D-BACE in Combination With Chemotherapy and Carelizumab for Resectable II-IIIA or Potentially Resectable T3-4N2 Stage IIIB NSCLC
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Evaluation of the pCR of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab
研究概览
简要总结
This study is a single-arm prospective single-center phase II study. Subjects are untreated resectable II-IIIIA or potentially resectable T3-4N2 stage IIIB NSCLC. 70 subjects will be enrolled in this prospective observation aimed at evaluating the clinical efficacy and safety of D-BACE in combination with neoadjuvant chemotherapy and carelizumab in patients with resectable II-IIIIA or potentially resectable T3-4N2 stage IIIB NSCLC. The treatment group regimen will be 3 cycles of D-BACE (DCB-loaded microspheres loaded with epirubicin 50 mg) in combination with chemotherapy and carelizumab (the specific regimen of chemotherapy will be determined by the investigator, and platinum-containing two-agent chemotherapy will generally be used). Adverse events will be monitored throughout the trial and graded for severity according to NCI CTCAE version 5.0. Tissue and blood specimens will be dynamically collected during the course of treatment for translational research.
详细描述
This study was a single-arm prospective single-center phase II study. Seventy patients with untreated resectable II-IIIA or potentially resectable T3-4N2 IIIB NSCLC will be included in this prospective study. The aim of this study is to evaluate the clinical efficacy and safety of D-BACE combined with neoadjuvant chemotherapy and camrelizumab in patients with resectable stage II-IIIA or potentially resectable T3-4N2 IIIB NSCLC. The treatment regimen was three cycles of D-BACE (epirubicin 50mg loaded on DCB microspheres) combined with chemotherapy and camrelizumab (the specific chemotherapy regimen was determined by the investigator, and generally platinum-based doubuse chemotherapy was used). Adverse events will be monitored throughout the trial and their severity will be graded according to the NCI CTCAE, version 5.0. At the same time, tissue and blood samples were dynamically collected during the treatment for related translational research exploration.
Patients could discontinue the regimen if:
Having comorbidities that significantly affect the assessment of clinical status or require discontinuation of protocol treatment (investigator's discretion); Unacceptable treatment toxicity; Disease recurrence or new primary invasive malignancy; At patient's request 4.1 Screening Subjects will complete whole-body PET-CT and contrast-enhanced brain MR Before enrollment to determine stage II-IIIB NSCLC. Patients were required to obtain adequate tissue or cell pathological diagnosis, relevant immunohistochemistry, PD-L1 protein immunohistochemistry and NGS testing before enrollment. At the same time, peripheral blood samples were collected before treatment for related indicators.
Tumor tissue was provided in newly obtained formalin-fixed specimens, preferably, or in old formalin-fixed paraffin-embedded specimens from sites not irradiated prior to biopsy. Tumor tissue must be archived (tissue blocks) before treatment. Slides ≤6 months old or recently fresh tumor biopsy slides submitted to the local study center),PD-L1 status determined:
PD-L1 positivity was defined as 1% tumor cell membrane staining positive in at least 100 evaluable tumor cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Only patients who met all the following criteria were eligible for inclusion in the study:
- •Provide written informed consent Male or female, aged 18-75 years Eastern Cooperative Oncology Group performance status ≤1 Measurable lesions in accordance with RECIST, version 1.1 Subjects must be able to provide a specimen containing tumor tissue or have a biopsy sample of newly resected tumor tissue available PD-L1 IHC testing was performed at a central laboratory during the screening phase
- •Before treatment, formalin-fixed, paraffin-embedded (FFPE) tissue blocks or non-stained tumor tissue sections and relevant pathology reports must be submitted for biomarker assessment. Tumor-tissue specimens could be fresh or archived within 6 months before enrollment.
- •The tissue must be core needle biopsy section, excisional biopsy section or open biopsy section;
- •It is recommended that fresh paraffin sections (PD-L1 assays be performed within 7 days of sectioning) slides be stored and transported in the dark
- •It is recommended that fresh tissue be fixed in 10% neutral buffered formalin for 24 to 48 hours The patient's lung function or other organ function was evaluated by the surgeon to tolerate local surgical treatment.
- •Adequate organ function assessment and laboratory screening should be performed within 7 days of initiation of therapy
- •Reproductive status:
- •A negative pregnancy test (serum or urine) in a woman of childbearing age within 72 hours before the start of treatment
- •women were non-lactating
- •For female patients, appropriate contraception should be used during treatment and for 6 months after the last dose of treatment (i.e., the time required for the 30-day ovulation cycle + the 5 half-lives of the drug).
- •Male subjects must agree to use appropriate contraception during treatment and for 7 months after the last dose of treatment (i.e., the duration of 90-day sperm turnover + 5 half-lives of the drug).
- •And male subjects had to be willing to avoid donating sperm during this period.
排除标准
- •Medical conditions Stage I, IIIB/IIIC (N3), and stage IV NSCLC patients with previous ICIs immunotherapy, targeted therapy, chemotherapy, and other systemic antitumor therapies were excluded.
- •Patients with allergy to contrast media were not eligible. Patients were excluded if their tumors had targeted alterations in EGFR and/or ALK or were known to have targeted alterations in ROS1, BRAF, HER-2, NTRK, MET, or RET. K-RAS mutations could be enrolled.
- •Active known or suspected autoimmune disease Participants were eligible if they had type I diabetes, hypothyroidism requiring only hormone-replacement therapy, skin conditions (e.g., vitiligo, psoriasis, or alopecia) that did not require systemic treatment, or other conditions that were not expected to recist in the absence of an external trigger.
- •Patients with active hepatitis B (positive hepatitis B surface antigen HBsAg test) or hepatitis C (positive HCV RNA test) Patients with previous HBV infection or a decommissioned HBV infection (defined as positive for the hepatitis B core antibody HBcAb and negative for HBsAg) were eligible to participate. Patients were required to provide HBV DNA test results before enrollment, and participants who were HBV carriers or required antiviral therapy were not eligible. Patients who tested positive for HCV antibodies could participate in the study only if they had negative PCR results for HCV RNA.
- •Any history of arterial thrombosis within 6 months of human immunodeficiency virus (HIV) -positive or acquired immunodeficiency syndrome (AIDS), History of deep vein thrombosis, pulmonary embolism, or any other major thromboembolism within 3 months uncontrolled angina, arrhythmia, or congestive heart failure within 5 years other active malignancy (except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer, superficial bladder cancer, or prostate cancer, breast cancer in situ) Patients with contraindications to local treatment (including surgery or intervention) as judged by the investigator.
- •Serious or uncontrolled medical illness The patient has psychosis or other medical conditions that result in treatment nonadherence History of severe hypersensitivity reactions to other monoclonal antibodies Patients who are unwilling to sign informed consent forms Patients who do not want follow-up Physical and laboratory tests Laboratory screening values must exclude the following criteria (CTCAE version 5 applies)
- •Bone marrow function:
- •White blood cell count < 2000/uL, neutrophil < 1500/uL, platelet < 100×103/Ul, hemoglobin < 9.0g/dL
- •Liver function:
- •Serum total bilirubin > 1.5 times the upper limit of normal value (ULN);
- •In the case of liver metastases, AST and ALT were > 5×ULN and total bilirubin > 1.5ULN
- •Coagulation function:
- •Abnormal coagulation function was defined as international normalized ratio (INR) or prothrombin time (PT) > 1.5 times ULN; If the subject was receiving anticoagulant therapy, PT was outside the intended use of anticoagulant drugs.
- •Renal function:
- •Urinary protein > 2+, or 24-hour urinary protein ≥1g; Serum creatinine > 1.5×ULN or calculated creatinine clearance (CrCl) < 50ml/min (using Cockcroft-Gault formula) Female CrCL=([140-age] × weight (kg) ×0.85)/(72× serum creatinine (mg/dL) Male CrCL=([140-age] × weight (kg) ×1.00)/(72× serum creatinine (mg/dL) Allergy and adverse drug reactions 1) A history of hypersensitivity to other monoclonal antibodies 2) A history of allergic or hypersensitive reactions to the components of the study drug Other exclusion criteria
- •Prisoners or subjects under compulsory confinement.
- •subjects who have been involuntarily detained for treatment of mental or physical illness (e.g., infectious disease).
- •Careful consideration has been given to the eligibility criteria for this study to ensure the safety of the study subjects and to ensure the availability of the study results.
研究组 & 干预措施
D-BACE in combination with chemotherapy and karelizumab
3 cycles of D-BACE (DCB-loaded microspheres loaded with epirubicin 50 mg) in combination with chemotherapy and karelizumab (the specific regimen of chemotherapy is determined by the investigator, and platinum-containing two-agent chemotherapy is generally used).
干预措施: D-BACE in combination with chemotherapy and karelizumab (Combination Product)
结局指标
主要结局
Evaluation of the pCR of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab
时间窗: From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day)
Evaluation of the pathological complete response (pCR) of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab
次要结局
- Evaluation of the MPR of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab(From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day))
- Evaluation of the ORR of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab(From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day))
- Evaluation of the EFS of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab(From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day))
- Evaluation of the PFS of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab(From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day))
- Evaluation as assessed by CTCAE v4.0 of the safety and tolerability of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab(From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day))
- Evaluation of the OS of resectable II-IIIA or potentially resectable T3-4N2 stage IIIB NSCLC treated with D-BACE in combination with chemotherapy and karelizumab(From enrollment to the end of treatment at 3 cycle (1 cycle is 21 day))