A Phase II Trial of Osimertinib and Abemaciclib With a Focus on Non-Small Cell Lung Cancer Patients With EGFR Activating Mutations With Osimertinib Resistance

University of California, San Diego1 site in 1 country18 target enrollmentNovember 21, 2020

ConditionsLung Cancer

InterventionsAbemaciclib Osimertinib

DrugsAbemaciclib Osimertinib

Overview

Phase: Phase 2
Intervention: Abemaciclib
Conditions: Lung Cancer
Sponsor: University of California, San Diego
Enrollment: 18
Locations: 1
Primary Endpoint: Progression Free Survival at 6 months
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Detailed Description

Lung cancer is the leading cause of cancer deaths. Advances in the systemic treatment of non-small cell lung cancer (NSCLC) have increased survival in metastatic EGFR-mutated NSCLC. However resistance to therapy can develop. NSCLC tumors with EGFR-activating mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors with overall response rates approximating 80%. The third generation EGFR compound osimertinib is a standard first line option. Resistance to the third generation EGFR-TKI osimertinib can develop with a median PFS of 18.9 months. Current research examining acquired resistance to EGFR-TKIs has focused on overcoming these main mechanisms of EGFR-TKI resistance and understanding the impact of co-occurring alterations. Frequently altered pathways concomitantly affected with EGFR in lung cancer are cell cycle genes. This study will explore a strategy to inhibit EGFR and CDK4/6 in resistant EGFR mutated lung cancer patients post progression on osimertinib.

Registry

clinicaltrials.gov

Start Date

November 21, 2020

End Date

December 1, 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of California, San Diego

Responsible Party

Principal Investigator

Hatim Husain

Associate Professor

University of California, San Diego

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed NSCLC-lung adenocarcinoma histology.
•Tumor must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q).
•Patient must have Stage IV, recurrent or metastatic disease with EGFR mutant disease.
•Patient must have progressive disease on or after osimertinib (any number of prior treatment is allowed).
•At least one measurable lesion according to RECIST version 1.1
•Age \>18 years
•ECOG performance status ≤1
•Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
•Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
•The patient has adequate organ function for all of the following criteria, as defined below.

Exclusion Criteria

•Chemotherapy or other investigational agent within three weeks prior to the start of study treatment.
•Radiotherapy within 4 weeks prior to randomization, except as follows:
•Palliative radiation to target organs other than chest or stereotactic radiotherapy to the chest may be allowed up to 2 weeks prior to treatment with osimertinib and abemaciclib.
•Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
•Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study.
•Known hypersensitivity to osimertinib or the excipients of any of the trial drugs.
•History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to study enrollment.
•Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 28 days after treatment has ended. \<Note: for osimertinib this must be 28 days, however this may be longer for other drugs.
•Female patients of childbearing potential who are nursing or are pregnant or are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and/or do not agree to submit to pregnancy testing required by this protocol.
•Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.