Nimotuzumab in Combined With Chemotherapy for Treatment of IVB Stage,Rrecurrent or Persistent Cervical Carcinoma

An Multicenter, Randomized，Double-blind, Controlled Clinical Study of Nimotuzumab in Combined With First-line Chemotherapy for Treatment of IVB Stage,Rrecurrent or Persistent Cervical Squamous Cell Carcinoma

This is an multicenter, randomized，double-blind, controlled clinical study. The purpose of the study is to evaluate the clinical efficacy and safety of Nimotuzumab combined with TP regimen (Paclitaxel + Cisplatin) for treatment of IVB stage, recurrent or persistent cervical squamous cell carcinoma .

Study Overview

• Status: Completed
• Conditions: Cervical Squamous Cell Carcinoma; Persistent
• Intervention / Treatment: Drug: Nimotuzumab; Drug: Paclitaxel; Drug: Cisplatin; Drug: Placebo

Detailed Description

This clinical study is designed as an multicenter, randomized，double-blind, controlled clinical study to evaluate the clinical efficacy and safety of Nimotuzumab combined with TP regimen (Paclitaxel + Cisplatin) for treatment of IVB stage, recurrent or persistent cervical squamous cell carcinoma . The main endpoint is overall survival time, The secondary endpoint is no disease progression time,objective response rate and the quality of life.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Cancer Institute and Hospital , Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary and sign a consent form;
2. Age 18-75 years old ;
3. Histological diagnosis as cervical squamous cell carcinoma ;
4. Histologically and/or cytologically confirmed stage IVB or first recurrent or persistent cervical cancer (Mainly refers to the primary radiotherapy or concurrent chemoradiotherapy at least 3 months after the tumor remains or progress) and patients cannot receive surgery or radiation ;
5. Received taxoplatin + platinum combined chemotherapy stopped taking the drug for at least half a year, or received radiotherapy or concurrent chemoradiotherapy (cisplatin or cisplatin combined with 5-FU) for at least 3 months ;
6. According to the RECIST 1.1 criteria,there is at least one measurable lesion . The maximum diameter must meet the requirements : CT scan ≥10mm (CT scan thickness is less than 5mm); Clinical routine examination instrument 10mm (tumor lesions that cannot be accurately measured by diameter instruments should be recorded as unmeasurable), chest X-ray ≥20mm; Malignant lymph nodes: pathologically enlarged and measurable, single lymph node CT scan diameter ≥15mm (CT scan Layer thickness not more than 5mm) ;
7. Patients need to recover from toxic side effects (except decreased hemoglobin) of previous treatments (surgery, chemoradiotherapy, radiation therapy) to grade 1 or below （CTCAE 4.03）;
8. ECOG performance status 0-1 ;
9. Life expectancy of more than 3 months ;
10. Haemoglobin≥90g/L,white blood cell(WBC)≥4×109/L,Absolute neutrophil count≥1.5×109/L,platelet count≥100×109/L ;
11. TBIL≤1.5 ULN; ALK,AST and ALT≤2.5 ULN or ≤5 ULN(Liver metastasis) ; serum creatinine ≤ 1.5 ULN -

Exclusion Criteria:

1. Simple mediastinal or/and supraclavicular lymph node metastases ;
2. Bone metastases alone or multiple metastases with bone metastases requiring radiotherapy for pain relief ;
3. Patients with recurrence and metastasis after the end of the last administration of neoadjuvant chemotherapy or postoperative adjuvant chemotherapy < 6 months ;
4. Received anti-EGFR monoclonal antibody or small molecule TKI within 6 months prior to enrollment ;
5. Major surgery within 4 weeks or planned surgery or radiation therap ;
6. Participants in other interventional clinical trials within 1 month prior to informed consent ;
7. Neurological or psychiatric abnormalities that affect cognitive ability, including brain metastases ;
8. With clear peripheral neuropathy and related symptoms in the past;
9. Active clinical infection (>grade 2 NCI-CTCAE 4.03), active tuberculosis, and known or self-reported HIV infection or active hepatitis B or C ;
10. Severe respiratory system, blood system disease, intractable dysentery or intestinal cramps, intestinal obstruction, or poorly controlled diabetes ;
11. Uncontrolled hypertension (SBP>160mmHg or DBP>100mmHg), congestive heart failure above NYHA Ⅲ, unstable angina or poorly controlled arrhythmia , circulatory diseases such as myocardial infarction before enrollment within 6 months ;
12. Have allergic reactions to study drugs and similar drugs ;
13. Pregnant or breast-feeding or refused to take contraceptive method;
14. Other malignant tumor;
15. Any other serious complications or dysfunction of the organ system, as judged by the investigator, will affect the safety of the patient or interfere with the evaluation of the test drug ; -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimotuzumab+TP(paclitaxel+cisplatin); experimental group	Drug: Nimotuzumab; Nimotuzumab in combined with chemotherapy period, 400mg, day1, administered intravenously before chemotherapy ,weekly, for 18 weeks; Maintenance period, 400mg, every two weeks until disease progression or intolerable toxicity , maximum duration is 60 weeks .; Other Names: h-R3; Drug: Paclitaxel; 175mg/m^2,for 3 hour,day1,21 days for a cycle ,until disease progression or toxicity，maximum duration is 6 cycles.; Other Names: Paclitaxel Injection; Drug: Cisplatin; 50mg/m^2,day1orday2，21 days for a cycle ,until disease progression or toxicity,maximum duration is 6 cycles.; Other Names: Cisplatin for Injection
Placebo Comparator: Placebo + TP(paclitaxel+cisplatin); control group	Drug: Paclitaxel; 175mg/m^2,for 3 hour,day1,21 days for a cycle ,until disease progression or toxicity，maximum duration is 6 cycles.; Other Names: Paclitaxel Injection; Drug: Cisplatin; 50mg/m^2,day1orday2，21 days for a cycle ,until disease progression or toxicity,maximum duration is 6 cycles.; Other Names: Cisplatin for Injection; Drug: Placebo; Placebo in combined with chemotherapy period, 400mg, day1, administered intravenously before chemotherapy ,weekly, for 18 weeks; Maintenance period, 400mg, every two weeks until disease progression or intolerable toxicity , maximum duration is 60 weeks .; Other Names: Nimotuzumab Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 46 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD.	Up to approximately 46 months
Objective Response Rate	This wil be evaluated by RECISIT 1.1 criteria.It is dependent on imaging evaluation which will be done every 6 weeks. ORR is the percent of the patient who is evaluated as complete response(CR) or partial response (PR),that is (CR+PR)%.	Up to approximately 46 months
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.	Baseline and up to approximately 46months
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.	Baseline and up to approximately 46months

Collaborators and Investigators

• Sponsor: Biotech Pharmaceutical Co., Ltd.
• Investigators: Study Chair: lingying wu, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): November 25, 2024
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: cisplatin; paclitaxel; Nimotuzumab
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Paclitaxel; Cisplatin; Nimotuzumab
• Other Study ID Numbers: BPL-Nim-CC-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No