A Multicentre, Prospective, Randomized, Double-blind, Placebo-controlled Study of Nimotuzumab Plus Concurrent Chemoradiotherapy Sequential Maintenance Treatment for Locally Advanced Cervical Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 460
- 主要终点
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of nimotuzumab plus concurrent chemoradiotherapy sequential maintenance therapy versus placebo combined with concurrent chemoradiotherapy in patients with locally advanced cervical squamous cell carcinoma.
The primary hypotheses are that nimotuzumab plus concurrent chemoradiotherapy sequential maintenance therapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival.
详细描述
This is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical study.The trail will enroll 460 subjects (FIGO 2018, stageIB3-IVA)who meet enrollment criteria but do not meet exclusion criteria. According to clinical stage (FIGO 2018 stage, stage IB3-IIB or III-IVA) 、tumor diameter (>4cm or ≤4cm)、 age (≥18 years and < 65 years old or ≥65 years old and ≤80 years old) for stratified randomization. They are divided into experimental group and control group according to 1:1. Patients in the experimental group will receive nimotuzumab 400mg on the basis of concurrent chemoradiotherapy, once a week for 7-8 weeks, and then maintenance treatment once every 2 weeks for 24 weeks. Using placebo(Nimotuzumab injection mimics) in the control group 80 ml on the basis of concurrent chemoradiotherapy, once a week for 7 to 8 weeks, after the maintenance treatment, once every 2 weeks for 24 weeks. Patients with incomplete tumor response assessed by imaging and pathological examination 3 months after radiotherapy can be given 2-4 cycles of adjuvant chemotherapy with cisplatin/carboplatin combined with paclitaxel regimen. Regular imaging examination and survival follow-up were performed after treatment. The primary efficacy end point was progression-free survival.
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
- Double (Participant, Investigator)
盲法说明
This study is double-blind and will blind both the investigator and the subjects. All participants in the study (including data managers and biostatisticians) will be unaware of treatment assignment (except blind statisticians).
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •1.Aged 18-80 years old;
- •2.Histologically diagnosed primary cervical squamous cell carcinoma, with clinical stage IB3-IVA (FIGO 2018);
- •3.At least one measurable lesion according to RECIST 1.1;
- •4.Absence of severe hematopoietic dysfunction and heart, lung, liver, kidney dysfunction and immunodeficiency, laboratory test results meet the following criteria: Hemoglobin ≥ 90 g/L; Absolute neutrophil count ≥ 1.5 × 10^9/L and white blood cell count ≥ 3.0 × 10^9/L; Platelet count ≥ 100 × 10^9/L; Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN ; Total bilirubin ≤ 1.5 × ULN; Serum creatinine ≤ 1.0 × ULN;
- •5.ECOG score 0-1 points;
- •6.Women of childbearing potential must have a negative serum or urine HCG within 72 hours prior to enrollment (postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. A pregnancy test is not required for women who have demonstrated tubal ligation); Women of childbearing potential who are willing to take medically recognized contraceptive measures during the trial;
- •7.Compliance is good and informed consent is voluntarily signed.
排除标准
- •1.Cervical adenocarcinoma and rare pathological types of malignant tumors;
- •2.Previous surgery for cervical cancer, pelvic radiation therapy, systemic chemotherapy, tumor targeted therapy, immunotherapy;
- •3.Ureteral obstruction, inability to place ureteral stent or pyelostomy;
- •4.Pregnant or lactating women;
- •5.Patients with rectovaginal fistula/vaginovesical fistula/uncontrolled vaginal bleeding or at risk of fistula;
- •6.Had undergone major surgery (except biopsy) within 4 weeks prior to randomization;
- •7.Had received a live vaccine within 4 weeks prior to the initial study drug treatment or planned to vaccinate during the study;
- •8.Human immunodeficiency virus (HIV) infection;Active hepatitis B (the quantitative detection result of HBV DNA exceeds the lower limit of detection), or HCV infection (the quantitative detection result of HCV RNA exceeds the lower limit of detection);
- •9.Had the following serious medical conditions: a) Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg), or had experienced a hypertensive crisis; b) Myocardial infarction and unstable angina occurred within 6 months before randomization; c) Decompensated heart failure within three months before enrollment (NYHA class III and IV); d) The presence of severe arrhythmias requiring long-term medical intervention, except in patients with asymptomatic atrial fibrillation with stable ventricular rate; e) Left ventricular ejection fraction (LVEF)<50%; f) The presence of uncontrolled hyperglycemia; g) The presence of uncontrollable infections；
- •10.The presence of active or suspected autoimmune diseases, except for type 1 diabetes、hypothyroidism or skin conditions that do not require systemic treatment (vitiligo、psoriasis or alopecia)；
- •11.Conditions requiring systemic treatment with corticosteroids or other immunosuppressive agents within 14 days before randomization；
- •12.Patients with a history of other malignant tumors (except cured cutaneous basal cell carcinoma);
- •13.Patients with Crohn's disease and ulcerative colitis;
- •14.Patients who are participating in other clinical trials or have stopped clinical trials for less than 4 weeks;
- •15.Patients with known hypersensitivity to Nimotuzumab or its components;
- •16.Patients with contraindications to cisplatin、carboplatin and paclitaxel;
- •17.Patients with neurological or psychiatric disorders affecting cognitive ability;
- •18.Patients whose lesions cannot be treated with intracavitary radiotherapy as assessed by the investigator;
- •19.Any condition that, in the opinion of the Investigator, may be inappropriate for patients in the study.
研究组 & 干预措施
Nimotuzumab+chemoradiotherapy
Participants receive Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by Nimotuzumab 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of Nimotuzumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: Nimotuzumab (Biological)
Nimotuzumab+chemoradiotherapy
Participants receive Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by Nimotuzumab 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of Nimotuzumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: Cisplatin (Drug)
Nimotuzumab+chemoradiotherapy
Participants receive Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by Nimotuzumab 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of Nimotuzumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: External Beam Radiotherapy (EBRT) (Radiation)
Nimotuzumab+chemoradiotherapy
Participants receive Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by Nimotuzumab 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of Nimotuzumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: Brachytherapy (Radiation)
placebo for Nimotuzumab+chemoradiotherapy
Participants receive placebo for Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by placebo 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: Cisplatin (Drug)
placebo for Nimotuzumab+chemoradiotherapy
Participants receive placebo for Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by placebo 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: External Beam Radiotherapy (EBRT) (Radiation)
placebo for Nimotuzumab+chemoradiotherapy
Participants receive placebo for Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by placebo 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: Brachytherapy (Radiation)
placebo for Nimotuzumab+chemoradiotherapy
Participants receive placebo for Nimotuzumab 400 mg intravenously (IV) on Day 1 of each week cycle (QW) for 7-8 cycles followed by placebo 400 mg IV on Day 1 of each 2-week cycle (Q2W) for an additional 12 cycles. During the QW dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once or divides into 3 times per week (QW) for 4 or 5 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80-85 Gray Units (Gy) for volume-directed given with the total duration of radiation treatment not to exceed 8 weeks .
干预措施: placebo for Nimotuzumab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed Blinded Independent Central Review (BICR)
时间窗: Up to approximately 5 years
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
次要结局
- 3-,5-Year Locoregional Recurrence-Free Survival(LRRFS)(Up to approximately 3 and 5 years)
- Incidence of Treatment-Emergent Adverse Events(Within 30 days from the start of treatment to the end of the last treatment)
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by by the Investigator(Up to approximately 5 years)
- 3-,5-Year Disease Free Survival(DFS)(Up to approximately 3 and 5 years)
- 3-,5-Year Distant Metastasis-free Survival (DMFS)(Up to approximately 3 and 5 years)
- Tumor Regression Rate(TRR)(From date of randomization until the date of brachytherapy,assessed up to 5 weeks)
- Complete Response Rate(3 months later after treatment)
- Objective Response Rate(3 months later after treatment)
- 3-,5-Year Overall Survival (OS)(Up to approximately 3 and 5 years)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score(Baseline and up to approximately 5 years)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Score(Baseline and up to approximately 5 years)