NCT04769388已完成2 期
The Efficacy and Safety of Osimertinib Plus Carboplatin and Pemetrexed Versus Osimertinib Monotherapy in Metastatic EGFRm NSCLC Patients With EGFRm Persistence in ctDNA at 3 Weeks After 1L Osimertinib: A Multicenter, Randomized Controlled Study
Beijing Cancer Prevention & Treatment Society1 个研究点 分布在 1 个国家目标入组 80 人开始时间: 2021年12月28日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
This is a prospective, randomised, open-label, positive-controlled study to investigate the efficacy and safety of Osimertinib plus Carboplatin/Pemetrexed versus Osimertinib monotherapy in metastatic EGFRm NSCLC patients with EGFRm persistence in ctDNA at 3 weeks after first-line therapy with Osimertinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision and signed of informed consent prior to any study specific procedures;
- •Male or female, aged at least 18 years;
- •Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
- •Newly diagnosed, and histologically documented metastatic non-squamous NSCLC with sensitizing EGFR mutations positive, and classified as stage IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy;
- •Life expectancy of at least 3 months at recruitment;
- •Only the patients receiving osimertinib as 1L treatment and meeting the following criteria will be considered:
- •A. Prior to 1L osimertinib:
- •History of EGFRm (exon 19 deletion or exon 21 L858R) in the plasma ctDNA by the local testing methods.
- •No previous systemic treatment. Adjuvant therapies, or definitive radiation/chemoradiation are permitted as long as treatment was completed at least 6 months prior to receiving 1L treatment.
- •Patients with asymptomatic and stable CNS metastases for at least 2 weeks will be allowed, including leptomeningeal metastases.
- •B. Prior to randomization: Patients after 3 weeks of 1L osimertinib treatment who have persistence ctDNA EGFRm by SuperARMS at 3 weeks will be considered to be enrolled. They will need to further meet the criteria below before randomization:
- •Patients without disease progression by RECIST 1.1 evaluation;
- •At least 1 measurable extracranial lesion according to RECIST 1.1 .
- •Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential.
- •Male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
排除标准
- •Involvement in the planning and/or conduct of the study;
- •History of hypersensitivity to active or inactive excipients of Osimertinib and/or Pemetrexed and/or Carboplatin or drugs with a similar chemical structure or class to Osimertinib and/or Pemetrexed and/or Carboplatin;
- •For patients, inability to collect plasma samples at baseline and disease progression;
- •QT prolongation or any clinically important abnormalities in rhythm;
- •Any evidence of severe or uncontrolled systemic diseases;
- •Currently receiving medications or herbal supplements known to be strong inducers of CYP3A4;
- •Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1 at the time of starting study treatment.
- •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.
- •Inadequate bone marrow reserve or organ function;
- •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.
- •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.
- •Contraindication for osimertinib, pemetrexed and carboplatin according to China approved label.
- •Women who are pregnant or breast-feeding.
研究组 & 干预措施
Osimertinib 80 mg QD and platinum-based chemotherapy
Experimental
Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
干预措施: Osimertinib (Drug)
Osimertinib 80mg QD
Active Comparator
All patients randomized into this will only receive Osimertinib 80mg.
干预措施: Osimertinib (Drug)
Osimertinib 80 mg QD and platinum-based chemotherapy
Experimental
Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for up to 6 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
干预措施: Pemetrexed/Carboplatin (Drug)
结局指标
主要结局
Progression free survival
时间窗: The primary analysis of Progression-free survival (PFS) based on investigator assessment will occur when PFS maturity is observed at approximately 30 months after the first patient is randomized.
Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
次要结局
- OS rate at 18 months(The OS rate at 18 months will be defined as the Kaplan-Meier estimate of OS at 18 months.)
- Safety and tolerability: Adverse event(Safety and tolerability analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.)
- Objective Response Rate (ORR)(Objective Response Rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.)
- Disease Control Rate (DCR)(Disease control rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.)
- Duration of Response (DoR)(Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.)
- Depth of Response(Depth of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.)
- Molecular resistance mechanism(Molecular resistance mechanism analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 30 months from the first patient being randomized.)
研究者
研究点 (1)
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