Comparing neoadjuvant chemoimmunotherapy and concurrent chemoradiotherapy for locally advanced cervical cancer

Neoadjuvant Chemoimmunotherapy Combined With Surgery Versus Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer: a Multicenter Randomized Controlled Clinical Trial

This study is testing whether a new treatment combining chemoimmunotherapy and surgery can help people with locally advanced cervical cancer do better than the standard treatment of chemo and radiation.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 440 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: pembrolizumab, chemotherapy, prednisone, immunotherapy, radiation
• Locations: 12 sites (Hefei, Anhui and 11 other locations)
• Trial ID: NCT06288373 on ClinicalTrials.gov

What this trial studies

This clinical trial is a prospective, open-label, randomized controlled study that aims to evaluate the effectiveness of neoadjuvant chemoimmunotherapy combined with surgery versus the standard concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical cancer (LACC). Patients with PD-L1-positive tumors will be randomly assigned to receive either treatment approach. The study seeks to address the limitations of current therapies and improve patient outcomes, particularly focusing on disease-free survival and quality of life. It involves multiple centers across China and aims to provide robust data on the efficacy of the new treatment regimen.

Who should consider this trial

Good fit: Ideal candidates for this study are patients aged 18 to 70 with locally advanced cervical cancer (FIGO stage IB3, IIA2, or IIB) and positive PD-L1 expression.

Not a fit: Patients with early-stage cervical cancer or those who do not express PD-L1 may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved survival rates and quality of life for patients with locally advanced cervical cancer.

How similar studies have performed: Previous studies have shown promising results with neoadjuvant immunotherapy in advanced cervical cancer, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Locally advanced (2018 FIGO staged IB3, IIA2 and IIB（tumor size\> 4cm) ) cervical cancer，staging determined by two physicians of associate seniority or higher after gynecologic examination and imaging evaluation);
2. At least one measurable lesion at baseline according to RECIST 1.1 criteria, with lesion size based primarily on magnetic resonance imaging;
3. Pathologically confirmed diagnosis of cervical cancer, including cervical squamous cell carcinoma, adenocarcinoma (common type), and adenosquamous carcinoma;
4. Positive PD-L1 expression, Combined Positive Score (CPS) ≥1;
5. Patient age ≥18 years and ≤70 years;
6. ECOG score ≤1;
7. Laboratory tests: WBC (white blood cell count) ≥ 3.5×109/L, NEU (neutrophil count) ≥ 1.5×109/L, PLT (platelet count) ≥ 100×109/L, total bilirubin ≤ 1.5 times the upper limit of normal, ALT (alanine aminotransferase) and AST (aspartate aminotransferase) ≤ 1.5 times the upper limit of normal, serum creatinine (BUN) ≤ 1.5 times the upper limit of normal or creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula, the Chronic Kidney Disease Epidemiology Collaboration equation, or the Modification of Diet in Renal Disease equation);
8. Be willing to follow up and good compliance;
9. Be willing to sign the informed consent, including compliance with the requirements and restrictions listed in the informed consent and program；
10. Agree to use effective contraception measures during the trial period and for 5 months after the last dose of pembrolizumab or 6 months after chemotherapy (whichever is longer).

Exclusion Criteria:

1. Any active autoimmune disease or history of autoimmune disease requiring systemic treatment, including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring bronchodilator intervention;
2. 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;
3. Has a history of human immunodeficiency virus (HIV) infection, active hepatitis B (HBV-DNA ≥ 2000 IU/mL or 104 copies/mL), and hepatitis C (HCV antibody positive, and HCV-RNA above the lower limit of detection of the assay);
4. Receipt of immunosuppressive medications or systemic corticosteroid therapy for immunosuppression (\>10 mg/day prednisone or equivalent) within 2 weeks prior to study dosing;
5. Diagnosed with another primary malignancy within 5 years prior to the first use of the investigational drug;
6. Received other investigational drugs/treatments or participated in another clinical trial within 4 weeks prior to randomization. Participation in observational and non-interventional clinical trials is allowed;
7. Pregnant or breastfeeding female patients;
8. 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; cerebral vascular accidents or brain disorders within ≤ 6 months prior to study drug administration, or individuals 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 development of an active infection requiring systemic anti-infective therapy within 14 days prior to the first dose of study drug;
9. Treatment with a live or attenuated vaccine administered within 4 weeks prior to the first dose of study drug; inactivated seasonal influenza virus vaccine is permitted;
10. Patients with a prior allogeneic bone marrow or solid organ transplant;
11. Drug and/or alcohol abuse;
12. Patients who, in the opinion of the investigator, are unlikely to comply with the procedures, restrictions, and requirements of the study may not be enrolled in the study.

Where this trial is running

Hefei, Anhui and 11 other locations

• Anhui Provincial Cancer Hospital — Hefei, Anhui, China (Recruiting)
• Beiing Friendship Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• The First Affiliated Hospital (Southwest Hospital), Army Medical University (Third Military Medical University) — Chongqing, Chongqing Municipality, China (Recruiting)
• Gansu Provincial Maternity and Child-care Hospital — Lanzhou, Gansu, China (Recruiting)
• The Affiliated Tumor Hospital of Guangxi Medical University — Nanning, Guangxi, China (Recruiting)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Xiangya Hospital, Central South University — Changsha, Hunan, China (Recruiting)
• Shengjing Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Second People's Hospital of Sichuan (Sichuan Cancer Hospital) — Chengdu, Sichuan, China (Recruiting)
• Tianjin Medical University General Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• Women's Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Kezhen Li

Conditions Cervical Cancer; Locally Advanced Cervical Cancer; Concurrent Chemoradiotherapy; Neoadjuvant Chemoimmunotherapy