An Open-label, Two-arm, Multicenter, Phase II Randomized Controlled Trial Assessing the Impact of Olanzapine on the Efficacy of First-line Immunotherapy in Patients With Advanced EGFR Mutation-negative Non-small Cell Lung Cancer (NSCLC).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- The Overall Survival（OS）
研究概览
简要总结
Clinical Trial
The objective of this clinical trial is to determine whether antidepressant medications, such as olanzapine, in combination with immune checkpoint inhibitors are more effective than the use of immune checkpoint inhibitors alone. The main questions it aims to answer are:
Is the combination therapy of antidepressant medication with immune checkpoint inhibitors more efficacious than the therapy with immune checkpoint inhibitors alone? What medical issues might participants encounter when treated with the combination of antidepressant medication and immune checkpoint inhibitors?
Participants will:
Take olanzapine in combination with immune checkpoint inhibitors or immune checkpoint inhibitors alone for 2 months.
Visit the clinic for check-ups and tests every two weeks, and have follow-up visits every six weeks after the treatment ends.
Keep a record of their symptoms and disease progression.
详细描述
An Open-label, Two-arm, Multicenter, Phase II Randomized Controlled Study on the Impact of Olanzapine on the Efficacy of First-line Immunotherapy in Patients with Advanced EGFR Mutation-negative Non-small Cell Lung Cancer (NSCLC).
Primary Research Objective:
To evaluate the objective response rate (ORR) in patients with advanced EGFR mutation-negative NSCLC treated with first-line PD-1/PD-L1 inhibitors combined with olanzapine.
Secondary Research Objectives:
To evaluate the interval of progression-free survival (iPFS) in patients with advanced EGFR mutation-negative NSCLC treated with first-line PD-1/PD-L1 inhibitors combined with olanzapine.
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
- •Participants voluntarily enroll in this study and sign an informed consent form, with good compliance and cooperation with follow-up.
- •Age is over 18 years old (including 18 years old) and under 75 years old (including 75 years old).
- •ECOG score: 0-2 points.
- •Expected survival is no less than 3 months.
- •Staged as Stage IV according to the TNM system.
- •Histologically or cytologically confirmed EGFR mutation-negative non-small cell lung cancer.
- •Has not received systemic antitumor treatment, and is intended to receive monotherapy or combined chemotherapy with a PD-1/PD-L1 inhibitor as first-line treatment.
- •Normal major organ function, that is, meeting the following criteria: (1) Hematological examination criteria must be met: Hb≥90 g/L; ANC≥1.5×10^9/L; PLT≥80×10^9/L. (2) Biochemical examination must meet the following criteria: TBIL<1.5×ULN; ALT and AST<2.5×ULN; serum Cr≤1.25×ULN or endogenous creatinine clearance > 45 ml/min (Cockcroft-Gault formula).
- •Women of childbearing age must have taken reliable contraceptive measures and have undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and are willing to use appropriate methods of contraception during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate methods of contraception during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization.
排除标准
- •Have received any of the following treatments:
- •Previously used any EGFR tyrosine kinase inhibitors;
- •Previously received any chemotherapy for lung cancer;
- •Previously received any radiotherapy for lung cancer (except palliative radiotherapy for bone metastases);
- •Within 4 weeks prior to the first administration of the study drug, the subject had undergone major surgery;
- •Within 7 days prior to the first administration of the study drug, used strong inhibitors or inducers of CYP3A
- •Subjects with concurrent other malignant tumors, except for basal cell carcinoma of the skin and in situ cancer.
- •Subjects with uncontrollable malignant pleural effusion and pericardial effusion.
- •Subjects allergic to contrast agents for CT and MRI or any subjects who cannot tolerate MRI examination.
- •As judged by the investigator, any serious or poorly controlled systemic diseases, such as uncontrolled hypertension, active bleeding diathesis, or active infection.
- •Clinically severe gastrointestinal functional abnormalities that may affect the intake, transport, or absorption of the drug, such as the inability to take oral medication, uncontrollable nausea or vomiting, history of extensive gastrointestinal resection, unresolved recurrent diarrhea, atrophic gastritis, gastric diseases requiring long-term use of proton pump inhibitors, Crohn's disease, ulcerative colitis, etc.
- •Hepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis.
- •Meet any of the following cardiac examination results:
- •The average of the corrected QT interval (QTcF) obtained from three ECG examinations at rest is > 470 msec;
- •Resting ECG suggests conduction or ECG morphological abnormalities (such as complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, and PR interval > 250 msec, etc.);
- •There are any factors that increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concurrent medication of unexplained sudden death in direct relatives under the age of 40 or prolonged QT interval;
- •Left ventricular ejection fraction (LVEF) < 50%.
- •Insufficient bone marrow reserve or organ function, reaching any of the following laboratory limits:
- •Absolute neutrophil count <1.5×10^9/L;
- •Platelet count <100×10^9/L;
- •Hemoglobin <90 g/L (<9 g/dL);
- •If there is no definite liver metastasis, alanine aminotransferase > 3 times the upper limit of normal (ULN); if there is liver metastasis, alanine aminotransferase > 5×ULN;
- •If there is no definite liver metastasis, aspartate aminotransferase >3×ULN; if there is liver metastasis, aspartate aminotransferase > 5×ULN;
- •If there is no definite liver metastasis, total bilirubin > 1.5×ULN; or with Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total bilirubin > 3×ULN;
- •Creatinine > 1.5×ULN and creatinine clearance <50 mL/min (calculated by the Cockcroft-Gault formula); creatinine clearance is only required if creatinine > 1.5×ULN;
- •Serum albumin (ALB) <28 g/L.
- •Active fungal, bacterial, and/or viral infections requiring systemic treatment.
- •Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
- •History of interstitial lung disease, drug-induced interstitial lung disease, history of radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
- •Subjects who, in the judgment of the investigator, may have poor compliance with the procedures and requirements of the study, such as subjects with a clear history of neurological or mental disorders, currently suffering from mental disorders, etc.
- •Subjects whom the investigator judges to have any condition that endangers the safety of the subject or interferes with the evaluation of the study.
研究组 & 干预措施
Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group
Receiving first-line treatment with a PD-1/PD-L1 inhibitor as a single agent or in combination with chemotherapy (according to the instructions manual)，Medication is administered on the first day of each cycle, with one cycle every 3 weeks. A continuous 21-day treatment constitutes one treatment cycle.Then receive olanzapine orally at a dose of 5mg once daily (qd), with continuous administration for 6-8 weeks.
干预措施: Olanzapine (Drug)
Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group
Receiving first-line treatment with a PD-1/PD-L1 inhibitor as a single agent or in combination with chemotherapy (according to the instructions manual)，Medication is administered on the first day of each cycle, with one cycle every 3 weeks. A continuous 21-day treatment constitutes one treatment cycle.Then receive olanzapine orally at a dose of 5mg once daily (qd), with continuous administration for 6-8 weeks.
干预措施: Nivolumab (Drug)
Group Without Olanzapine
Receiving first-line treatment with a PD-1/PD-L1 inhibitor as a single agent or in combination with chemotherapy (according to the instructions manual)，Medication is administered on the first day of each cycle, with one cycle every 3 weeks. A continuous 21-day treatment constitutes one treatment cycle..
干预措施: Nivolumab (Drug)
结局指标
主要结局
The Overall Survival（OS）
时间窗: 24 months
The Overall Survival（OS），From the time of a patient's diagnosis or the commencement of treatment, to the time of the patient's death.
次要结局
未报告次要终点