A Phase II, Randomized, Open-label Trial of Trilaciclib Prior to Chemotherapy Plus Tislelizumab as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 132
- 主要终点
- incidence of grade ≥3 Neutrophil count decreased
研究概览
简要总结
The purpose of this study is to explore the myeloprotective effects of trilaciclib in advanced squamous non-small cell lung cancer patients receiving a combination therapy of chemotherapy(carboplatin+paclitaxel) and immune checkpoint inhibitor (tislelizumab), as well as enhancing antitumor efficacy and possible immunological synergies.
详细描述
This is a phase 2 clinical trial that is randomized, controlled, multicenter, and prospective in design. A total of 132 patients with advanced, untreated squamous non-small cell lung cancer will be randomly assigned 1:1 to receive or not receive Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction). Following induction, patients will receive or not receive trilaciclib with tislelizumab for every 3 weeks until PD, intolerable toxicity, withdrawal, or death. If subsequent chemotherapy is indicated for patients after first-line progression, trilaciclib will be provided to observe the myeloprotective effect in second-line treatment. The study is expected to commence recruitment in mainland China in about May 2023. It is expected that the trial will end in December 2025.
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
- •Age ≥ 18 years old and ≤ 75 years old, male or female;
- •Unresectable stage ⅢB and Ⅳ squamous non-small cell lung cancer confirmed by histology or cytology;
- •Have not received systemic anti-tumor therapy for advanced tumors in the past;
- •There is at least one measurable lesion that meets the RECIST1.1 criteria;
- •Patients with asymptomatic brain metastases or stable symptoms after treatment of brain metastases;
- •Laboratory tests meet the following criteria: Hemoglobin ≥ 100 G/L (female), 110 G/L (male) Neutrophil count ≥ 2 × 10^9/L Platelet count ≥ 100 × 10^9/L; Creatinine ≤ 15 mg/L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula); Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 3 × ULN or ≤ 5 × ULN (for patients with liver metastases); Albumin ≥ 30g/L;
- •7.ECOG PS score 0-1;
- •Expected survival time ≥ 3 months;
- •Women: All women with potential fertility must have negative serum pregnancy test results during the screening period, and must take reliable contraceptive measures from the signing of informed consent to 3 months after the last administration;
- •Understand and sign the informed consent form.
排除标准
- •Patients with the following diseases: Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive); Interstitial lung disease/lung inflammation; Active, suspected autoimmune disease requiring systemic treatment in the past 2 years;
- •Vaccination of live attenuated vaccine within 4 weeks before enrollment, or expected to require vaccination of live attenuated vaccine during the study period;
- •Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA class III or IV);
- •Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment
- •QTcF > 480 msec at screening and > 500 msec for patients with ventricular pacemakers
- •Previous hematopoietic stem cell or bone marrow transplantation
- •7.Hypersensitivity to the study drug or its components;
- •Those who are not considered suitable to participate in the study by the investigator.
研究组 & 干预措施
Experimental: Trilaciclib+Chemotherpy+Tislelizumab
Participants received Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive trilaciclib with tislelizumab for every 3 weeks
干预措施: Tislelizumab (Drug)
Experimental: Trilaciclib+Chemotherpy+Tislelizumab
Participants received Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive trilaciclib with tislelizumab for every 3 weeks
干预措施: Trilaciclib (Drug)
Experimental: Trilaciclib+Chemotherpy+Tislelizumab
Participants received Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive trilaciclib with tislelizumab for every 3 weeks
干预措施: Carboplatin (Drug)
Experimental: Trilaciclib+Chemotherpy+Tislelizumab
Participants received Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive trilaciclib with tislelizumab for every 3 weeks
干预措施: Paclitaxel (Drug)
Active Comparator: Chemotherpy+Tislelizumab
Participants received Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive tislelizumab for every 3 weeks until PD
干预措施: Carboplatin (Drug)
Active Comparator: Chemotherpy+Tislelizumab
Participants received Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive tislelizumab for every 3 weeks until PD
干预措施: Paclitaxel (Drug)
Active Comparator: Chemotherpy+Tislelizumab
Participants received Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive tislelizumab for every 3 weeks until PD
干预措施: Tislelizumab (Drug)
结局指标
主要结局
incidence of grade ≥3 Neutrophil count decreased
时间窗: Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
The " incidence " is defined as the proportion of subjects from randomization to 15 days after the end of first-line chemotherapy treatment in which the events occurred. The occurrence of Grade 3 Neutrophil count decreased was a binary variable. If a patient had at least 1 absolute neutrophil count value \<1 × 10\^9/L during the Induction Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
次要结局
- Progress free survival (PFS)(untill Progressive Disease(PD) or death(up to 24 months))
- 1. incidence of other indicators of Myelosuppression(Grade 4 Neutrophil count decreased, grade 3 or 4 thrombocytopenia, grade 3 or 4 anemia, febrile neutropenia)(Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator)
- Usage rate of Supportive Intervention(Granulocyte colony-stimulating factor (G-CSF), platelet transfusion, red blood cell transfusion (week 5 and later), erythropoietin (ESA), iron, recombinant human interleukin-11, and/or thrombopoietin (TPO))(Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator)
- Overall Survival (OS)(From randomization until death (up to 24 months))
- Objective Response Rate (ORR)(each 42 days up to intolerance the toxicity or PD (up to 24 months))
- Disease Control Rate (DCR)(each 42 days up to intolerance the toxicity or PD (up to 24 months))
- Duration of Response (DOR)(Up to approximately 24 months)
研究者
Yongsheng Wang
Principal Investigator
Sichuan University