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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
460
Nimotuzumab 400mg
Cisplatin 40mg/m\^2
External Beam Radiotherapy (EBRT)
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
Time frame: Up to approximately 5 years
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by by the Investigator
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
Time frame: Up to approximately 5 years
3-,5-Year Overall Survival (OS)
OS is the time from randomization to death due to any cause.
Time frame: Up to approximately 3 and 5 years
3-,5-Year Disease Free Survival(DFS)
DFS is defined as the time from randomization to disease recurrence or death due to any cause.
Time frame: Up to approximately 3 and 5 years
3-,5-Year Locoregional Recurrence-Free Survival(LRRFS)
Locoregional recurrence-free survival (LRRFS) was defined as the absence of either consistent or relapsed disease at the primary tumor site or the regional lymph nodes
Time frame: Up to approximately 3 and 5 years
3-,5-Year Distant Metastasis-free Survival (DMFS)
Distant metastasis-free survival (DMFS) was calculated from the date of patient recruitment to the date of distant metastasis.
Time frame: Up to approximately 3 and 5 years
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Brachytherapy
placebo for Nimotuzumab 400mg
Tumor Regression Rate(TRR)
The maximum diameter represents the size of the tumor by MRI. Tumor size for each patient were obtained: pre-RT tumor size (V1), pre- brachytherapy tumor size (V2). TRR=(V1-V2)/V1 × 100%.
Time frame: From date of randomization until the date of brachytherapy,assessed up to 5 weeks
Complete Response Rate
The proportion of subjects with the best complete response in this group assessed by MRI.
Time frame: From date of randomization until the date of brachytherapy,assessed up to 5 weeks
Complete Response Rate
The proportion of subjects with the best complete response in this group assessed by MRI.
Time frame: 3 months later after treatment
Objective Response Rate
The proportion of subjects with the best complete response or partial response in this group assessed by MRI.
Time frame: 3 months later after treatment
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
The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The change from baseline in EORTC QLQ-C30 score will be presented.
Time frame: 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
The EORTC QLQ-CX24 is a questionnaire that rates the symptoms common to women with cervical cancer and evaluates the impact of disease and/or treatments. The 24 items use a 4-point scale (1=not at all to 4=very much) and are classified into 3 multi-item scales, 11 items with symptom experience, 3 items with body image, and 4 items with sexual/ vaginal functioning. The other items of the questionnaire are lymphedema, peripheral neuropathy, menopausal symptom, sexual worry, sexual activity, and sexual enjoyment. The change from baseline in EORTC QLQ-CX24 score will be presented.
Time frame: Baseline and up to approximately 5 years
Incidence of Treatment-Emergent Adverse Events
Safety was assessed as adverse events during treatment, the incidence of various adverse events such as adverse events related to the study drug during treatment, laboratory tests, etc
Time frame: Within 30 days from the start of treatment to the end of the last treatment