Trial Title:
Neoadjuvant Chemoimmunotherapy Versus Concurrent Chemoradiotherapy for LACC
NCT ID:
NCT06288373
Condition:
Cervical Cancer
Locally Advanced Cervical Cancer
Concurrent Chemoradiotherapy
Neoadjuvant Chemoimmunotherapy
Conditions: Official terms:
Uterine Cervical Neoplasms
Paclitaxel
Cisplatin
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Camrelizumab
Description:
Camrelizumab is administered at 200mg, q3w (second and third cycles) before radical
surgery
Arm group label:
Camrelizumab combined neoadjuvant chemotherapy plus radical surgery
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin:75-80mg/m2, D1-D2,q3w (3 cycles),intravenous infusion, administered at a rate
of 1mg/min.
Arm group label:
Camrelizumab combined neoadjuvant chemotherapy plus radical surgery
Intervention type:
Drug
Intervention name:
Nab paclitaxel
Description:
Nab paclitaxel: 260 mg/m2,D1,q3w (3 cycles),intravenous infusion, administered over
30min.
Arm group label:
Camrelizumab combined neoadjuvant chemotherapy plus radical surgery
Intervention type:
Procedure
Intervention name:
Radical surgery
Description:
Radical surgery
Arm group label:
Camrelizumab combined neoadjuvant chemotherapy plus radical surgery
Intervention type:
Radiation
Intervention name:
external beam radiation therapy (EBRT) + brachytherapy
Description:
Radiation therapy per standard of care
Arm group label:
Concurrent Chemoradiotherapy (CCRT)
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Chemotherapy administered concurrent with radiation therapy,cisplatin 40 mg/m2 IV once
per week (QW) for 5 weeks
Arm group label:
Concurrent Chemoradiotherapy (CCRT)
Summary:
It is a prospective, open-label, randomized, controlled phase II/III clinical trial in
which patients with PD-L1-positive FIGO stage IB3, IIA2 and IIB(tumors >4 cm in
diameter)will be enrolled and randomly divided into the neoadjuvant chemoimmunotherapy
plus surgery group and the CCRT group.
Detailed description:
Cervical cancer is the most common gynecological malignancy in China, with locally
advanced cervical cancer (LACC) accounting for approximately 37% of cases. Currently, the
recommended standard of care for LACC according to international guidelines is concurrent
chemoradiotherapy (CCRT). However, the impacts of radiation therapy on patients' quality
of life are increasingly being recognized. Additionally, 23.3% to 34.4% of patients still
face recurrence or metastasis after treatment, and the 5-year overall survival rate
remains around 75%.
Neoadjuvant chemotherapy (NACT) is a chemotherapy regimen used prior to surgery for LACC.
NACT followed by radical surgery has a similar overall survival compared to CCRT, but the
disease-free survival is relatively lower with NACT. Moreover, 9.8% to 30.6% of patients
show poor response to NACT, and over 30% of patients require postoperative adjuvant
therapy. These issues significantly limit the application of NACT in LACC.
In recent years, immunotherapy has made significant progress in advanced or recurrent
cervical cancer. A phase II clinical trial of combination of PD-1 inhibitors and
neoadjuvant chemotherapy showed significant anti-tumor activity and safety. Therefore,
based on the preliminary results, this project aims to conduct a multicenter,
prospective, randomized controlled clinical trial to further confirm the value of
neoadjuvant immunotherapy combined with surgery in LACC. It will be compared with the
standard CCRT regimen to explore the differences in clinical efficacy and adverse events
between the two groups, providing high-level evidence for the application of neoadjuvant
immunotherapy in cervical cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Locally advanced (2018 FIGO staged IB3, IIA2 and IIB(tumor size> 4cm) ) cervical
cancer,staging determined by two physicians of associate seniority or higher after
gynecologic examination and imaging evaluation);
2. At least one measurable lesion at baseline according to RECIST 1.1 criteria, with
lesion size based primarily on magnetic resonance imaging;
3. Pathologically confirmed diagnosis of cervical cancer, including cervical squamous
cell carcinoma, adenocarcinoma (common type), and adenosquamous carcinoma;
4. Positive PD-L1 expression, Combined Positive Score (CPS) ≥1;
5. Patient age ≥18 years and ≤70 years;
6. ECOG score ≤1;
7. Laboratory tests: WBC (white blood cell count) ≥ 3.5×109/L, NEU (neutrophil count) ≥
1.5×109/L, PLT (platelet count) ≥ 100×109/L, total bilirubin ≤ 1.5 times the upper
limit of normal, ALT (alanine aminotransferase) and AST (aspartate aminotransferase)
≤ 1.5 times the upper limit of normal, serum creatinine (BUN) ≤ 1.5 times the upper
limit of normal or creatinine clearance ≥ 50 mL/min (calculated using the
Cockcroft-Gault formula, the Chronic Kidney Disease Epidemiology Collaboration
equation, or the Modification of Diet in Renal Disease equation);
8. Be willing to follow up and good compliance;
9. Be willing to sign the informed consent, including compliance with the requirements
and restrictions listed in the informed consent and program;
10. Agree to use effective contraception measures during the trial period and for 5
months after the last dose of pembrolizumab or 6 months after chemotherapy
(whichever is longer).
Exclusion Criteria:
1. Any active autoimmune disease or history of autoimmune disease requiring systemic
treatment, including but not limited to autoimmune hepatitis, interstitial
pneumonitis, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis,
nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring bronchodilator
intervention;
2. Prior treatment with immune checkpoint inhibitors, including but not limited to
other anti-PD-1 and anti-PD-L1 antibodies; known hypersensitivity to any component
of the study medication or other monoclonal antibodies;
3. Has a history of human immunodeficiency virus (HIV) infection, active hepatitis B
(HBV-DNA ≥ 2000 IU/mL or 104 copies/mL), and hepatitis C (HCV antibody positive, and
HCV-RNA above the lower limit of detection of the assay);
4. Receipt of immunosuppressive medications or systemic corticosteroid therapy for
immunosuppression (>10 mg/day prednisone or equivalent) within 2 weeks prior to
study dosing;
5. Diagnosed with another primary malignancy within 5 years prior to the first use of
the investigational drug;
6. Received other investigational drugs/treatments or participated in another clinical
trial within 4 weeks prior to randomization. Participation in observational and
non-interventional clinical trials is allowed;
7. Pregnant or breastfeeding female patients;
8. Uncontrolled co-morbidities, including but not limited to New York Heart Association
(NYHA) class 2 or higher, severe/unstable angina pectoris, myocardial infarction
within ≤ 6 months prior to study drug administration, severe arrhythmias requiring
medication or intervention; difficult-to-control hypertension; cerebral vascular
accidents or brain disorders within ≤ 6 months prior to study drug administration,
or individuals with adjudicated abnormal behavioral skills; hematologic disorders:
coagulation abnormalities (INR >2. 0, PT>16s), bleeding tendency, or undergoing
thrombolytic or anticoagulant therapy; abnormalities in hepatic or renal development
or a history of surgery; and development of an active infection requiring systemic
anti-infective therapy within 14 days prior to the first dose of study drug;
9. Treatment with a live or attenuated vaccine administered within 4 weeks prior to the
first dose of study drug; inactivated seasonal influenza virus vaccine is permitted;
10. Patients with a prior allogeneic bone marrow or solid organ transplant;
11. Drug and/or alcohol abuse;
12. Patients who, in the opinion of the investigator, are unlikely to comply with the
procedures, restrictions, and requirements of the study may not be enrolled in the
study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Anhui Provincial Cancer Hospital
Address:
City:
Hefei
Zip:
230000
Country:
China
Status:
Recruiting
Contact:
Last name:
Bairong Xia, PhD
Email:
xiabairong@ustc.edu.cn
Investigator:
Last name:
Bairong Bairong, PhD
Email:
Principal Investigator
Facility:
Name:
Beiing Friendship Hospital, Capital Medical University
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhiqi Wang, PhD
Email:
wangzqnet@sina.com
Investigator:
Last name:
Zhiqi Zhiqi, PhD
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital (Southwest Hospital), Army Medical University (Third Military Medical University)
Address:
City:
Chongqing
Zip:
400038
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanzhou Wang, PhD
Email:
w.y.z@foxmail.com
Investigator:
Last name:
Yanzhou Yanzhou, PhD
Email:
Principal Investigator
Facility:
Name:
Gansu Provincial Maternity and Child-care Hospital
Address:
City:
Lanzhou
Zip:
730050
Country:
China
Status:
Recruiting
Contact:
Last name:
Yun Dang, PhD
Investigator:
Last name:
Yun Dang, PhD
Email:
Principal Investigator
Facility:
Name:
The Affiliated Tumor Hospital of Guangxi Medical University
Address:
City:
Nanning
Zip:
530021
Country:
China
Status:
Recruiting
Contact:
Last name:
Ying Long, PhD
Investigator:
Last name:
Ying Long, PhD
Email:
Principal Investigator
Facility:
Name:
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Recruiting
Contact:
Last name:
Kezhen Li
Phone:
086-027-8362
Email:
tjkeke@126.com
Contact backup:
Last name:
Jing Chen
Phone:
086-027-8362
Email:
chenjing3223@126.com
Investigator:
Last name:
Kezhen Li
Email:
Principal Investigator
Investigator:
Last name:
Gang Chen
Email:
Principal Investigator
Facility:
Name:
Xiangya Hospital, Central South University
Address:
City:
Changsha
Zip:
410008
Country:
China
Status:
Recruiting
Contact:
Last name:
Yu Zhang, PhD
Email:
xyzhangyu@csu.edu.cn
Investigator:
Last name:
Yu Zhang, PhD
Email:
Principal Investigator
Facility:
Name:
Shengjing Hospital of China Medical University
Address:
City:
Shenyang
Country:
China
Status:
Recruiting
Contact:
Last name:
Tingting Gong, PhD
Email:
gongtt@sj-hospital.org
Investigator:
Last name:
Tingting Gong, PhD
Email:
Principal Investigator
Facility:
Name:
Second People's Hospital of Sichuan (Sichuan Cancer Hospital)
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Dengfeng Wang, PhD
Investigator:
Last name:
Dengfeng Wang, PhD
Email:
Principal Investigator
Facility:
Name:
Tianjin Medical University General Hospital
Address:
City:
Tianjin
Country:
China
Status:
Recruiting
Contact:
Last name:
Yingmei Wang, PhD
Email:
wangyingmei@tmu.edu.cn
Investigator:
Last name:
Yingmei Yingmei, PhD
Email:
Principal Investigator
Facility:
Name:
Women's Hospital, Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Yuanming Shen, PhD
Email:
5312010@zju.edu.cn
Investigator:
Last name:
Yuanming Shen, PhD
Email:
Principal Investigator
Facility:
Name:
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Yingli Zhang, PhD
Email:
zhangyl@zjcc.org.cn
Investigator:
Last name:
Yingli Zhang, PhD
Email:
Principal Investigator
Start date:
April 22, 2024
Completion date:
March 1, 2031
Lead sponsor:
Agency:
Tongji Hospital
Agency class:
Other
Collaborator:
Agency:
Southwest Hospital, China
Agency class:
Other
Collaborator:
Agency:
Women Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Collaborator:
Agency:
Anhui Provincial Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Sichuan Cancer Hospital and Research Institute
Agency class:
Other
Collaborator:
Agency:
Qilu Hospital of Shandong University
Agency class:
Other
Collaborator:
Agency:
Beijing Friendship Hospital
Agency class:
Other
Collaborator:
Agency:
Tianjin Medical University General Hospital
Agency class:
Other
Collaborator:
Agency:
West China Second University Hospital
Agency class:
Other
Collaborator:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Xiangya Hospital of Central South University
Agency class:
Other
Collaborator:
Agency:
Gansu Provincial Maternal and Child Health Care Hospital
Agency class:
Other
Collaborator:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Shengjing Hospital
Agency class:
Other
Collaborator:
Agency:
Cancer Hospital of Guangxi Medical University
Agency class:
Other
Source:
Tongji Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06288373