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

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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Uterine Cervical Neoplasms
• Intervention / Treatment: Drug: Adjuvant chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 340
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Clinical stage IB3-IIB cervical cancer (FIGO, 2018 standard) with the tumor diameter > 4cm before treatment.
2. Pathologically confirmed cervical cancer, including cervical squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma.
3. Age：18-70 years old.
4. ECOG status score ≤1;
5. 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.
6. Well-compliance and willing to keep in touch.
7. Able to sign informed consent, including complying with the requirements and restrictions listed in the Informed Consent (ICF) and this protocol.

Exclusion Criteria:

1. 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.
2. Neoadjuvant chemotherapy regimens are different from postoperative adjuvant therapy regimens.
3. Postoperative high risk factors: ① lymph node metastasis, ② parauterine infiltration, ③ positive surgical margin.
4. Postoperative risk factors meet the Sedlis standard of the NCCN guideline.
5. Participate in other clinical trials.
6. Severe diseases of other important systems and organs.
7. Persons without disposing capacity.
8. Drug and/or alcohol abuse.
9. Unable or unwilling to sign informed consents.
10. Not eligible for the study judged by researchers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant chemotherapy group; 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; 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.
No Intervention: Control group; The participants receive no intervention.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Collaborators: Qilu Hospital of Shandong University; Hunan Cancer Hospital; The Third Xiangya Hospital of Central South University; Women's Hospital School Of Medicine Zhejiang University; Obstetrics & Gynecology Hospital of Fudan University; First Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): February 1, 2028
• Study Completion (Anticipated): February 1, 2028

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: January 30, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 30, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Cervical Cancer; Locally Advanced Cervical Cancer; Adjuvant Chemotherapy; NACT
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: 2020-S111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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