To Evaluate the Efficacy and Safety of High-Dose Almonertinib Versus Osimertinib in the Second-Line Treatment of Patients With EGFR Mutations in Advanced NSCLC With Brain Metastases: a Multicenter, Randomized Controlled, Double-Blind Clinical Trial
Overview
- Phase
- Phase 3
- Intervention
- Almonertinib
- Conditions
- NSCLC
- Sponsor
- Shanghai Chest Hospital
- Enrollment
- 232
- Primary Endpoint
- Intracranial progression-free survival (IPFS) in patients with advanced NSCLC with brain metastases treated with high-dose Almonertinib versus Osimertinib in second-line treatment with positive EGFR T790M mutation.
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a multicenter, randomized controlled, double-blind clinical trial. The study is designed to evaluate the efficacy and safety of high-dose Almonertinib versus Osimertinib in the second-line treatment of patients with EGFR mutations in advanced NSCLC with brain metastases.
Detailed Description
This is a multicenter, randomized controlled, double-blind clinical study which will recruit about 232 patients in China. The study is designed to evaluate the efficacy and safety of high-dose Almonertinib versus Osimertinib in the second-line treatment of patients with EGFR mutations in advanced NSCLC with brain metastases. Target Patient Population:Age 18 years or older with histologically or cytologically proven advanced NSCLC with brain parenchymal (BM) metastases.The patient was laboratory confirmed to be EGFR T790M mutation positive at or after progression of 1/2 generation EGFR-TKI therapy. Test Drug, Dosage and Medication Regimen:Almonertinib will be administered orally at a dose of 165 mg per time, Q.D.If a patient cannot tolerate a dose of 165mg due to adverse reactions, when the adverse reactions restore to level 1 (CTCAE 5.0) or below, the dosage could be adjusted to 110mg per day, Q.D. Osimertinib will be administered orally at a dose of 80 mg per time, Q.D. If a patient cannot tolerate a dose of 40mg due to adverse reactions, when the adverse reactions restore to level 1 (CTCAE 5.0) or below, the dosage could be adjusted to 40mg per day, Q.D.
Investigators
Lu Shun
Chief physician
Shanghai Chest Hospital
Eligibility Criteria
Inclusion Criteria
- •1.18 ≤ age and above.
- •Histology or cytology is confirmed as NSCLC, imaging confirmed as advanced NSCLC with brain metastasis (including relapsed or newly diagnosed advanced patients after previous surgical treatment; according to AJCC eighth edition lung cancer staging standard).
- •Progressed after receiving first or second generation EGFR-TKI treatment, T790M positive.
- •According to RECIST1.1, the patient has at least 1 intracranial target lesion and 1 extracranial target lesion. The requirements for target lesions are: measurable lesions that have not undergone local treatment such as irradiation or have clearly progressed after local treatment, with the longest diameter at baseline ≥10 mm (if it is a lymph node, the maximum short diameter is required to be ≥15 mm).
- •The brain condition is stable for at least 2 weeks before the study drug treatment, without any systemic (oral or parenteral) corticosteroid or anticonvulsant drug treatment. Non-absorbable corticosteroids can be used locally and inhaled according to the indications.
- •The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and there is no deterioration at least 2 weeks before the study drug treatment, and the expected survival period is not less than 12 weeks.
- •Female patients of childbearing age are willing to take appropriate contraceptive measures from signing the informed consent to 6 months after the last treatment with the study drug and should not breastfeed; male patients are willing from signing the informed consent to 6 months after the last treatment with the study drug Use barrier contraception (ie condoms).
- •Female patients of childbearing age must have a negative serum or urine HCG test within 7 days before enrollment in the study, and they must be non-lactating.
- •9.The subjects themselves participated voluntarily and signed a written informed consent form.
Exclusion Criteria
- •Have received any of the following treatments:
- •Within 4 weeks before the first administration of the study drug, the patient has undergone major surgery (such as craniotomy, thoracotomy, or laparotomy, etc.), or underwent minor traumatic surgery (biopsy, bronchoscopy, and Thoracic drainage). The definition of major surgery refers to the level 3 and level 4 surgery specified in the "Administrative Measures for the Clinical Application of Medical Technology" in Appendix H, which was implemented on November 1, 2018;
- •Except for patients who have received local radiotherapy (palliative radiotherapy for bone in non-target lesions) within 2 weeks before the first administration of the study drug; within 4 weeks before the first administration of the study drug, they have received more than 30% bone marrow irradiation (calculated area of bone marrow) See Annex I), or received extensive radiotherapy; received whole brain radiotherapy due to this disease before enrollment;
- •Recurrence within 6 months after adjuvant or neoadjuvant treatment for early lung cancer; if there is both neoadjuvant therapy and adjuvant therapy, the adjuvant treatment time will be calculated;
- •There is pleural effusion/peritoneal effusion that requires clinical intervention (patients who do not need to drain the effusion or who are stable for 2 weeks or more after drainage can be included); there is pericardial effusion (a small amount of pericardium that is stable for 2 weeks or more) Fluid effusion is allowed to enter the group). If anti-tumor drugs have been used locally (such as chest cavity perfusion) during drainage, at least 5 drug half-lives or 21 days (whichever is shorter) must be eluted before the first administration of the study treatment before being included in the group;
- •Within 7 days before the first administration of the study drug, have used CYP3A4 strong inhibitors, strong inducers or drugs with a narrow therapeutic window of sensitive substrates, or need to continue to receive these drugs during the study period (see Appendix E for the list of drugs);
- •Are receiving drugs that are known to prolong the QT interval or may cause torsades de pointes, or need to continue to receive these drugs during the study period (see Appendix E for the drug list and washout time);
- •Within 4 weeks before the first administration of the study drug, the five half-lives of the study drug as a subject participating in other clinical trials or still in other clinical trials, whichever is longer (except for screening failure).
- •Mixed SCLC and mixed NSCLC, large cell neuroendocrine carcinoma and sarcomatoid carcinoma confirmed by histology or cytology.
- •At the beginning of the study drug treatment, there is a residual toxicity of the previous anti-tumor treatment that is greater than CTCAE level 1 that has not been relieved, except for hair loss and level 2 neurotoxicity caused by the previous anti-tumor. In the past, intracranial hemorrhage unrelated to the tumor occurred.
Arms & Interventions
Almonertinib
Almonertinib will be administered orally at a dose of 165 mg per time, Q.D.
Intervention: Almonertinib
Osimertinib
Osimertinib will be administered orally at a dose of 80 mg per time, Q.D.
Intervention: Osimertinib
Outcomes
Primary Outcomes
Intracranial progression-free survival (IPFS) in patients with advanced NSCLC with brain metastases treated with high-dose Almonertinib versus Osimertinib in second-line treatment with positive EGFR T790M mutation.
Time Frame: 36 months
To evaluate the efficacy of high dose Almonertinib versus Osimertinib by IRC(RECIST 1.1).
Secondary Outcomes
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(36 months)