A Study of Nimotuzumab Plus Concurrent Chemoradiotherapy Sequential Maintenance Treatment for Cervical Carcinoma

NCT ID: NCT06333821

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 460 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2030-04-01

Brief Summary

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.

Detailed Description

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.

Conditions

Cervical Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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 .

Group Type: EXPERIMENTAL

Nimotuzumab

Intervention Type: BIOLOGICAL

Nimotuzumab 400mg

Cisplatin

Intervention Type: DRUG

Cisplatin 40mg/m\^2

External Beam Radiotherapy (EBRT)

Intervention Type: RADIATION

External Beam Radiotherapy (EBRT)

Brachytherapy

Intervention Type: RADIATION

Brachytherapy

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 .

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Cisplatin 40mg/m\^2

External Beam Radiotherapy (EBRT)

Intervention Type: RADIATION

External Beam Radiotherapy (EBRT)

Brachytherapy

Intervention Type: RADIATION

Brachytherapy

placebo for Nimotuzumab

Intervention Type: DRUG

placebo for Nimotuzumab 400mg

Interventions

Nimotuzumab

Nimotuzumab 400mg

Intervention Type: BIOLOGICAL

Cisplatin

Cisplatin 40mg/m\^2

Intervention Type: DRUG

External Beam Radiotherapy (EBRT)

External Beam Radiotherapy (EBRT)

Intervention Type: RADIATION

Brachytherapy

Brachytherapy

Intervention Type: RADIATION

placebo for Nimotuzumab

placebo for Nimotuzumab 400mg

Intervention Type: DRUG

Other Intervention Names

placebo

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Biotech Pharmaceutical Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Junjie Wang

Role: STUDY_CHAIR

Peking University Third Hospital

Lichun Wei

Role: STUDY_CHAIR

TThe First Affiliated Hospital，the Air Force Medical University

Lijuan Zou

Role: STUDY_CHAIR

The Second Affiliated Hospital of Dalian Medical University

Zi Liu

Role: STUDY_CHAIR

First Affiliated Hospital Xi'an Jiaotong University

Jiayi Chen

Role: STUDY_CHAIR

Ruijin Hospital

Huijun Cheng

Role: STUDY_CHAIR

Henan Cancer Hospital

Rutie Yin

Role: STUDY_CHAIR

West China Second University Hospital

Xiangkun Yuan

Role: STUDY_CHAIR

Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine.HeBei

Hui Qiu

Role: STUDY_CHAIR

Zhongnan Hospital

Hong Zhu

Role: STUDY_CHAIR

Xiangya Hospital of Central South University

Tiejun Wang

Role: STUDY_CHAIR

Second Hospital of Jilin University

Xiaomei Fan

Role: STUDY_CHAIR

The Fourth Hospital of Hebei Medical University Hebei Tumor Hospital

Keqiang Zhang

Role: STUDY_CHAIR

Hunan Cancer Hospital

Dihong Tang

Role: STUDY_CHAIR

Hunan Cancer Hospital

Qiongyu Lan

Role: STUDY_CHAIR

Second Affiliated Hospital of Nanchang University

Xiaoying Xue

Role: STUDY_CHAIR

The Second Hospital of Hebei Medical University

Song Gao

Role: STUDY_CHAIR

Shengjing Hospital

Guang Li

Role: STUDY_CHAIR

First Hospital of China Medical University

Qiuhong Tian

Role: STUDY_CHAIR

The First Affiliated Hospital of Nanchang University

Guoqing Wang

Role: STUDY_CHAIR

Shaanxi Provincial Cancer Hospital

Dong Qian

Role: STUDY_CHAIR

The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

Manbo Cai

Role: STUDY_CHAIR

The First Affiliated Hospital of University of South China

Yuhua Gao

Role: STUDY_CHAIR

Liaoning Cancer Hospital & Institute

Dehua Wu

Role: STUDY_CHAIR

Nanfang Hospital, Southern Medical University

Xiaoge Sun

Role: STUDY_CHAIR

The Affiliated Hospital of Inner Mongolia Medical University

Yunyan Zhang

Role: STUDY_CHAIR

Cancer Hospital Affiliated to Harbin Medical University

Kun Gao

Role: STUDY_CHAIR

Guangxi Medical University Cancer Center

Qin Lin

Role: STUDY_CHAIR

The First Affiliated Hospital of Xiamen University

Qin Xu

Role: STUDY_CHAIR

Fujian Cancer Hospital

Hao Yang

Role: STUDY_CHAIR

Peking University Cancer Hospital Inner Mongolia Hospital

Rong Huang

Role: STUDY_CHAIR

First People's Hospital of Foshan

Xianming Li

Role: STUDY_CHAIR

Shenzhen People's Hospital

Juntao Ran

Role: STUDY_CHAIR

LanZhou University

Xiaojie Ma

Role: STUDY_CHAIR

Affiliated Hospital of North Sichuan Medical College

Xingrao Wu

Role: STUDY_CHAIR

Yunnan Cancer Hospital

Yipeng Song

Role: STUDY_CHAIR

Yantai Yuhuangding Hospital

Jun Wang

Role: STUDY_CHAIR

Tianjin Cancer Hospital Airport Hospital

Dapeng Li

Role: STUDY_CHAIR

Shandong Cancer Hospital ＆ Institute

Siyuan Zeng

Role: STUDY_CHAIR

Jiangxi Maternal and Child Health Hospital

Hongyun Shi

Role: STUDY_CHAIR

Affiliated Hospital of Hebei University

Weihu Wang

Role: STUDY_CHAIR

Peking University Cancer Hospital & Institute

Jidong Zhang

Role: STUDY_CHAIR

Shanxi Province Cancer Hospital

Central Contacts

Junjie Wang

Role: CONTACT

junjiewang_edu@sina.cn

13701076310

Ping Jiang

Role: CONTACT

drjiangping@qq.com

13439796018

Other Identifiers

BPL-Nim-CC-3003

Identifier Type: -

Identifier Source: org_study_id