Clinical Study on the Prevention of Driver Gene Negative Ib-IIIb Lung Cancer Recurrence and Metastasis by Staged Chinese Herbal Medicine Combined With Chemotherapy and Immune Checkpoint Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 367
- 试验地点
- 1
- 主要终点
- Disease-free Survival(DFS)
研究概览
简要总结
This project adopts a prospective, multicenter, randomized controlled clinical study to investigate the treatment of TCM in postoperative patients with driver gene negative lung cancer, according to two phases of postoperative adjuvant therapy: (i) chemotherapy phase immunotherapy phase. In this study, 367 patients (183 in the control group and 184 in the trial group) will be observed over 4 years, and the quality of life, toxic effects and safety of this therapy will be investigated. This study will provide evidence-based evidence for the establishment and optimization of a new model of postoperative staged TCM with adjuvant chemo-immunotherapy for lung cancer.
详细描述
With the discovery of lung cancer driver genes, postoperative adjuvant therapy for lung cancers has been revolutionized. ADJUVANT, EVAN, EVIDNECE and IMPACT, have successively conducted efficacy and safety studies in the field of postoperative adjuvant therapy after generation EGFR-TKI. Adjuvant targeted therapy is also recommended by guidelines based on the significant improvement of DFS in mutation-positive patients. Unfortunately, 55% of NSCLC patients are driver gene-negative. Research in postoperative mutation-negative patients is relatively lagging behind. Chemotherapy remains the treatment of choice at this time. How to delay recurrence of metastasis in this population needs further study. Studies have shown that 1 year of adjuvant atezolizumab after chemotherapy in postoperative driver gene-negative patients significantly prolongs median DFS. For any PD-L1-expressing stage II-IIIa patients, adjuvant atezolizumab therapy has a median DFS of 42.3 months. Atezolizumab is recommended in the NCCN 2021 edition of clinical guidelines for patients with stage IIb-IIIa TPS ≥ 1%. In recent years, there has been great progress in the study of combined adjuvant therapy of Chinese medicine after lung cancer surgery. At present, research on TCM in the field of postoperative lung cancer is mainly focused on combined chemotherapy, which can reduce the occurrence of adverse events, improve quality of life, prevent recurrence and metastasis, and increase survival rate. More and higher-grade clinical evidence is needed to explore and validate the combination of TCM with immunotherapy.
Using a multicenter, randomized, double-blind, controlled prospective study, 367 patients with stage Ib-IIIb driver gene-negative NSCLC after undergoing radical surgery will be randomly divided into experimental and control groups, and postoperative adjuvant therapy will be administered in two phases: (i) chemotherapy phase: observation group (chemotherapy + TCM 1), control group (chemotherapy + TCM 1 placebo); (ii) immunization phase: observation group (ICIs + TCM2), control group (ICIs + TCM2 placebo). Treatment cycles will be 4 cycles of chemotherapy and 12 cycles of immunotherapy, and the indication for discontinuation will be the end of treatment or the patient's intolerance of treatment. Patients will be followed up regularly thereafter. The primary efficacy assessments are: disease-free survival (DFS); secondary efficacy assessments are: (1) quality of life: EORTC QLQ-LC43(V 4.0) scale; (2) changes in clinical signs of TCM; (3) biological indicators: ctDNA-MRD, peripheral blood immune factor series, plasma exosomal PD-L1; (4) overall survival (OS). An assessment of the toxic side effects and safety of the treatment regimen is also made by using CTC AE (V5.0). This regimen is expected to prolong disease-free survival and reduce toxic side effects. The study will provide evidence to optimize and promote the protocol of postoperative TCM combined with immunotherapy for lung cancer.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who underwent complete surgical resection (R0) with postoperative pathology confirmed as stage Ib to IIIb non-small cell lung cancer.
- •Patients whose tissue or blood specimens tested negative for driver genes.
- •Patients who received their first chemotherapy within 8 weeks postoperatively.
- •Age ≥ 18 years ≤ 74 years, regardless of gender.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 points.
- •absolute neutrophil value >1.5×109 /L, platelet count >80×109 /L, hemoglobin >90mg/dL; no abnormal liver and kidney function test results.
- •Understand and agree to participate in this study and sign the informed consent form.
排除标准
- •Having unresectable or metastatic disease, pathology reports without a clear pathological diagnosis, showing the presence of residual lesions at the microscopic surgical margins, and surgical residual lesions.
- •Any medical condition with a life expectancy of less than 5 years, except for risk of recurrent lung cancer.
- •Current malignant disease or history of malignant disease (except resected NSCLC), combined with serious diseases of the heart, liver, kidney and hematopoietic system, diagnosed and/or requiring treatment within the past three years.
- •With a history of psychiatric disorders that are not easily controlled.
- •Patients who are pregnant or lactating.
- •Patients who are allergic to therapeutic drugs.
研究组 & 干预措施
chemotherapy plus TCM 1 placebo&ICIs plus TCM2 placebo
Phase1： Chemotherapy：Proposed platinum-containing two-drug adjuvant chemotherapy, vincristine/paclitaxel/docetaxel/pemetrexed/gemcitabine plus cisplatin/carboplatin within 8 weeks after surgery, according to CSCO guidelines (2022).
Placebo1 granules: oral granules, which the taste and smell are similar to experimental TCM granules and has no therapeutic effect , twice a day, every 21 days for 4 cycles.
Phase 2：One of the following agents may be selected after chemotherapy：Nivolumab/Pembrolizumab/Durvalumab/Atezolizumab/ Camrelizumab/Dupilumab/Sintilimab/Tislelizumab.A total of 12 cycles will be performed or the patient will discontinue the drug due to intolerable toxic side effects.
Placebo2 granules: oral granules, which the taste and smell are similar to experimental TCM granules and has no therapeutic effect, twice a day, every 21 days for 12 cycles.
干预措施: chemotherapy plus TCM 1placebo &ICIs plus TCM2 placebo (Drug)
结局指标
主要结局
Disease-free Survival(DFS)
时间窗: 5 years
Time from patient enrollment to date of objective tumour recurrence from any cause.
次要结局
- Overall Survival(OS)(5 years)
- Molecular Residual Disease Circulating Tumor DNA(ctDNA-MRD)(5 years)
- Quality of Life Measurement Scale (EORTC QLQ-C30)(5 years)
- Quality of Life Measurement Specific Module Scale for Patients with Lung Cancer (EORTC QLQ-LC13)(5 years)
- Laboratory Indicator Evaluation Criteria(5 years)
- Circulating Exosome PD-L1(5 years)
- Safety Assessment Evaluated According to Common Toxicity Criteria(5 years)
- TCM Symptoms Changes(5 years)
研究者
Ling Xu
Chief Physician
Shanghai University of Traditional Chinese Medicine