Neoadjuvant Chemotherapy Plus Camrelizumab for FIGO Stage IB1 Cervical Cancer

Cervical Cancer Clinical Trial

Official title:

Neoadjuvant Chemotherapy Plus Camrelizumab (NACI Therapy) for Fertility Preservation in FIGO Stage IB1 Cervical Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06289062
• Other study ID #: NACI-CERV-005
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2024
• Est. completion date: December 1, 2030

Study information

• Verified date: February 2024
• Source: Tongji Hospital
• Contact: Kezhen Li
• Phone: 086-027-8362
• Email: tjkeke[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, PFS and OS.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 1, 2030
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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: WBC =3. 5×109/L, NEU =1. 5×109/L, PLT =100×109/L, serum bilirubin =1.5 times the upper limit of normal, aminotransferase =1.5 times the upper limit of normal, and 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, 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.

Related Conditions & MeSH terms

• Cervical Cancer
• Fertility Preservation
• Uterine Cervical Neoplasms

Intervention

Drug:
• Camrelizumab
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.

Procedure:
• biopsy
cone biopsy + pelvic lymphadenectomy or Cervical biopsy + pelvic lymphadenectomy

Locations

Country	Name	City	State
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (14)

Lead Sponsor

Collaborator

Tongji Hospital

Anhui Provincial Cancer Hospital, Beijing Friendship Hospital, Gansu Cancer Hospital, Qilu Hospital of Shandong University, Shengjing Hospital, Sichuan Cancer Hospital and Research Institute, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Third Military Medical University, Tianjin Medical University, West China Second University Hospital, Women Hospital, School of Medicine, Zhejiang University, Xiangya Hospital of Central South University, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response	Proportion of patients with no tumor cells on postoperative pathology and negative lymph node metastasis	At the end of the patient's treatment, up to 2 years.
Secondary	The negative conversion of HPV	Proportion of patients with known HPV infection at screening who are HPV-negative after treatment	At the end of treatment, up to 2 years.
Secondary	Pregnancy rate	the ratio of the number of women with a successful pregnancy to the total number of women who attempted to become pregnan	Until the end of the 5-year follow-up period, up to 7 years.
Secondary	Miscarriage rate	the ratio of miscarriage events that occur during pregnancy in women who are pregnant	Until the end of the 5-year follow-up period, up to 7 years.
Secondary	Live birth rate	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	Until the end of the 5-year follow-up period, up to 7 years.
Secondary	Preterm birth rate	The preterm birth rate is the proportion of babies born at less than 37 weeks of gestation	Until the end of the 5-year follow-up period, up to 7 years.
Secondary	Adverse Event	Adverse Effects of immunotherapy and chemotherapy	during the treatment, up to 5 years.
Secondary	Surgical complications	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.	During and after the surgery, up to 2 years.
Secondary	Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Function Score	Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Function Score	From enrollment to the end of the 5-year follow-up period. 5 years.
Secondary	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.	From enrollment to the end of the 5-year follow-up period. 5 years.
Secondary	Event-free survival (EFS)	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 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.	Until the end of the 5-year follow-up period, up to 7 years.
Secondary	Overall survival (OS)	the time from the start of enrollment to death from any cause	Until the end of the 5-year follow-up period, up to 7 years.