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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Camrelizumab is administered at 200mg, q3w (second and third cycles) before radical surgery
Cisplatin:75-80mg/m2, D1-D2,q3w (3 cycles),intravenous infusion, administered at a rate of 1mg/min.
Nab paclitaxel: 260 mg/m2,D1,q3w (3 cycles),intravenous infusion, administered over 30min.
Anhui Provincial Cancer Hospital
Hefei, Anhui, China
RECRUITINGBeiing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Progression-free survival, PFS
PFS is defined as the time from randomisation to tumor progression, postoperative relaspse or metastasis, or death, which occur first.
Time frame: 7 years
Objective Response Rate, ORR
The proportion of patients who had either complete response or partial response, assessed by independent central reviewers according to RECIST, version 1.1.
Time frame: 2 years
Overall survival, OS
OS is defined as the time from randomisation to death.
Time frame: 7 years
Proportion of patients undergoing radical surgery
Proportion of patients undergoing radical surgery for neoadjuvant chemoimmunotherapy plus surgery group
Time frame: 2 years
Pathologic Complete Response
Pathologic complete response (pCR) refers to the absence of invasive/in situ cancer in the cervical and/or lymph nodes.
Time frame: 2 years
The surgical complication rate
Intraoperative bleeding, vascular injuries, bladder injuries, rectal injuries, and ureteral injuries were measured by the need for suture repair; occlusive nerve injuries were measured by complete severance, and vascular injuries required documentation of the site of injury. Postoperative complications included: cervical stenosis, cervical insufficiency, ureteral/bladder/rectal/vaginal fistula, internal hemorrhage, pelvic infection, lymphocyst, lymphatic fistula, lower extremity edema, lower extremity venous thrombosis, urinary retention, nerve injury, and bowel obstruction.
Time frame: 2 years
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Enrollment
440
Radical surgery
Radiation therapy per standard of care
Chemotherapy administered concurrent with radiation therapy,cisplatin 40 mg/m2 IV once per week (QW) for 5 weeks
The First Affiliated Hospital (Southwest Hospital), Army Medical University (Third Military Medical University)
Chongqing, Chongqing Municipality, China
RECRUITINGGansu Provincial Maternity and Child-care Hospital
Lanzhou, Gansu, China
RECRUITINGThe Affiliated Tumor Hospital of Guangxi Medical University
Nanning, Guangxi, China
RECRUITINGTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGXiangya Hospital, Central South University
Changsha, Hunan, China
RECRUITINGShengjing Hospital of China Medical University
Shenyang, Liaoning, China
RECRUITINGSecond People's Hospital of Sichuan (Sichuan Cancer Hospital)
Chengdu, Sichuan, China
RECRUITINGTianjin Medical University General Hospital
Tianjin, Tianjin Municipality, China
RECRUITING...and 2 more locations
Safety and toleraty
The incidence of adverse evetns, severe adverse events; surgery related safety.
Time frame: 7 years
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Function Score
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.
Time frame: 7 years
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.
Time frame: 7 years