Clinical Efficacy of Adjuvant Chemotherapy in Patients With Locally Advanced Cervical Cancer Who Did Not Meet the NCCN Guidelines for Adjuvant Treatment After NACT Combined With Surgery

Study Overview
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Brief Summary
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This is a prospective, phase 3 randomized controlled clinical trial. Cervical cancer patients with FIGO stage IB3, Ⅱ A2 or IIB with tumor size> 4 cm will be enrolled. Patients will undergo 2-3 cycles of neoadjuvant chemotherapyradical (NACT) followed by laparotomic or laparoscopic hysterectomy + pelvic lymphadenectomy with cervical cancer foci sealed before dissection of the vagina and without uterine manipulator. Patients meet criteria of adjuvant therapy according to NCCN guideline after surgery will be weeded out, and who do not meet criteria of adjuvant therapy will be randomly selected to undergo adjuvant chemotherapy or just follow-up visit. The primary endpoint was disease-free survival (DFS) rate at 5 year. The secondary endpoints were 5-year overall survival (OS), safety and quality of life.

Official Title
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Clinical Efficacy of Adjuvant Chemotherapy in Patients With Locally Advanced Cervical Cancer Who Did Not Meet the NCCN Guidelines for Adjuvant Treatment After NACT Combined With Surgery

Conditions
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Uterine Cervical Neoplasms, Cervical Cancer

Intervention / Treatment
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* Drug: Adjuvant chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical stage IB3-IIB cervical cancer (FIGO, 2018 standard) with the tumor diameter > 4cm before treatment. Pathologically confirmed cervical cancer, including cervical squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. Age：18-70 years old. ECOG status score ≤1; WBC≥3.5*10^9/L, NEU≥1.5*10^9/L, Platelet≥80×10^9 /L; AST and ALT ≤1.5 times normal upper limit; Total bilirubin ≤1.5 times the upper limit of normal value; serum creatinine and blood urea nitrogen ≤the upper limit of normal value. Well-compliance and willing to keep in touch. Able to sign informed consent, including complying with the requirements and restrictions listed in the Informed Consent (ICF) and this protocol. Exclusion Criteria: After 2-3 cycles of neoadjuvant chemotherapy, patients do not undergo laparotomic or laparoscopic extensive hysterectomy + pelvic lymph node dissection with cervical cancer foci sealed before dissection of the vagina and without uterine manipulator. Neoadjuvant chemotherapy regimens are different from postoperative adjuvant therapy regimens. Postoperative high risk factors: ① lymph node metastasis, ② parauterine infiltration, ③ positive surgical margin. Postoperative risk factors meet the Sedlis standard of the NCCN guideline. Participate in other clinical trials. Severe diseases of other important systems and organs. Persons without disposing capacity. Drug and/or alcohol abuse. Unable or unwilling to sign informed consents. Not eligible for the study judged by researchers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant chemotherapy group<br>Participant will receive at least 2 cycles of adjuvant chemotherapy. If having any of the following factors, participant will receive additional 2 cycles of adjuvant chemotherapy per risk factor. All patients received maximum 6 cycles of postoperative chemotherapy. Risk factors: (1) Deep cervical invasion（≥ 2/3）；（2）Differentiation grade 2-3；（3）Lymphatic vascular space infiltration；（4）Adenocarcinoma or adenosquamous carcinoma；（5）Tumor size ≥ 4cm before surgery. | Drug: Adjuvant chemotherapy<br>* Drug: Paclitaxel or docetaxel + Cisplatin or carboplatin Paclitaxel 135-175mg/m2 over 3 hours or docetaxel 70-75 mg/m2， 30min ＋ Cisplatin 75-80mg/m2 or carboplatin AUC = 5, repeat per 21 days.<br>|
| No Intervention: Control group<br>The participants receive no intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) | DFS is defined as the time interval between the date of random assignment and the date of the first documented evidence of relapse at any site or death related to cancer (including toxicity), whichever occurred first. | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival （OS） | OS is defined as the time from the date of randomization until death of any cause. | 5 year | 
| Quality of Life Outcomes | Patients are asked to complete the questionnaire EORTC QLQ-C30 | 5 years | 
| Quality of Life Outcomes of cervical cancer | Patients are asked to complete the questionnaire EORTC QLQ-CX24 | 5 years | 
| Incidence of Toxicity | The toxicity induced by chemotherapy during observation time will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 5.0. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical Cancer, NACT, Adjuvant Chemotherapy, Locally Advanced Cervical Cancer