Clinical trial NCT06333821: A Study of Nimotuzumab Plus Concurrent Chemoradiotherapy Sequential Maintenance Treatment for Cervical Carcinoma
Official title: A Multicentre, Prospective, Randomized, Double-blind, Placebo-controlled Study of Nimotuzumab Plus Concurrent Chemoradiotherapy Sequential Maintenance Treatment for Locally Advanced Cervical Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Cervical Cancer
Lead sponsor: Biotech Pharmaceutical Co., Ltd.
Sponsor class: OTHER
First posted: 2024-03-27
Enrollment: 460
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter prospective, randomized, double-blind, placebo-controlled phase III trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by by the Investigator
timeFrame: Up to approximately 5 years
measure: 3-,5-Year Overall Survival (OS)
timeFrame: Up to approximately 3 and 5 years
measure: 3-,5-Year Disease Free Survival(DFS)
timeFrame: Up to approximately 3 and 5 years
measure: 3-,5-Year Locoregional Recurrence-Free Survival(LRRFS)
timeFrame: Up to approximately 3 and 5 years
measure: 3-,5-Year Distant Metastasis-free Survival (DMFS)
timeFrame: Up to approximately 3 and 5 years
measure: Tumor Regression Rate(TRR)
timeFrame: From date of randomization until the date of brachytherapy,assessed up to 5 weeks
measure: Complete Response Rate
timeFrame: From date of randomization until the date of brachytherapy,assessed up to 5 weeks
measure: Complete Response Rate
timeFrame: 3 months later after treatment
measure: Objective Response Rate
timeFrame: 3 months later after treatment
measure: 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
timeFrame: Baseline and up to approximately 5 years
measure: 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
timeFrame: Baseline and up to approximately 5 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Within 30 days from the start of treatment to the end of the last treatment
Other outcomes:
Locations:
Study officials:
affiliation: Peking University Third Hospital
name: Junjie Wang
role: STUDY_CHAIR
affiliation: TThe First Affiliated Hospital，the Air Force Medical University
name: Lichun Wei
role: STUDY_CHAIR
affiliation: The Second Affiliated Hospital of Dalian Medical University
name: Lijuan Zou
role: STUDY_CHAIR
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Zi Liu
role: STUDY_CHAIR
affiliation: Ruijin Hospital
name: Jiayi Chen
role: STUDY_CHAIR
affiliation: Henan Cancer Hospital
name: Huijun Cheng
role: STUDY_CHAIR
affiliation: West China Second University Hospital
name: Rutie Yin
role: STUDY_CHAIR
affiliation: Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine.HeBei
name: Xiangkun Yuan
role: STUDY_CHAIR
affiliation: Zhongnan Hospital
name: Hui Qiu
role: STUDY_CHAIR
affiliation: Xiangya Hospital of Central South University
name: Hong Zhu
role: STUDY_CHAIR
affiliation: The Second Norman Bethune Hospital of Jilin University
name: Tiejun Wang
role: STUDY_CHAIR
affiliation: The Fourth Hospital of Hebei Medical University Hebei Tumor Hospital
name: Xiaomei Fan
role: STUDY_CHAIR
affiliation: Hunan Cancer Hospital
name: Keqiang Zhang
role: STUDY_CHAIR
affiliation: Hunan Cancer Hospital
name: Dihong Tang
role: STUDY_CHAIR
affiliation: Second Affiliated Hospital of Nanchang University
name: Qiongyu Lan
role: STUDY_CHAIR
affiliation: The Second Hospital of Hebei Medical University
name: Xiaoying Xue
role: STUDY_CHAIR
affiliation: Shengjing Hospital
name: Song Gao
role: STUDY_CHAIR
affiliation: First Hospital of China Medical University
name: Guang Li
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of Nanchang University
name: Qiuhong Tian
role: STUDY_CHAIR
affiliation: Shanxi Provincial Cancer Hospital
name: Guoqing Wang
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
name: Dong Qian
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of University of South China
name: Manbo Cai
role: STUDY_CHAIR
affiliation: Liaoning Cancer Hospital & Institute
name: Yuhua Gao
role: STUDY_CHAIR
affiliation: Nanfang Hospital, Southern Medical University
name: Dehua Wu
role: STUDY_CHAIR
affiliation: The Affiliated Hospital of Inner Mongolia Medical University
name: Xiaoge Sun
role: STUDY_CHAIR
affiliation: Cancer Hospital Affiliated to Harbin Medical University
name: Yunyan Zhang
role: STUDY_CHAIR
affiliation: Guangxi Medical University Cancer Center
name: Kun Gao
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of Xiamen University
name: Qin Lin
role: STUDY_CHAIR
affiliation: Fujian Cancer Hospital
name: Qin Xu
role: STUDY_CHAIR
affiliation: Peking University Cancer Hospital Inner Mongolia Hospital
name: Hao Yang
role: STUDY_CHAIR
affiliation: First People's Hospital of Foshan
name: Rong Huang
role: STUDY_CHAIR
affiliation: Shenzhen People's Hospital
name: Xianming Li
role: STUDY_CHAIR
affiliation: LanZhou University
name: Juntao Ran
role: STUDY_CHAIR
affiliation: Afﬁliated Hospital of North Sichuan Medical College
name: Xiaojie Ma
role: STUDY_CHAIR
affiliation: Yunnan Cancer Hospital
name: Xingrao Wu
role: STUDY_CHAIR
affiliation: Yantai Yuhuangding Hospital
name: Yipeng Song
role: STUDY_CHAIR
affiliation: Tianjin Cancer Hospital Airport Hospital
name: Jun Wang
role: STUDY_CHAIR
affiliation: Shandong Cancer Hospital ＆ Institute
name: Dapeng Li
role: STUDY_CHAIR
affiliation: Jiangxi Maternal and Child Health Hospital
name: Siyuan Zeng
role: STUDY_CHAIR
affiliation: Affiliated Hospital of Hebei University
name: Hongyun Shi
role: STUDY_CHAIR
affiliation: Peking University Cancer Hospital & Institute
name: Weihu Wang
role: STUDY_CHAIR
affiliation: Shanxi Province Cancer Hospital
name: Jidong Zhang
role: STUDY_CHAIR
References: