Mutations are changes in DNA, the genetic material that serves as the body’s instruction book. Some of genetic mutations result in uncontrolled cellular replication and subsequently tumor formation. This phase I trial studies the side effects of osimertinib, carboplatin, cisplatin, and etoposide in treating patients with EGFR, RB1, and P53 mutant non-small cell lung cancer that has spread to other places in the body (metastatic). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, cisplatin, or etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving osimertinib, carboplatin, cisplatin, and etoposide may work better at treating non-small cell lung cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT03567642.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. Determine the safety and toxicity profile of combination osimertinib, platinum (cisplatin or carboplatin), etoposide for patients with metastatic EGFR mutant lung cancers with concurrent RB1 and TP53 alterations.
SECONDARY OBJECTIVES:
I. Measure overall response rate (complete response [CR] + partial response [PR]).
II. Measure progression-free survival.
III. Measure overall survival.
CORRELATIVE OBJECTIVES:
I. Perform next-generation sequencing based mutation testing on tumors before treatment, prior to chemotherapy add in and at progression.
II. Perform next-generation sequencing based mutation testing on circulating-free deoxyribonucleic acid (cfDNA) before treatment, prior to chemotherapy add in, after completion of chemotherapy, with every radiologic assessment and at progression.
III. Assess for biomarkers that may predict for certain resistance mechanisms, such as small cell histologic transformation.
OUTLINE: This is a dose-escalation study of cisplatin, carboplatin, and etoposide.
Patients receive osimertinib orally (PO) on days 1-21. Beginning in cycle 4, patients also receive etoposide intravenously (IV) on days 1-3 and cisplatin or carboplatin IV on day 1 for 4 cycles. From cycle 8 onward, osimertinib monotherapy will be continued. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorHelena A. Yu
