Status and phase
Conditions
Treatments
About
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.
Full description
Background:
Objectives:
Eligibility:
Design:
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
For inclusion in the study subjects should fulfill the following criteria:
Provision of informed consent prior to any study specific procedures
Patients (male/female) must be greater than or equal to 18 years of age.
Patients with histologically confirmed, by the National Cancer Institute (NCI) Laboratory of Pathology or by Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified Next Generation Sequencing or Cobas estimated Epidermal Growth Factor Receptor (EGFR) Mutation Test v1/2 at an outside institution, advanced lung adenocarcinoma with EGFR-sensitizing somatic mutations or a germline T790M mutation (detected histologically or via circulating tumor deoxyribonucleic acid (ctDNA) analysis using a CLIA assay) with:
OR
-- Progressive disease after 1st or 2nd generation EGFR TKI therapy harboring somatic T790M mutation (Cohort 2)
OR
Progressive disease after treatment with osimertinib who are eligible for local ablative therapy (Cohort 3)
Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing Hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
EXCLUSION CRITERIA:
Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception, of alopecia and grade 2, prior platinum-therapy related neuropathy.
Treatment with an investigational drug within five half-lives of the compound.
Major thoracic or abdominal surgery from which the patient has not sufficiently recovered yet.
Untreated and uncontrolled second tumor in the past 2 years.
Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of cytochrome P450 3A4 (CYP3A4) (at least 3 weeks prior) will only be eligible at the PI's discretion.
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
Patients with central nervous system (CNS) metastases who are neurologically unstable.
Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Any of the following cardiac criteria
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents
Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
Primary purpose
Allocation
Interventional model
Masking
37 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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