Randomized Phase II Study to Evaluate Induction Nivolumab-Ipilimumab, Followed by Nivolumab With Chemoradiotherapy Versus Chemoradiotherapy for Advanced Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 14
- 主要终点
- 3-year progression-free survival
研究概览
简要总结
A total of 112 patients with locally advanced cervical cancer will be randomized 1:1 to standard therapy with cisplatin-based chemoradiation or nivolumab-ipilimumab induction followed by cisplatin-based chemoradiation. The primary outcome will be 3-year disease-free survival.
详细描述
Patients with adenocarcinoma or squamous cell carcinoma of the cervix, FIGO Stage IB2-IB3 node positive or Stage IIB-IVA will be randomized to conventional cisplatin-based chemo-radiation or to 4 cycles of induction immunotherapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks, followed by cisplatin chemo-radiation with concurrent nivolumab 240mg every 2 weeks. Primary outcome will be 3-year progression-free survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female participants older than 18 years
- •Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO Stage IB2-IB3 node positive or Stage IIB-IVA
- •No prior chemotherapy, immune checkpoint inhibitors or radiotherapy for cervical cancer
- •WHO/ECOG performance status of 0-1
- •At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion at baseline.
排除标准
- •Diagnosis of small cell (neuroendocrine) histology cervical cancer
- •Intent to administer a fertility-sparing treatment regimen
- •Undergone a previous hysterectomy
- •Evidence of metastatic disease per RECIST 1.1 including lymph nodes ≥15 mm (short axis) above the L1 cephalad body or outside the planned radiation field.
- •History of allogeneic organ transplantation
- •Active or prior documented autoimmune or inflammatory disorders
- •Uncontrolled intercurrent illness
- •History of another primary malignancy and active primary immunodeficiency
- •Patients with active infection
- •Laboratory values that fall into:
- •WBC count (WBC) < 2000/μL ;
- •Neutrophil count < 1500/μL;
- •Platelet count < 100 x 103/μL;
- •Hemoglobin level < 9.0 g/dL;
- •Serum creatinine > 1.5 x upper limit of normal (ULN) unless creatinine clearance is
- •≥ 40 mL/min (measured or calculated using the Cockcroft-Gault formula);
- •Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): > 3.0 x ULN;
- •Total bilirubin > 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN);
- •Any positive test result for hepatitis B virus or hepatitis C virus that indicates the presence of the virus, for example, positive Hepatitis B surface antigen (HBsAg, Australia antigen) or Hepatitis C antibodies (anti- HCV) positive (unless the HCV-RNA is negative).
- •Participants with a condition requiring systemic treatment or with corticosteroids (>10 mg daily of a prednisone equivalent) or other immunosuppressive drugs within 14 days of initiating study treatment.
- •Pregnant or breastfeeding woman
研究组 & 干预措施
Standard Chemoradiation
Traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week or carboplatin AUC 2/week
干预措施: Chemoradiation (Radiation)
Immunotherapy
4 cycles of induction therapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks followed by traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week (or carboplatin AUC 2/week) with concurrent nivolumab 240mg every 2 weeks.
干预措施: Nivolumab 40 mg in 4 ml Injection (Drug)
Immunotherapy
4 cycles of induction therapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks followed by traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week (or carboplatin AUC 2/week) with concurrent nivolumab 240mg every 2 weeks.
干预措施: Ipilimumab 200 MG in 40 ML Injection (Drug)
Immunotherapy
4 cycles of induction therapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks followed by traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week (or carboplatin AUC 2/week) with concurrent nivolumab 240mg every 2 weeks.
干预措施: Chemoradiation (Radiation)
结局指标
主要结局
3-year progression-free survival
时间窗: 3 years
No evidence of disease recurrence/regrowth after 3 years of follow-up
次要结局
- Evaluate health related quality of life using supplemental cervical cancer module (EORTC CX24) to evaluate patients submitted to treatment with Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer.(Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).)
- Objective response rate(90 days after the end of chemoradiation)
- Response duration(Through study completion, an average of 3 year)
- To evaluate health related quality of life (HRQoL): defined as the change from baseline of disease-related symptoms and quality of life of patients undergoing treatment Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer(Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).)
- Treatment-related toxicity(Through study completion, an average of 3 year)
- 3-year overall survival(3 years)