Adjuvant Chemoradiotherapy Followed by Zimberelimab for Locally Advanced Cervical Cancer.

Phase 2

Not yet recruiting

• Conditions: Cervical Cancer
• Interventions: Drug: Zimberelimab; Drug: Platinum; Radiation: radiotherapy

• Registration Number: NCT06128460
• Lead Sponsor: Obstetrics & Gynecology Hospital of Fudan University

Brief Summary

Locally advanced cervical cancer (stage IB3, IIA2) patients with postoperative risk factors need better treatment. We initiated a clinical study to explore the effectiveness of adjuvant chemoradiotherapy followed by Zimberelimab for these patients.

Detailed Description

For cervical cancer, although clinical research on PD-1 monoclonal antibodies was launched relatively late, the research results so far show that PD-1 monoclonal antibodies combined with chemotherapy have a high clinical effectiveness and a relatively high efficacy in the treatment of advanced/recurrent cervical cancer. Good security. However, there is currently a lack of clinical evidence for the use of PD-1 monoclonal antibodies combined with chemoradiotherapy in the treatment of high-risk patients after cervical cancer surgery. Therefore, this study intends to explore the clinical efficacy of postoperative adjuvant radiochemotherapy followed by PD-1 monoclonal antibody in the treatment of high-risk patients with locally advanced (IB3, IIA2) cervical cancer after surgery, and provide a new solution for clinical treatment.

Study Timeline

• Status Verified: 2023-11
• Study First Submitted: 2023-11-06
• Study First Submitted QC: 2023-11-09
• Study First Posted: 2023-11-13
• Last Update Submitted: 2023-11-27
• Last Update Posted: 2023-11-30
• Study Start: 2023-12-01
• Primary Completion: 2025-12-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 24

Inclusion Criteria

• Histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma;
• According to FIGO2018 staging, patients with locally advanced cervical cancer (IB3, IIA2) who require concurrent radiotherapy and chemotherapy;
• Patients with radical surgery for cervical cancer;
• Female patients: 18-70 years old;
• ECOG physical condition score: 0~1 point;
• Subjects have not received previous immunotherapy;
• Expected survival ≥6 months;
• Women of reproductive age should agree to use contraceptives (such as Iuds, contraceptives, or condoms) during the study period and for 6 months after the study ends; Have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be a non-lactating patient;
• For adequate organ function as defined in the protocol, test samples must be collected within 7 days prior to initiation of the study therapy
• Subjects voluntarily joined the study, signed informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria

• Subjects have histological subtypes other than those permitted by inclusion criteria;
• Severe hypersensitivity to cepalizumab and/or any of its excipients (≥ grade 3);
• Participate in or have participated in other clinical trials within 4 weeks before enrollment;
• Have received or will receive inactivated vaccine within 30 days prior to the first study treatment;
• Received a combination of systemic immune stimulants, colony-stimulating factors, interferon, interleukin, and vaccine within 6 weeks or 5 half-lives (if shorter) prior to initial administration;
• Have been diagnosed with an immune deficiency or are receiving chronic systemic steroid therapy (doses greater than 10mg daily equivalent of prednisone) or any other form of immunosuppressive therapy within 7 days prior to the first dose;
• Have an active autoimmune disease in the past 2 years that requires systemic treatment (such as the use of disease-modulating drugs, corticosteroids, or immunosuppressive drugs);
• Have a history of (non-infectious) pneumonia requiring steroid treatment or have a current (non-infectious) pneumonia;
• An active infection requiring systematic treatment;
• Known history of HIV infection;
• A known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as detection of HCV RNA[qualitative]) infection;
• Known active tuberculosis (TB; Tuberculosis) medical history;
• Has received allogeneic tissue/solid organ transplantation;
• Suffering from central nervous system metastases such as brain metastases;
• Patients with uncontrolled chest and abdominal fluid;
• Patients with mobility disorders such as pathological fractures caused by tumor bone metastasis;
• Insufficient hematopoietic function of bone marrow;
• Abnormal liver;
• Abnormal kidney;
• Bleeding risk;
• Cardiovascular and cerebrovascular abnormalities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Concurrent themoradiotherapy Followed by Zimberelimab	radiotherapy	1. Radiotherapy: Intensity modulated conformal radiation therapy (IMRT) is used for external irradiation, and the pelvic target volume dose (PTV) is: 45-50 Gy/1.8Gy/25-28f; the stump margin is positive, and after the external irradiation is completed, Additional CT-guided three-dimensional conformal brachytherapy, HR-CTV: 24--30Gy/4-5f. 2. Concurrent chemotherapy: performed during external radiotherapy. Starting from the first week of radiochemotherapy, cisplatin 40 mg/m2 was given. Chemotherapy is given every 7 days, up to 5-6 times; 3. Zimberelimab injection: 240 mg/time, intravenous infusion, administered every 21 days, starting within four weeks after completing concurrent chemoradiotherapy, and maintained for 8 cycles
Concurrent themoradiotherapy Followed by Zimberelimab	Zimberelimab	1. Radiotherapy: Intensity modulated conformal radiation therapy (IMRT) is used for external irradiation, and the pelvic target volume dose (PTV) is: 45-50 Gy/1.8Gy/25-28f; the stump margin is positive, and after the external irradiation is completed, Additional CT-guided three-dimensional conformal brachytherapy, HR-CTV: 24--30Gy/4-5f. 2. Concurrent chemotherapy: performed during external radiotherapy. Starting from the first week of radiochemotherapy, cisplatin 40 mg/m2 was given. Chemotherapy is given every 7 days, up to 5-6 times; 3. Zimberelimab injection: 240 mg/time, intravenous infusion, administered every 21 days, starting within four weeks after completing concurrent chemoradiotherapy, and maintained for 8 cycles
Concurrent themoradiotherapy Followed by Zimberelimab	Platinum	1. Radiotherapy: Intensity modulated conformal radiation therapy (IMRT) is used for external irradiation, and the pelvic target volume dose (PTV) is: 45-50 Gy/1.8Gy/25-28f; the stump margin is positive, and after the external irradiation is completed, Additional CT-guided three-dimensional conformal brachytherapy, HR-CTV: 24--30Gy/4-5f. 2. Concurrent chemotherapy: performed during external radiotherapy. Starting from the first week of radiochemotherapy, cisplatin 40 mg/m2 was given. Chemotherapy is given every 7 days, up to 5-6 times; 3. Zimberelimab injection: 240 mg/time, intravenous infusion, administered every 21 days, starting within four weeks after completing concurrent chemoradiotherapy, and maintained for 8 cycles

Primary Outcome Measures

Name	Time	Method
changes in tumor-related biomarkers	3 years	changes of tumor- related biomarkers (T cell receptor library profile and peripheral blood ctDNA content analysis)

Secondary Outcome Measures

Name	Time	Method
OS	5 years	Overall Survival
DFS	2 years	Disease Free Survival
AE	3 years	Adverse event