including imaging scans to monitor tumor response, blood tests to check drug levels and side effects, and tissue biopsies for genetic testing. Researchers will measure safety outcomes like dose-limiting toxicities and serious adverse events, as well as efficacy measures such as overall response rate, progression-free survival, and disease control rate. The study also examines changes in tumor DNA circulating in the blood and brain disease control. Participants are monitored closely to track the effects and safety of the drug combination over time.
CONDITIONS
Brief Title
Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Patients must have histologically confirmed stage IV non-small cell lung cancer.
- Male or female patients 18 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Documented activating EGFR mutation on tumor or cell-free DNA sample.
- Measurable disease by RECIST 1.1 criteria.
- Adequate blood counts and organ function within 7 days before first dose.
- Willing to provide blood and tissue samples for research.
- Willing to undergo pre-treatment biopsy or provide archived tissue.
- Female patients must be postmenopausal, surgically sterile, or agree to effective contraception or abstinence.
- Male patients must agree to effective contraception or abstinence.
- Voluntary written consent given before study procedures.
- Currently receiving and tolerating osimertinib 80 mg daily with no grade 2 or greater adverse events.
- Evidence of disease progression on recent imaging within 30 days.
- Resolution of acute toxic effects of prior treatments to grade 2 or less.
- Additional cohort-specific criteria apply depending on study group.
You will not qualify if you...
- Radiation therapy to more than 25% of bone marrow.
- Prior allogeneic bone marrow or organ transplantation.
- Known gastrointestinal disease or surgery affecting alisertib absorption.
- Inability to swallow oral medication or comply with treatment.
- Uncontrolled sleep apnea or other conditions causing excessive daytime sleepiness.
- Requirement for constant proton pump inhibitors, H2 antagonists, or pancreatic enzymes during study.
- Recent serious heart conditions or abnormal ECG.
- Pregnant or breastfeeding women.
- Intent to donate eggs or sperm during or shortly after study.
- Severe acute or chronic medical or psychiatric conditions affecting safety or study results.
- Recent diagnosis or treatment of another malignancy within 3 years (with exceptions).
- Current treatment with contraindicated medications affecting QT interval or CYP3A4.
- Unstable or leptomeningeal CNS metastases.
- Cohort-specific exclusions including certain genetic mutations and prior treatments.
AI-Screening
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Repeated 28-day cycles until lack of clinical benefit or intolerable toxicity
Participants receive combination treatment with alisertib and osimertinib. Alisertib is taken orally twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle. Osimertinib is taken orally once daily on days 1-28. Treatment cycles repeat every 28 days until lack of clinical benefit, intolerable toxicity, or other contraindications.
Multiple visits during each 28-day cycle for dosing and assessments
Follow-up
Duration - Up to 2 years
After completing study treatment, participants are followed up every 3 to 6 months for up to 2 years to monitor safety and long-term outcomes.
Visits every 3 to 6 months
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
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Research Team
L
Lisa Tan
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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