Cervical Cancer
Conditions
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.
Interventions
BIOLOGICALNimotuzumab
Nimotuzumab 400mg
DRUGCisplatin
Cisplatin 40mg/m\^2
RADIATIONExternal Beam Radiotherapy (EBRT)
External Beam Radiotherapy (EBRT)
RADIATIONBrachytherapy
Brachytherapy
DRUGplacebo for Nimotuzumab
placebo for Nimotuzumab 400mg
Sponsors
Biotech Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
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).
Intervention model description
This is a multicenter prospective, randomized, double-blind, placebo-controlled phase III trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed Blinded Independent Central Review (BICR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-,5-Year Overall Survival (OS) | Up to approximately 3 and 5 years | OS is the time from randomization to death due to any cause. |
| 3-,5-Year Disease Free Survival(DFS) | Up to approximately 3 and 5 years | DFS is defined as the time from randomization to disease recurrence or death due to any cause. |
| 3-,5-Year Locoregional Recurrence-Free Survival(LRRFS) | Up to approximately 3 and 5 years | 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 |
| 3-,5-Year Distant Metastasis-free Survival (DMFS) | Up to approximately 3 and 5 years | Distant metastasis-free survival (DMFS) was calculated from the date of patient recruitment to the date of distant metastasis. |
| Tumor Regression Rate(TRR) | From date of randomization until the date of brachytherapy,assessed up to 5 weeks | 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%. |
| 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 | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. |
| Objective Response Rate | 3 months later after treatment | The proportion of subjects with the best complete response or partial response in this group assessed by MRI. |
| 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 | 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. |
| 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 | 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. |
| Incidence of Treatment-Emergent Adverse Events | Within 30 days from the start of treatment to the end of the last treatment | 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 |
| Complete Response Rate | From date of randomization until the date of brachytherapy,assessed up to 5 weeks | The proportion of subjects with the best complete response in this group assessed by MRI. |
Contacts
Primary ContactJunjie Wang
Backup ContactPing Jiang
Outcome results
None listed