Neoadjuvant Chemotherapy Plus Cadonilimab for Locally Advanced Cervical Cancer : a Multicentre, Single Arm, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Pathological complete response
研究概览
简要总结
Main Purpose of this study is to determine the efficacy and safety of Cadonilimab combined with chemotherapy (cisplatin) for locally advanced cervical cancer.
This is an multicentre, single Arm, Phase 2 Trial study of Cadonilimab with Cisplatin in the treatment of locally advanced cervical cancer. 29 eligible patients will receive Cadonilimab（10mg/kg, iv., D1, q3w）with Cisplatin ( 75mg/ m2, iv., D2， q3w) for a total of 2-4 cycles before radical surgical treatment.
详细描述
Detailed Description:
Study Title : Neoadjuvant Chemotherapy Plus Cadonilimab for Locally Advanced Cervical Cancer : a Multicentre, Single Arm, Phase 2，prospective Trial Main Study Objectives : Determine the efficacy and safety of Cadonilimab combined with chemotherapy (cisplatin) for locally advanced cervical cancer.
Secondary Objective: Explore the correlations between the expression of PD-L1 , Tumor Mutational Burden（TMB） levels, immune cell subsets, tumor microenvironment and therapeutic efficacy
Study Endpoints :
Primary Endpoint :Pathological complete response rate (pCR) and Radiological response rate (RS) Secondary Endpoints :Safety (Incidence and severity of adverse events (AE) caused by drug treatment and perioperative complications, clinically significant abnormal laboratory test results;Clinical downstaging rate (downstaging of T and/or N); Major pathological response rate (MPR);Disease-free survival (DFS); Objective response rate (ORR) ,Disease control rate (DCR), progression-free survival (PFS), and 5-year overall survival rate (OS) based on RECIST v1.1 and mRECIST evaluation.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, age ≥18 years;
- •Histologically confirmed cervical cancer, FIGO stage IB3, IIA2, IIB, IIIC, and assessed by the researcher as resectable;
- •No previous systemic treatment for the current disease, including surgical treatment, antitumor chemoradiotherapy/immunotherapy, etc.;
- •Patients who agree to undergo radical surgical treatment and are judged by the surgeon to have no surgical contraindications;
- •ECOG score of 0-1;
- •Expected survival time >6 months;
- •Sufficient organ function, the subject must meet the following laboratory indicators:
- •Neutrophil absolute count (ANC) ≥1.5x10^9/L ; Platelets ≥100x10^9/L ;Hemoglobin >9g/dL ; Total bilirubin ≤1.5× upper limit of normal (ULN); Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5×ULN; Serum creatinine ≤1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 ml/min; international normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN; Normal thyroid function; Myocardial enzymes within the normal range
排除标准
- •Diagnosis of other malignancies within 5 years prior to the first dose (excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has undergone radical resection).
- •Current participation in an interventional clinical study or receipt of other investigational drugs or devices within 4 weeks prior to the first dose.
- •Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or drugs targeting other stimulatory or co-inhibitory T-cell receptors .
- •Systemic treatment with Chinese herbal medicines with antitumor indications or immunomodulatory agents (e.g., thymosin, interferon, interleukin, excluding local use for pleural effusion control) within 2 weeks prior to the first dose.
- •Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, glucocorticoids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroxine, insulin, or physiologic glucocorticoids for adrenal/pituitary insufficiency) are not considered systemic treatment.
- •Systemic glucocorticoid therapy (excluding nasal sprays, inhalations, or other local routes) or any immunosuppressive therapy within 7 days prior to the first dose.
- •History of allogeneic organ transplantation (excluding corneal transplants) or allogeneic hematopoietic stem cell transplantation.
- •Known hypersensitivity to any study drug.
- •Presence of multiple factors affecting cisplatin use (e.g., platinum allergy).
- •Inadequate recovery from prior intervention-related toxicity or complications (i.e., >Grade 1 or not returned to baseline, excluding fatigue or alopecia).
- •Known history of Human Immunodeficiency Virus（ HIV） infection .
- •Untreated active hepatitis B （HBV）(defined as HBsAg-positive with HBV-DNA exceeding the upper limit of normal at the study site).
- •Active hepatitisC (HCV) infection (HCV antibody-positive with HCV-RNA above the lower detection limit).
- •Administration of live vaccines within 30 days prior to the first dose (Cycle 1, Day 1).
- •Pregnant or lactating women.
- •Severe or uncontrolled systemic diseases, including:Symptomatic resting Electrocardiograph abnormalities (e.g., complete left bundle branch block, ≥Grade II heart block, ventricular arrhythmia, atrial fibrillation).Unstable angina, congestive heart failure, or chronic heart failure ≥NYHA class II.Arterial thromboembolism, ischemia, myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to enrollment.Poorly controlled hypertension (systolic >140 mmHg, diastolic >90 mmHg).History of non-infectious pneumonitis requiring glucocorticoids within 1 year or current active interstitial lung disease.
- •Active tuberculosis.
- •Active or uncontrolled infection requiring systemic therapy.
- •Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction.
- •Liver diseases (e.g., cirrhosis, decompensated liver disease, acute/chronic active hepatitis).
- •Poorly controlled diabetes (fasting blood glucose >10 mmol/L).
- •Urine protein ≥++ on urinalysis with 24-hour urine protein >1.0 g.
- •Psychiatric disorders impairing compliance.
- •Any condition (e.g., medical history, abnormal lab/test results, concurrent treatments) that may interfere with study outcomes, participation, or pose risks, as judged by the investigator.
研究组 & 干预措施
Neoadjuvant chemotherapy plus cadonilimab for locally advanced cervical cancer
Cadonilimab 10mg/kg, ivgtt., D1, q3w with Cisplatin ( 75mg/ m2, ivgtt., D2, q3w) for a total of 2-4 cycles before radical surgical treatment.
干预措施: Cadonilimab combined with cisplatin (Drug)
结局指标
主要结局
Pathological complete response
时间窗: From enrollment to 5 years after the end of treatment
The proportion of subjects with no residual viable tumor cells and negative lymph nodes among all subjects
次要结局
未报告次要终点
研究者
Xie Ya
Professor
The First Affiliated Hospital of Zhengzhou University