Neoadjuvant Chemotherapy Plus Camrelizumab for FIGO Stage IB1 Cervical Cancer

Phase 2

Recruiting

• Conditions: Cervical Cancer; Neoadjuvant Chemoimmunotherapy; Fertility Preservation
• Interventions: Drug: Camrelizumab; Drug: Cisplatin; Drug: Nab paclitaxel; Procedure: biopsy

• Registration Number: NCT06289062
• Lead Sponsor: Tongji Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-02-19
• Study First Submitted QC: 2024-02-24
• Study First Posted: 2024-03-01
• Study Start: 2024-05-08
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-12-01
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NACI in FIGO ⅠB1 Cervical Cancer	Camrelizumab	Neoadjuvant chemotherapy plus camrelizumab for ⅠB1 Cervical Cancer. Patients first received one cycle of platinum-based doublet priming chemotherapy. After 3 weeks, participants subsequently received two cycles of the PD-1 inhibitor camrelizumab combined with chemotherapy every 3 weeks. The study will be conducted in two stages: (1) Patients enrolled in the first stage with tumors ≤2 cm and no new lesions after completion of treatment will undergo cone biopsy + pelvic lymphadenectomy or SLN mapping. Those who meet ConCerv criteria will undergo a second TCT, human papillomavirus (HPV) and colposcope 3 months later, and those who do not meet ConCerV criteria will undergo radical cervical surgery. (2) Patients enrolled in the second stage with tumors ≤2 cm and no new lesions underwent cervical biopsy + pelvic lymphadenectomy or SLN mapping; patients with LSIL on biopsy underwent TCT, HPV, and colposcope 3 months later; if biopsy suggests HSIL and above, perform cone biopsy.
NACI in FIGO ⅠB1 Cervical Cancer	Cisplatin	Neoadjuvant chemotherapy plus camrelizumab for ⅠB1 Cervical Cancer. Patients first received one cycle of platinum-based doublet priming chemotherapy. After 3 weeks, participants subsequently received two cycles of the PD-1 inhibitor camrelizumab combined with chemotherapy every 3 weeks. The study will be conducted in two stages: (1) Patients enrolled in the first stage with tumors ≤2 cm and no new lesions after completion of treatment will undergo cone biopsy + pelvic lymphadenectomy or SLN mapping. Those who meet ConCerv criteria will undergo a second TCT, human papillomavirus (HPV) and colposcope 3 months later, and those who do not meet ConCerV criteria will undergo radical cervical surgery. (2) Patients enrolled in the second stage with tumors ≤2 cm and no new lesions underwent cervical biopsy + pelvic lymphadenectomy or SLN mapping; patients with LSIL on biopsy underwent TCT, HPV, and colposcope 3 months later; if biopsy suggests HSIL and above, perform cone biopsy.
NACI in FIGO ⅠB1 Cervical Cancer	Nab paclitaxel	Neoadjuvant chemotherapy plus camrelizumab for ⅠB1 Cervical Cancer. Patients first received one cycle of platinum-based doublet priming chemotherapy. After 3 weeks, participants subsequently received two cycles of the PD-1 inhibitor camrelizumab combined with chemotherapy every 3 weeks. The study will be conducted in two stages: (1) Patients enrolled in the first stage with tumors ≤2 cm and no new lesions after completion of treatment will undergo cone biopsy + pelvic lymphadenectomy or SLN mapping. Those who meet ConCerv criteria will undergo a second TCT, human papillomavirus (HPV) and colposcope 3 months later, and those who do not meet ConCerV criteria will undergo radical cervical surgery. (2) Patients enrolled in the second stage with tumors ≤2 cm and no new lesions underwent cervical biopsy + pelvic lymphadenectomy or SLN mapping; patients with LSIL on biopsy underwent TCT, HPV, and colposcope 3 months later; if biopsy suggests HSIL and above, perform cone biopsy.
NACI in FIGO ⅠB1 Cervical Cancer	biopsy	Neoadjuvant chemotherapy plus camrelizumab for ⅠB1 Cervical Cancer. Patients first received one cycle of platinum-based doublet priming chemotherapy. After 3 weeks, participants subsequently received two cycles of the PD-1 inhibitor camrelizumab combined with chemotherapy every 3 weeks. The study will be conducted in two stages: (1) Patients enrolled in the first stage with tumors ≤2 cm and no new lesions after completion of treatment will undergo cone biopsy + pelvic lymphadenectomy or SLN mapping. Those who meet ConCerv criteria will undergo a second TCT, human papillomavirus (HPV) and colposcope 3 months later, and those who do not meet ConCerV criteria will undergo radical cervical surgery. (2) Patients enrolled in the second stage with tumors ≤2 cm and no new lesions underwent cervical biopsy + pelvic lymphadenectomy or SLN mapping; patients with LSIL on biopsy underwent TCT, HPV, and colposcope 3 months later; if biopsy suggests HSIL and above, perform cone biopsy.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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.
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
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
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
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.
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
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

Trial Locations

Locations (2)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China