Postoperative Adjuvant Chemotherapy in Early-stage Cervical Cancer That Not Meet Criteria of Adjuvant Therapeutic According to NCCN Guideline

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 who undergo radical surgery but do not meet criteria of adjuvant therapy according to NCCN guideline are enrolled to receive adjuvant chemotherapy. The primary endpoint was disease-free survival (DFS) rate at 3 year. The secondary endpoints were 5-year DFS, overall survival (OS) and safety.

Official Title
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Postoperative Adjuvant Chemotherapy in Early-stage Cervical Cancer That Not Meet Criteria of Adjuvant Therapeutic According to NCCN Guideline：A Prospective Multicenter Randomized Controlled Clinical Trial

Conditions
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Uterine Cervical Neoplasms, Cervical Cancer

Intervention / Treatment
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* Drug: Paclitaxel or docetaxel + Cisplatin or carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with 2018 FIGO staged IB1，IB2, IIA1 cervical cancer. The initial treatment was radical hysterectomy + pelvic lymphadenectomy by laparotomy or laparoscopy with cervical cancer foci sealed before dissection of the vagina and without uterine manipulator. Postoperative pathological diagnosis was cervical squamous cell carcinoma, cervical adenosquamous cell carcinoma or cervical adenocarcinoma. Assessment of risk factors not meeting Sedlis criteria （NCCN guideline），but having one of following factors ：（1）Deep stromal infiltration（≥2/3 layer）；（2）histopathological differentiation grade G2   G3；（3）Lymph-vascular space invasion ；（4）Adenocarcinoma or adenosquamous cell carcinoma；（5）Tumor size ≥2cm. Age：18-70 years old. 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. Eastern Cooperative Oncology Group score 0-1. Well-compliance and willing to keep in touch. Willing to participate in this study, and sign the informed consent. Exclusion Criteria: Postoperative pathology has high-risk factors（lymph node metastasis, parametrial infiltration or positive surgical margin）or meets Sedlis criteria. Participate in other clinical trials at the same time. Comorbidity including but not limited to: heart diseases (grade III-IV cardiac insufficiency (NYHA standard); central nervous system diseases or nonfunctional behavior; hematological system diseases; liver or kidney malformation or history of surgery. 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 3 cycles of adjuvant chemotherapy if having any of the following factors；participant will receive 6 cycles of adjuvant chemotherapy if having ≥2 of the following factors. 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 ≥ 2cm | Drug: Paclitaxel or docetaxel + Cisplatin or carboplatin<br>* 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. | 3 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. | 3 year | 
| 5-year DFS/OS | 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. OS is defined as the time from the date of randomization until death of any cause. | 5 years |