|
研究疾病：
|
非小细胞肺癌
|
研究疾病代码：
|
|
|
Target disease：
|
non-small lung cancer
|
Target disease code：
|
|
研究类型：
Study type：
|
干预性研究
Interventional study
|
研究设计：
Study design：
|
随机平行对照
randomized controlled trial(parallel group design)
|
|
研究所处阶段：
Study phase：
|
探索性研究/预试验
Pilot clinical trial
|
|
研究目的：
|
1. 明确扶正抗癌方联合PD-1抑制剂治疗PD-L1表达阳性＜50%的痰湿型NSCLC的疗效；
2. 明确痰湿型非小细胞肺癌肠道菌群结构的组成、丰度变化、多样性、菌属分类、富集通路及其与PD-L1之间关系；
|
|
Objectives of Study：
|
1. To clarify the efficacy of Fuzheng Kangai formula combined with PD-1 inhibitor for non-small cell lung cancer with positive PD-L1 expression less than 50% and phlegm-dampness syndrome.
2. To clarify the composition, abundance change, diversity, bacterial classification, enrichment pathways of intestinal flora and the relationship between them and PD-L1 expression in advanced non-small cell lung cancer with phlegm-dampness syndrome.
|
|
药物成份或治疗方案详述：
|
试验组：PD-1抑制剂(200mg q3w ivd 或 200mg q2w ivd)+扶正抗癌颗粒剂（1袋 tid po）
对照组：PD-1抑制剂(200mg q3w ivd 或 200mg q2w ivd)+扶正抗癌安慰剂（1袋 tid po）
|
|
Description for medicine or protocol of treatment in detail：
|
The experimental group: PD-1 inhibitor(200mg q3w ivd or 240mg q2w ivd) + Fuzheng Kangai granule（1 bag tid po）
The control group: PD-1 inhibitor(200mg q3w ivd or 240mg q2w ivd) + placebo（1 bag tid po）
|
|
纳入标准：
|
1. 根据国际肺癌研究协会和美国癌症分类联合委员会第8版肺癌TNM分期分类，具有组织学或细胞学证实的不能手术治疗且已接受过一线治疗的转移性或复发性（IV期）NSCLC的患者,或拒绝化疗的一线患者；
2. PD-L1＜50%；
3. 中医证型为痰湿证；
4. 年龄≥18岁且小于或等于80岁；
5. 预期寿命超过3个月；
6. 研究者根据RECIST 1.1标准证实具有至少一个可测量病灶。位于既往放疗照射野内或局部治疗后的可测量病灶如果证实发生进展，则可选作靶病灶；
7. 东部肿瘤协作组（ECOG）体能状态评分为0或1；
8. 血液学功能充分，定义为中性粒细胞绝对计数≥1.5×109 /L，血小板计数≥100 ×109 /L，血红蛋白≥90g/L （7日内无输血史）；
9. 肝功能充分，定义为总胆红素水平≤1.5倍正常上限（ULN）和谷草转氨酶（AST）和谷丙转氨酶（ALT）水平≤2.5倍ULN的所有患者，或对于有肝脏转移的患者，AST和ALT水平≤5倍ULN；
10. 肾功能充分，定义为肌酐清除率≥ 60 ml/min（Cockcroft-Gault公式）；
11. 凝血功能充分，定义为国际标准化比值（INR）或凝血酶原时间（PT）≤1.5倍ULN；若受试者正在接受抗凝治疗，只要PT在抗凝药物拟定的范围内即可；
12. 对于育龄期女性受试者，应在接受首次研究药物给药之前的3天内呈尿液或血清妊娠试验阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验；
13. 自愿加入本研究，签署签署书面知情同意。
|
|
Inclusion criteria
|
1. According to the 8th TNM classification of lung cancer edited by International Association for the Study of Lung Cancer (IASLC) and American Joint Committee on Cancer(AJCC)patients are unable to accept surgical resection and already accepted first line treatment with histologically or cytologically confirmed metastatic or recurrent NSCLC (stage IV).
2. PD-L1 expression are positive and less than 50%.
3. The Chinese medicine syndrome diagnosed with phlegm-dampness syndrome.
4. Range in Age is from 18 to 80 years old.
5. Life expectancy is over 3 months.
6. The investigator confirmed the presence of at least one measurable lesion according to RECIST 1.1 criteria.
7. Eastern Cooperative Oncology Group (ECOG) performance status is 0 or 1.
8. Hematologic function was sufficient, defined as neutrophil absolute count ≥1.5×109/L, platelet count ≥100 ×109 /L, hemoglobin ≥90g/L (no history of blood transfusion within 7 days)
9. Liver function was sufficient, defined as total bilirubin levels ≤1.5 times the upper normal limit (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 times ULN in all patients, or AST and ALT levels ≤5 times ULN in patients with liver metastasis;
10. Renal function was sufficient, defined as creatinine clearance ≥ 60 mL /min (Cockcroft-Gault formula);
11. The function of blood clotting was sufficient, defined as international standardized ratio (INR) or prothrombin time (PT) ≤1.5 ULN. If the subject is receiving anticoagulant therapy, as long as PT is in the prescribed anticoagulant range, it is acceptable.
12. For female subjects of reproductive age, a negative urine or serum pregnancy test should be presented within 3 days prior to receiving the first study drug. If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is required
13. Sign written informed consent to participate in the study voluntarily.
|
|
排除标准：
|
1. 当前正在参与干预性临床研究治疗，或在首次给药前4周内接受过其他研究药物或研究器械治疗；
2. 既往接受过下列疗法：抗PD-1、抗PD-L1或抗PD-L2药物或者针对另一种刺激或协同抑制T细胞受体（例如，CTLA-4、OX-40、CD137）的药物；
3. 给药前3周内接受过重大手术治疗；
4. 存在需临床干预的活动性咯血、活动性憩室炎、腹腔脓肿、胃肠道梗阻和腹膜转移；
5. 接受过实体脏器或血液系统移植；
6. 存在临床上不可控制的胸腔积液/腹腔积液（不需要引流积液或停止引流3天积液无明显增加的患者可以入组）；
7. 肿瘤压迫周围重要脏器（如食管）且伴随相关症状；
8. III-IV级充血性心力衰竭（纽约心脏病协会分级），控制不佳且有临床意义的心律失常；
9. 合并严重感染需进行抗生素治疗；
10. 已知对PD-1抑制剂活性成分和或任何辅料有过敏反应；
11. 首次给药前2年内发生过需要全身性治疗（例如使用病情改善药物、皮质类固醇或免疫抑制剂）的活动性自身性免疫疾病。
12. 需要长期全身性使用皮质类固醇的患者。由于COPD、哮喘需要间断使用支气管扩张药、吸入性皮质类固醇，或局部注射皮质类固醇的患者可以入组。
13. 有症状的中枢神经转移。
|
|
Exclusion criteria：
|
1. Currently participating in an interventional clinical study or receiving another study drug or study device within 4 weeks prior to initial dosing.
2. Prior treatment: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulating or co-inhibiting T-cell receptor (e.g., CTLA-4, OX-40, CD137).
3. Major surgery was performed within 3 weeks prior to administration.
4. There are active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal obstruction, and peritoneal metastasis requiring clinical intervention.
5. A solid organ or blood system transplant has been received.
6. There is clinically uncontrollable pleural effusion or abdominal effusion (patients who do not need drainage effusion or who stop drainage for 3 days without significant increase in effusion can be included in the group).
7. The tumor compresses important surrounding organs such as the esophagus with associated symptoms.
8. Grade III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmia.
9. Severe infection should be treated with antibiotics.
10. Known allergic reactions to the active ingredients of pD-1 inhibitors and or to any excipients.
11. An active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressants) developed within 2 years prior to initial administration.
12. Patients requiring long-term systemic corticosteroid use. Patients requiring intermittent use of bronchodilators, inhaled corticosteroids, or topical corticosteroids for COPD or asthma may be enrolled.
13. Symptomatic central nervous system metastases.
|
|
研究实施时间：
Study execute time：
|
从From
2021-07-01
至To
2026-07-31
|
征募观察对象时间：
Recruiting time：
|
从From
2022-01-06
至To
2026-07-25
|
