Cervical Cancer, Fertility Preservation, Neoadjuvant Chemoimmunotherapy
Conditions
Brief summary
This multicenter, prospective clinical trial is designed to enroll PD-L1 expression-positive patients with stage IB1 cervical cancer who desire fertility preservation to undergo neoadjuvant chemotherapy in combination with a PD-1 inhibitor to evaluate the rate of complete pathologic remission, treatment-related adverse events, pregnancy rate, miscarriage rate, preterm birth rate, live birth rate, EFS and OS.
Interventions
DRUGCamrelizumab
Camrelizumab is administered at 200mg, q3w (second and third cycles) before radical surgery
DRUGCisplatin
75-80mg/m2, D1-D2，q3w (3 cycles)，intravenous infusion, administered at a rate of 1mg/min.
DRUGNab paclitaxel
260 mg/m2，D1，q3w （3 cycles），intravenous infusion, administered over 30min.
PROCEDUREbiopsy
cone biopsy + pelvic lymphadenectomy or Cervical biopsy + pelvic lymphadenectomy
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Women's Hospital School Of Medicine Zhejiang University
Third Military Medical University
Beijing Friendship Hospital
Sichuan Cancer Hospital and Research Institute
Tianjin Medical University
West China Second University Hospital
Xiangya Hospital of Central South University
Qilu Hospital of Shandong University
Gansu Cancer Hospital
Zhejiang Cancer Hospital
Shengjing Hospital
Anhui Provincial Cancer Hospital
Tongji Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of stage IB1 cervical cancer after gynecologic examination and MRI evaluation by the investigator (FIGO 2018); 2. Pathologically confirmed diagnosis of cervical squamous cell carcinoma; 3. Transformation zone of TZ1 or TZ2 (IFCPC 2011); 4. Positive PD-L1 expression by preoperative pathology, i.e., Combined Positive Score (CPS) ≥1; 5. Patient age ≥18 years and ≤45 years; 6. ECOG score ≤1; 7. Laboratory tests: white blood cell (WBC) ≥3. 5×109/L, Neutrophil (NEU) ≥1. 5×109/L, platelet (PLT) ≥100×109/L, serum bilirubin ≤1.5 times the upper limit of normal, aminotransferase ≤1.5 times the upper limit of normal, and blood urea nitrogen （BUN) and Cr ≤normal; 8. Have a strong desire to give birth; 9. Willing to sign the informed consent form, including compliance with the requirements and restrictions listed in the informed consent form and program.
Exclusion criteria
1. History of infertility, including those with infertility due to tubal or (and) husband; 2. Any active autoimmune disease or history of autoimmune disease requiring systemic treatment, including, but not limited to, autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring bronchodilator intervention; 3. 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; 4. History of human immunodeficiency virus (HIV) infection or known active hepatitis B or C; 5. Use of immunosuppressive drugs or systemic corticosteroid therapy for immunosuppression (\>10 mg/day prednisone or equivalent) within 2 weeks prior to study dosing; 6. History of primary malignancy or receipt of chemotherapy or pelvic radiation; 7. Concurrent participation in other clinical trials; 8. Pregnant or breastfeeding female patients; subjects must agree to use effective contraception during study treatment, within 5 months of last use of immune check inhibitors, within 6 months of last use of chemotherapeutic agents, and if there is no confirmation that the lesion has been removed or that the pathology is in remission; 9. 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; and cerebral vascular accidents or brain disorders within ≤ 6 months prior to study drug administration, or those with adjudicated abnormal behavioral skills; hematologic disorders: coagulation abnormalities (INR \> 2. 0, Prothrombin time (PT) \> 16s), bleeding tendency, or undergoing thrombolytic or anticoagulant therapy; abnormalities in hepatic or renal development or a history of surgery; and any active infection requiring systemic anti-infective therapy within 14 days prior to the first dose of study drug; 10. Treatment with live or attenuated vaccine within 4 weeks prior to the first dose of study drug; inactivated seasonal influenza virus vaccine is permitted; 11. Patients who have received a previous allogeneic bone marrow or solid organ transplant; 12. Drug and/or alcohol abuse; 13. Patients who, in the opinion of the investigator, are unlikely to comply with the study procedures, restrictions, and requirements may not participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response | At the end of the patient's treatment, up to 2 years. | Proportion of patients with no tumor cells on postoperative pathology and negative lymph node metastasis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy rate | Until the end of the 5-year follow-up period, up to 7 years. | the ratio of the number of women with a successful pregnancy to the total number of women who attempted to become pregnant |
| Miscarriage rate | Until the end of the 5-year follow-up period, up to 7 years. | the ratio of miscarriage events that occur during pregnancy in women who are pregnant |
| Live birth rate | Until the end of the 5-year follow-up period, up to 7 years. | The live birth rate is the ratio of the number of babies successfully delivered and surviving to the total number of women who attempted pregnancy |
| Preterm birth rate | Until the end of the 5-year follow-up period, up to 7 years. | The preterm birth rate is the proportion of babies born at less than 37 weeks of gestation |
| Adverse Event | during the treatment, up to 5 years. | Adverse Effects of immunotherapy and chemotherapy |
| The negative conversion of HPV | At the end of treatment, up to 2 years. | Proportion of patients with known HPV infection at screening who are HPV-negative after treatment |
| Patient Reported Outcomes (EORTC QLQ-C30) | From enrollment to the end of the 5-year follow-up period. 5 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 |
| Patient Reported Outcomes (EORTC QLQ-CX24) | From enrollment to the end of the 5-year follow-up period. 5 years. | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (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. |
| Event-free survival (EFS) | Until the end of the 5-year follow-up period, up to 7 years. | the time between the enrollment and any documented tumor progression, recurrence, or death from any cause; the analysis of EFS includes the results of tumor evaluations during the study treatment and follow-up periods. If a patient had several indicators of progressive disease (PD) or recurrence, the EFS analysis was performed using the indicator that appeared first; PD, recurrence, or death were considered to have reached the study endpoint; patients who were treated with other systemic or antitumor therapies directed at the target lesion of observation were also considered to be in PD; for patients who did not have PD, recurrence, or death at the end of the study, the time when the patient's failure to have a recurrence was last obtained was used as the time to censor the data. |
| Overall survival (OS) | Until the end of the 5-year follow-up period, up to 7 years. | the time from the start of enrollment to death from any cause |
| Number of Participants with surgical complications | During and after the surgery, up to 2 years. | intraoperative bleeding, vascular injuries, bladder injuries, rectal injuries, and ureteral injuries, as defined by the need for suture repair; occlusive nerve injuries, as defined by complete severance; and vascular injuries, as defined by the need to document 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. |
Countries
China
Contacts
Primary ContactKezhen Li
Backup ContactJing Chen
Outcome results
None listed