Non-Small Cell Lung Cancer
Conditions
Interventions
treatment group:Osimertinib
control group:First-generation EGFR-TKIs/Osimertinib
Sponsors
Hangzhou Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Participants must have Histological confirmation of advanced non small cell lung cancer, with activating epidermal growth factor receptor ,treating with First-generation EGFR-TKIs, without progression according to RECIST1.1, with T790M mutation detected by droplet digital PCR (ddPCR) or CODAR-ARMS PCR in blood samples; 2. Participants must be aged = 18 years; 3. Life expectancy of >= 12 months; 4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1; 5. Participants must have normal organ and marrow function as defined below: absolute neutrophil count =1,500/mcL; platelets =100,000/mcL; hemoglobin >9.0 g/dL; total bilirubin < 1.5 times the ULN if no liver metastases or < 3 times the ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases; AST(SGOT)/ALT(SGPT) <2.5 × institutional upper limit of normal or <5 times the ULN in the presence of liver metastases; creatinine = 1.5 x institutional upper limit of normal OR creatinine clearance =50 mL/min as determined by the Cockcrft-Gault formula; 6. Female patients: Must not be pregnant or breast-feeding. Women of child-bearing potential must have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: 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 are considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and 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; 7. Participants must be =2 weeks since any major surgery (excluding vascular access placement, mediastinoscopy, or biopsies performed by an interventional service); 8. Participants must be =2 weeks since any prior radiation, including CNS radiation; 9. Male patients: Willing to use adequate contraception (barrier or abstinence) while on treatment with study drug and for 3 months after finishing treatment; 10. Female patients: Willing to use adequate contraception (barrier or abstinence) at least 2 weeks before receiving any study medication, while on treatment with study drug, and for 3 months after finishing treatment. 11. Provide informed written consent according to GCP; 12. Willing to return to enrolling institution for follow-up; 13. Willing to provide tissue and blood samples for correlative research purposes.
Exclusion criteria
Exclusion criteria: 1. Evidence of bleeding diathesis or coagulopathy; 2. Participants get disease progression according to RECIST1.1 before trial; 3. participants with rare mutations and mixed mutations on EGFR; 4. Evidence of central nervous system involvement or brain metastases confirmed by head CT or brain MRI within 28 days prior to being registered for protocol therapy; 5. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration for protocol therapy; 6. Anticipation of need for major surgical procedure during the course of the study; 7. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to registration for protocol therapy; 8. Refractory nausea and vomiting, chronic gastrointestinal diseases, previous significant bowel resection, or any process that compromises the ability to swallow or absorb oral medication; 9. Significant medical history or unstable medical comorbidities, including: heart disease including congestive heart failure (NYHA Grade II or greater); unstable angina; prior myocardial infarction (NSTEMI or STEMI) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of >150 mm Hg or diastolic blood pressure of >100 mm Hg while on antihypertensive medication; any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, QT interval corrected by Fridericia's formula (QTcF) of >/= 450 ms in males or >/= 470 ms in females; any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval and listed in Appendix B that a patient is unable to stop; past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease; 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; active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Screening for chronic conditions is not required. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with osimertinib; left ventricular ejection fraction of < 45%; 10. Any evidence of severe or uncontrolled systemic diseases, including 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; 11. Ophthalmological conditions as follows: Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion; Uncontrolled glaucoma (irrespective of IOP); 12. Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry; 13. Pregnant women are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Brain progression;OS; | — |
Countries
China
Contacts
Public ContactQing Zhao
Hangzhou Cancer Hospital
Outcome results
None listed