Viewing Study NCT02759835



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Last Modification Date: 2024-10-26 @ 12:01 PM
Study NCT ID: NCT02759835
Status: COMPLETED
Last Update Posted: 2024-06-07
First Post: 2016-04-06

Brief Title: Local Ablative Therapy for Treatment of Oligoprogressive EGFR-Mutated Non-Small Cell Lung Cancer After Treatment With Osimertinib
Sponsor: National Cancer Institute NCI
Organization: National Institutes of Health Clinical Center CC

Study Overview

Official Title: A Pilot Study of Local Ablative Therapy for Treatment of Oligoprogressive EGFR-mutated Non-Small Cell Lung Cancer NSCLC After Treatment With Osimertinib AZD9291 Tagrisso
Status: COMPLETED
Status Verified Date: 2024-05
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: Background

Some non-small-cell lung cancers NSCLC have a mutation in a gene that makes a protein called EGFR This particular cancer can be treated with certain drugs such as erlotinib Tarceva gefitinib Iressa and osimertinib Tagrisso But many tumors become resistant to these drugs because of a second mutation Researchers want to test if adding local ablative therapy LAT extends the benefits of the drug osimertinib LAT can include techniques such as surgery radiofrequency ablation cryotherapy or radiation therapy

Objective

To test if re-taking osimertinib after LAT is safe tolerable and effective for people whose NSCLC has progressed after initial treatment with osimertinib

Eligibility

Adults ages 18 and older with certain types of NSCLC Participants will be divided into various groups as described below

Design

Participants will be screened with

Medical history

Physical exam

Blood urine and heart tests

Tumor scans

Eye exam

Review of tumor sample

Participants will take the study drug by mouth once a day They will continue until they can no longer tolerate it or their disease worsens They will keep a dosage diary

All participants will start each 21-day course with physical exam blood urine and saliva tests and electrocardiogram They will have scans every 6 weeks and echocardiogram every 3 months

Groups 1 and 2 will

Start osimertinib right away

Have LAT if their disease progresses and is suitable for LAT If LAT cannot be performed or LAT consists of a procedure other than surgery a tumor biopsy will be performed

Re-start osimertinib after LAT or other treatments if not suitable for LAT

Group 3 will

Have LAT

If LAT consists of a procedure other than surgery a tumor biopsy will be performed

Start osimertinib after LAT

After participants stop taking the drugs they will have a final visit This will include

Medical history

Physical exam

Blood tests

Participants will be called every year for follow-up
Detailed Description: Background

Epidermal growth factor receptor EGFR tyrosine kinase inhibitors TKI have significantly improved the response rate RR and survival in patients with tumors harboring EGFR-sensitizing mutations
An invariable consequence of treatment with EGFR-TKIs is the development of acquired resistance The most common mechanism of resistance observed in approximately 50 of all cases in patients treated with 1st and 2nd generation EGFR-TKIs is the emergence of a secondary mutation T790M in exon 20
Osimertinib is a 3rd-generation EGFR-TKI designed to target the T790M mutation which has shown impressive responses in both first- and second-line settings
Despite these developments it is almost certain that selection pressure will lead to the emergence of newer clones that are resistant to treatment with osimertinib One common mechanism of acquired resistance to osimertinib is the generation of EGFR C797S mutation
The use of local ablative therapies for patients who develop limited metastatic disease or oligoprogressive disease on EGFR-TKI therapy is promising
We hypothesize that following local ablative therapy to treat oligoprogressive disease after emergence of resistance osimertinib can be resumed safely and re-initiation of osimertinib results in additional progression-free survival benefits

Objectives

Determine the safety tolerability and efficacy as assessed by progression free survival PFS upon re-initiation of osimertinib following local ablative therapy LAT for patients with oligoprogressive disease after treatment with osimertinib
Assess mechanisms of acquired resistance to osimertinib

Eligibility

Histologically confirmed advanced lung adenocarcinoma with EGFR-sensitizing somatic mutations or a germline T790M mutation and no prior EGFR tyrosine kinase inhibitor TKI therapy Cohort 1 OR progressive disease after 1st or 2nd generation EGFR TKI therapy harboring somatic T790M mutation Cohort 2 or patients with progressive disease after treatment with osimertinib who are eligible for local ablative therapy Cohort 3 If biopsy for EGFR mutation status confirmation is not clinically feasible EGFR mutations may be confirmed by circulating tumor deoxyribonucleic acid ctDNA analysis using a Clinical Laboratory Improvement Amendments of 1988 CLIA certified assay
Presence of measurable disease per Response Evaluation Criteria in Solid Tumors RECIST version 11
Eastern Cooperative Oncology Group ECOG performance status 0-2
Adequate end organ function
If patients are not eligible for LAT they will be referred for standard of care chemotherapy as per treating physicians discretion These patients may also be considered for other clinical trials

Design

This is a single-institution open-label phase II trial of osimertinib treatment in EGFR mutant lung cancer
Eligible patients not previously treated with osimertinib will be treated with osimertinib daily until disease progression At the time of progression patients with oligoprogressive disease no more than 5 sites of progressive disease will be assessed for LAT
If patients are eligible for LAT osimertinib will be resumed after LAT and they will be followed for second progression on osimertinib PFS2
If patients progress at the same site where LAT has been performed before the progression will be considered to be a result of inadequate ablation and they will be considered for repeat LAT and again re-challenged with osimertinib if clinically feasible
Tumor samples will be obtained at baseline by a mandatory biopsy At the time of first progression on osimertinib if a patient is eligible for surgery as a form of LAT then a tissue sample will be obtained for genomic and proteomic studies to identify mechanisms of acquired resistance For patients who are not eligible for LAT or a form of LAT that is not surgery radiation radiofrequency ablation cryoablation then a mandatory biopsy will be performed if clinically safe to obtain tissue for above studies
Re-treatment will be allowed for a small number of subjects

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: True
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: False
Is an FDA AA801 Violation?: None
Secondary IDs
Secondary ID Type Domain Link
16-C-0092 None None None