A Randomized, Controlled Phase II Clinical Study on the Efficacy and Safety of First-line Treatment for Extensive-stage Small Cell Lung Cancer Using a Combination Therapy of Trilaciclib, Envafolimab, Etoposide, and Carboplatin
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- The incidence of grade ≥ 3 neutropenia during chemotherapy treatment
研究概览
简要总结
This prospective, randomized, controlled phase II study aims to evaluate the efficacy of combination therapy with Envafolimab and chemotherapy in first-line extensive stage SCLC, as well as the impact of Trilaciclib on the incidence of myelosuppression and anti-tumor effects in 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years, regardless of gender;
- •Small cell lung cancer (SCLC) confirmed by histology or cytology;
- •Extensive-stage small cell lung cancer, classified as stage IV (any T, any N, M1a/b/c) according to the 8th edition of the AJCC, or T3-4 due to multiple pulmonary nodules or tumor/nodule volume too large to be included in a tolerable radiotherapy plan;
- •At least one measurable lesion on imaging（RECIST 1.1）;
- •Have not received any systemic anti-tumor treatment for extensive-stage diseases in the past. For patients who have received adjuvant/neoadjuvant chemotherapy in the past, or have received curative radiotherapy and chemotherapy for advanced diseases, if there is a gap of at least 6 months between disease progression or recurrence and the end of the last chemotherapy drug treatment, they are eligible to be included in this study;
- •Patients with asymptomatic brain metastases or brain metastases whose symptoms have stabilized after treatment;
- •Subjects are allowed to receive palliative radiation therapy (including cranial radiation therapy for symptomatic brain metastases), but the radiation therapy must be completed at least one week before enrollment;
- •The laboratory test results meet the following criteria: Hemoglobin ≥ 90 g/L, neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 100 × 10^9/L; Creatinine clearance rate (CrCl) ≥ 60 mL/min (as calculated using the Cockcroft-Gault formula); Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN or ≤ 5 × ULN (for patients with liver metastases); albumin ≥ 30 g/L; International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; Thyroid stimulating hormone (TSH) is within the normal range. If the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; The myocardial enzyme profile is within the normal range (simple laboratory abnormalities that are deemed clinically insignificant by the researchers are also allowed to be included).;
- •ECOG PS score 0 or 1;
- •Expected survival time ≥ 3 months;
- •For Female Participants: All Female Participants with potential fertility must have a negative serum pregnancy test result during the screening period, and must take reliable contraceptive measures from signing the informed consent form until 3 months after the last dose;
- •Understand and sign the informed consent form.
排除标准
- •Diagnosed with malignant diseases other than SCLC within 5 years prior to the first administration (excluding curative basal cell carcinoma, squamous cell carcinoma, and/or excised carcinoma in situ);
- •Mixed SCLC and NSCLC confirmed by histology or cytology;
- •Currently participating in interventional clinical research treatment, or having received other investigational drugs or used investigational devices within 4 weeks prior to the first administration;
- •Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that stimulate or synergistically inhibit T cell receptors (such as CTLA-4, OX-40, CD137);
- •Within 2 weeks before the first administration, the individual has received systematic systemic treatment with traditional Chinese patent medicines and simple preparations with anti lung cancer indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin, except for local use to control pleural effusion and pleural effusion);
- •Within 2 years prior to the first administration, the individual has been an active autoimmune disease requiring systemic treatment (such as the use of disease relieving drugs, corticosteroids, or immunosuppressants). Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatments;
- •Within 7 days prior to the first administration of the study, the individual was receiving systemic corticosteroid therapy (excluding topical corticosteroids via nasal spray, inhalation, or other routes) or any other form of immunosuppressive therapy; Note: Physiological doses of glucocorticoids (≤ 10 mg/day of prednisone or equivalent) are allowed to be used;
- •Individuals who are known to be allergic to the active ingredients or excipients of the investigational drugs, such as trilaciclib, envafolimab, etoposide, carboplatin, etc;
- •Patients with clinically uncontrollable pleural/peritoneal effusion (those who do not require drainage or have no significant increase in effusion after stopping drainage for 3 days can be enrolled);
- •Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive) or untreated active HBV, HCV;
- •Pregnant or lactating female participants;
- •Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA class III or IV)
研究组 & 干预措施
Trilaciclib+Envafolimab+Chemotherapy Group（TEC Group）
TEC Group received received treatment with Envafolimab in combination with Etoposide and Carboplatin for 6 cycles. Prior to each chemotherapy cycle, they were given Trilaciclib before each chemotherapy session. After 6 cycles, they were treated with Trilaciclib in combination with Envafolimab as maintenance therapy until disease progression, intolerable adverse reactions, or withdrawal of informed consent by the patient occurred, with a maximum duration not exceeding 2 years.
干预措施: Chemotherapy （Etoposide and Carboplatin） (Drug)
Trilaciclib+Envafolimab+Chemotherapy Group（TEC Group）
TEC Group received received treatment with Envafolimab in combination with Etoposide and Carboplatin for 6 cycles. Prior to each chemotherapy cycle, they were given Trilaciclib before each chemotherapy session. After 6 cycles, they were treated with Trilaciclib in combination with Envafolimab as maintenance therapy until disease progression, intolerable adverse reactions, or withdrawal of informed consent by the patient occurred, with a maximum duration not exceeding 2 years.
干预措施: Immunotherapy （Envafolimab） (Drug)
Trilaciclib+Envafolimab+Chemotherapy Group（TEC Group）
TEC Group received received treatment with Envafolimab in combination with Etoposide and Carboplatin for 6 cycles. Prior to each chemotherapy cycle, they were given Trilaciclib before each chemotherapy session. After 6 cycles, they were treated with Trilaciclib in combination with Envafolimab as maintenance therapy until disease progression, intolerable adverse reactions, or withdrawal of informed consent by the patient occurred, with a maximum duration not exceeding 2 years.
干预措施: Trilaciclib (Drug)
Envafolimab+Chemotherapy Group（EC Group）
EC Group received received treatment with Envafolimab in combination with Etoposide and Carboplatin for 6 cycles. After 6 cycles, they were treated with Envafolimab as maintenance therapy until disease progression, intolerable adverse reactions, or withdrawal of informed consent by the patient occurred, with a maximum duration not exceeding 2 years.
干预措施: Chemotherapy （Etoposide and Carboplatin） (Drug)
Envafolimab+Chemotherapy Group（EC Group）
EC Group received received treatment with Envafolimab in combination with Etoposide and Carboplatin for 6 cycles. After 6 cycles, they were treated with Envafolimab as maintenance therapy until disease progression, intolerable adverse reactions, or withdrawal of informed consent by the patient occurred, with a maximum duration not exceeding 2 years.
干预措施: Immunotherapy （Envafolimab） (Drug)
结局指标
主要结局
The incidence of grade ≥ 3 neutropenia during chemotherapy treatment
时间窗: From enrollment to the end of Cycle 6 (each cycle is 21 days)
According to CTCAE5.0
次要结局
- The incidence of ≥ grade 3 thrombocytopenia or anemia during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The duration of severe neutropenia in the first treatment cycle(From enrollment to the end of Cycle 1 (each cycle is 21 days))
- The incidence of febrile neutropenia during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The usage rate of granulocyte colony-stimulating factor (PEG-G-CSF/G-CSF) during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- Disease burden of patients during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The usage rate of erythropoietin (ESA) during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The usage rate of recombinant human interleukin-11 during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The usage rate of thrombopoietin (TPO) during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The usage rate of iron supplement during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The incidence of platelet transfusion during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- The incidence of red blood cell transfusion during chemotherapy(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- ORR(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- DCR(From enrollment to the end of Cycle 6 (each cycle is 21 days))
- DOR(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- PFS(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- OS(From date of randomization until the date of death from any cause, assessed up to 60 months)
研究者
Hua Zhong
Zhong Dr., MD
Shanghai Chest Hospital