A Single-Center, Single-Arm, Phase II Study of Perioperative Adebrelimab Combined With Neoadjuvant Paclitaxel and Platinum Chemotherapy in Locally Advanced Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response (pCR) Rate
研究概览
简要总结
This prospective, single-center, single-arm, phase II study will evaluate perioperative adebrelimab in patients with locally advanced cervical cancer. Approximately 35 participants will receive three 3-week cycles of neoadjuvant adebrelimab in combination with paclitaxel and cisplatin or carboplatin. Participants without disease progression who are considered resectable will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last cycle of neoadjuvant treatment.
Postoperative treatment will be risk-adapted according to pathological risk factors. Participants with high-risk pathological factors will discontinue protocol treatment and receive standard concurrent chemoradiotherapy. Participants with intermediate-risk factors will receive guideline-recommended pelvic radiotherapy plus adebrelimab maintenance, whereas low-risk participants will receive adebrelimab maintenance. Adebrelimab maintenance will be administered every 3 weeks for up to 1 year and may be discontinued early after two consecutive negative circulating tumor HPV DNA tests at least 3 months apart.
The primary endpoint is the pathologic complete response rate. Secondary endpoints include objective response rate, disease control rate, disease-free survival, 2-year disease-free survival rate, overall survival, duration of response, quality of life, and safety. Dynamic circulating tumor HPV DNA will also be explored as a biomarker of treatment response and postoperative recurrence risk.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 75 years.
- •Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix; FIGO 2018 stage IB3 or IIA2, or carefully selected stage IIB or IIIC1r disease following multidisciplinary team evaluation, with a maximum primary tumor diameter ≥4 cm. For participants with stage IIB or IIIC1r disease, PET/CT or an equivalent staging examination must exclude para-aortic lymph node metastasis and distant metastasis, and definitive concurrent chemoradiotherapy must remain feasible if neoadjuvant treatment is ineffective.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Able to provide adequate tumor tissue for biomarker testing, defined as at least 18 qualified tissue sections.
- •No prior surgery for cervical cancer, except staging procedures, and no prior radiotherapy, chemotherapy, systemic anticancer therapy, investigational therapy, or immunotherapy for cervical cancer.
- •At least one measurable lesion according to RECIST version 1.1, defined as a tumor lesion with a longest diameter ≥10 mm on CT or a lymph node with a short-axis diameter ≥15 mm on CT.
- •Estimated life expectancy ≥6 months.
- •No primary or metastatic central nervous system disease.
- •Adequate major organ function, meeting all of the following criteria:
- •No blood or blood-product transfusion within 14 days before assessment;
- •Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;
- •Platelet count ≥80 × 10⁹/L;
- •Hemoglobin ≥9 g/dL;
- •Total bilirubin <1.5 × upper limit of normal (ULN);
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN;
- •Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula.
- •Positive for high-risk human papillomavirus (HPV) DNA.
- •Written informed consent provided and willingness to comply with protocol-required follow-up.
排除标准
- •Considered unsuitable for participation in the study by the investigator.
- •Known hypersensitivity or allergy to any study drug.
- •Any active, known, or suspected autoimmune disease, including but not limited to interstitial pneumonitis, uveitis, enteritis, hepatitis, arthritis, nephritis, hypophysitis, hyperthyroidism, or hypothyroidism; vitiligo; or asthma requiring medical intervention with bronchodilators.
- •Congenital or acquired immunodeficiency, including HIV infection, hepatitis B, or hepatitis C.
- •Prior treatment with PD-1 and/or PD-L1 inhibitors, CTLA-4 antibodies, or other agents targeting immune-regulatory receptors.
- •Current use of immunosuppressive agents. Patients in a stable condition who do not require systemic immunosuppressive therapy may be eligible.
- •Long-standing unhealed wounds or fractures; major surgery, severe traumatic injury, fracture, or ulcer within 4 weeks before initiation of study treatment.
- •Poorly controlled cardiac symptoms or cardiovascular disease, including New York Heart Association (NYHA) class III-IV heart failure or left ventricular ejection fraction (LVEF) <50%; abnormal coagulation function defined as INR >1.5 or APTT >1.5 × ULN with a bleeding tendency; or an arterial or venous thromboembolic event within 6 months before the first dose of study treatment.
- •Symptomatic ascites, pleural effusion, or pericardial effusion requiring therapeutic puncture or drainage. Patients whose pleural or pericardial effusion remains stable for at least 2 weeks after drainage before the first dose of study treatment may be eligible.
- •Central nervous system metastases.
- •History of another malignancy, except for cured basal cell carcinoma of the skin or cervical carcinoma in situ.
- •Pregnant or breastfeeding women.
- •History of psychotropic drug abuse with inability to discontinue such use, or presence of a psychiatric disorder.
研究组 & 干预措施
Adebrelimab Plus Paclitaxel and Platinum-Based Chemotherapy
Participants will receive three cycles of neoadjuvant adebrelimab (1200 mg intravenously every 3 weeks) plus paclitaxel (175 mg/m² intravenously every 3 weeks) and cisplatin (70-75 mg/m² intravenously every 3 weeks) or carboplatin (AUC 5 intravenously every 3 weeks). Participants considered suitable for R0 resection will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last neoadjuvant cycle. Postoperative management will be risk-adapted. Eligible intermediate- and low-risk participants will receive adebrelimab maintenance every 3 weeks for up to 1 year, with early discontinuation permitted after two consecutive negative ctHPV DNA tests at least 3 months apart
干预措施: Carboplatin (AUC 5) (Drug)
Adebrelimab Plus Paclitaxel and Platinum-Based Chemotherapy
Participants will receive three cycles of neoadjuvant adebrelimab (1200 mg intravenously every 3 weeks) plus paclitaxel (175 mg/m² intravenously every 3 weeks) and cisplatin (70-75 mg/m² intravenously every 3 weeks) or carboplatin (AUC 5 intravenously every 3 weeks). Participants considered suitable for R0 resection will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last neoadjuvant cycle. Postoperative management will be risk-adapted. Eligible intermediate- and low-risk participants will receive adebrelimab maintenance every 3 weeks for up to 1 year, with early discontinuation permitted after two consecutive negative ctHPV DNA tests at least 3 months apart
干预措施: Paclitaxel (Drug)
Adebrelimab Plus Paclitaxel and Platinum-Based Chemotherapy
Participants will receive three cycles of neoadjuvant adebrelimab (1200 mg intravenously every 3 weeks) plus paclitaxel (175 mg/m² intravenously every 3 weeks) and cisplatin (70-75 mg/m² intravenously every 3 weeks) or carboplatin (AUC 5 intravenously every 3 weeks). Participants considered suitable for R0 resection will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last neoadjuvant cycle. Postoperative management will be risk-adapted. Eligible intermediate- and low-risk participants will receive adebrelimab maintenance every 3 weeks for up to 1 year, with early discontinuation permitted after two consecutive negative ctHPV DNA tests at least 3 months apart
干预措施: Cisplatin (Drug)
Adebrelimab Plus Paclitaxel and Platinum-Based Chemotherapy
Participants will receive three cycles of neoadjuvant adebrelimab (1200 mg intravenously every 3 weeks) plus paclitaxel (175 mg/m² intravenously every 3 weeks) and cisplatin (70-75 mg/m² intravenously every 3 weeks) or carboplatin (AUC 5 intravenously every 3 weeks). Participants considered suitable for R0 resection will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last neoadjuvant cycle. Postoperative management will be risk-adapted. Eligible intermediate- and low-risk participants will receive adebrelimab maintenance every 3 weeks for up to 1 year, with early discontinuation permitted after two consecutive negative ctHPV DNA tests at least 3 months apart
干预措施: Adebrelimab (Drug)
结局指标
主要结局
Pathologic Complete Response (pCR) Rate
时间窗: At definitive surgery, planned 28-42 days after completion of the third cycle of neoadjuvant treatment (approximately 10-12 weeks after initiation of treatment)
The proportion of participants achieving pathologic complete response following neoadjuvant treatment. pCR is defined as no residual invasive carcinoma in the cervical primary tumor and no metastatic carcinoma in any resected regional lymph node, with ypT0/is ypN0 used as the operational definition. The primary analysis denominator will include all participants who receive at least one dose of study treatment. Participants who do not undergo surgery, experience disease progression, withdraw, die, or have missing primary endpoint data will be considered not to have achieved pCR.
次要结局
- ORTC QLQ-C30 Scores Outcome(Baseline and at the end of each 21-day treatment cycle during study treatment, through completion of study treatment, up to 1 year)
- Objective Response Rate (ORR)(From baseline to preoperative tumor assessment after completion of three cycles of neoadjuvant treatment, approximately 9 weeks)
- Disease Control Rate (DCR)(From baseline to preoperative tumor assessment after completion of three cycles of neoadjuvant treatment, approximately 9 weeks)
- Disease-Free Survival (DFS)(From definitive surgery to disease recurrence, death, or last disease-free follow-up, assessed through December 31, 2029)
- Two-Year Disease-Free Survival Rate(2 years after definitive surgery)
- Overall Survival (OS)(From first study treatment to death or last known alive, assessed through December 31, 2029)
- Duration of Response (DOR)(From first documented CR or PR to disease progression or death, assessed through December 31, 2029)
- Incidence of Adverse Events(From the first dose of study treatment through 90 days after the last dose or initiation of a new anticancer treatment, whichever occurs first)
- EORTC QLQ-CX24 Outcome(Baseline and at the end of each 21-day treatment cycle during study treatment, through completion of study treatment, up to 1 year)