临床试验/NCT04455594

NCT04455594尚未招募2 期

Almonertinib Vs. Erlotinib/Chemotherapy for Neo-adjuVant Treatment of Stage IIIA-N2 EGFR-mutated NSCLC: a Multicenter, Open-label, Phase II Randomized Controlled Trial

The First Affiliated Hospital of Guangzhou Medical University1 个研究点分布在 1 个国家目标入组 168 人开始时间: 2020年10月最近更新: 2020年7月2日

适应症

干预措施

试验速览

阶段: 2 期
状态: 尚未招募
发起方
入组人数: 168
试验地点: 1
主要终点: Objective response rate (ORR)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multicenter, randomized, controlled, phase II study assessing the efficacy and safety of Almonertinib compared Erlotinib or platinum doublet chemotherapy (carboplatin or cisplatin + pemetrexed) as neoadjuvant therapy to EGFRm+ IIIA-N2 NSCLC patients.

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 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Male or female, age at least 18 years, no more than 75 years.
•Previously untreated, histologically documented NSCLC with completely or potentially resectable IIIA-N2 nonsquamous NSCLC(according to Version 8 of AJCC staging). N2 is defined as as radiologically and pathologically confirmed, nonbulky metastases to single-station mediastinal lymph nodes (lymph nodes < 2 cm in short axis) that are expected to be completely resectable.
•Tumor tissue samples or blood samples are confirmed as EGFR sensitive mutations by central laboratory tests (including Ex19del or L858R, both alone or with other EGFR mutations). If the tumor tissue is accessible, the tumor tissue is recommended to be submitted for examination. If tumor tissue is not accessible or patient cannot undergo tissue biopsy, blood sample is also allowed.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
•At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumour assessment scans are done at least 14days afar the screening biopsy is performed.
•Women of childbearing potential must use a contraception method during the study treatment and for at least 3 months after the treatment is completed; must have a negative pregnancy test prior to starting treatment or proved no risk of pregancy by meeting one of the following criteria:
•Postmenopausal defined as age 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 considered 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 postmenopausal range for the laboratory.
•Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
•Male patients should be willing to use barrier contraception (i.e., condoms) during the study treatment and for at least 3 months after the treatment is completed.
•Signed and dated informed consent form.

排除标准

•Treatment with any of the following:
•Prior surgical resection of lung cancer.
•Prior treatment with any EGFR TKI.
•Prior treatment with any chemotherapy for NSCLC
•Prior treatment with any radiotherapy for NSCLC
•Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
•Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug.
•Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
•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.
•Patients with malignant pleural effusion. [only exception: pleural effusion on CT scan (not visible on CXR) or considered too small and pericardial effusion]
•Patients who received yellow-fever vaccine or other attenuated live vaccine during pemetrexed treatment.
•Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or 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 such as active infection. Screening for chronic conditions is not required.
•Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to swallow the study drug, or previous significant bowel resection that would preclude adequate absorption of Almonertinib.
•Any of the following cardiac criteria:
•Mean resting corrected QT interval (QTc) > 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
•Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 ms).
•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 prolong the QT interval.
•Left ventricular ejection fraction (LVEF) <= 40%.
•History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease.
•Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values:
•Absolute neutrophil count (ANC) < 1.5 x 10^9 / L;
•Platelet count <100 x 10^9 / L;
•Hemoglobin < 90 g/L (<9 g/dL);
•Alanine aminotransferase > 2.5 x upper limit of normal (ULN).
•Aspartate aminotransferase (AST) > 2.5 x ULN.
•Total bilirubin (TBL) > 1.5 x ULN or > 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia).
•Creatinine > 1.5 x ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 x ULN.
•Women at breastfeeding or have a negative serum or urine pregnancy test in the 3 days prior to the start of the treatment..
•History of hypersensitivity to any active or inactive ingredient of Almonertinib, or to drugs with a similar chemical structure or class to Almonertinib.
•History of hypersensitivity to any active or inactive ingredient of Erlotinib, or to drugs with a similar chemical structure or class to Erlotinib.
•With lactose in the tablets, patients with rare genetic disease like galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use use erlotinib.
•Patients who are allergic to pemetrexed or any other component of the preparation, carboplatin or cisplatin.
•Patients with contraindications of pemetrexed and carboplatin or cisplatin.
•Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
•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.
•Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

研究组 & 干预措施

Investigator-choice therapy (Erlotinib or Chemotherapy)

Active Comparator

Erlotinib 150mg QD or Cisplatin(75mg/m2) or Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles

干预措施: Erlotinib (Drug)

Almonertinib

Experimental

Almonertinib 110mg QD

干预措施: Almonertinib (Drug)

Investigator-choice therapy (Erlotinib or Chemotherapy)

Active Comparator

Erlotinib 150mg QD or Cisplatin(75mg/m2) or Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles

干预措施: Cisplatin (Drug)

Investigator-choice therapy (Erlotinib or Chemotherapy)

Active Comparator

Erlotinib 150mg QD or Cisplatin(75mg/m2) or Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles

干预措施: Carboplatin (Drug)

Investigator-choice therapy (Erlotinib or Chemotherapy)

Active Comparator

Erlotinib 150mg QD or Cisplatin(75mg/m2) or Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles

干预措施: Pemetrexed (Drug)

结局指标

主要结局

Objective response rate (ORR)

时间窗: From date of randomization to an average of 6 weeks after the first dose

Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.

次要结局

R0 resection rate(Up to 1 week after surgery)
Downstaging rate(From date of randomization to an average of 12 weeks after the first dose)
Major Pathological Response (MPR)(From date of randomization to an average of 12 weeks after the first dose)
Concordance of EGFRm status between plasma-derived ctDNA(Baseline, up to 1 week before surgery and up to 1 week after surgery)
Disease free survival (DFS)(From date of randomization up to approximately 18 months after date of resection)
Pathological complete response (pCR)(From date of randomization to an average of 12 weeks after the first dose)
Overall Survival (OS)(Up to approximately 5.5 years after the last patient is randomized)
Incidence of Adverse Events (AEs)(Up to 80 weeks)

研究者

发起方

The First Affiliated Hospital of Guangzhou Medical University

申办方类型

Other

责任方

Principal Investigator

主要研究者

Jianxing He

Chief Surgeon

The First Affiliated Hospital of Guangzhou Medical University

研究点 (1)

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