An Open-labeled, Single-arm, Investigator-initiated Phase II Trial of Camrelizumab (Anti-PD-1 Antibody) in Combination With Apatinib and Eribulin in Patients With Advanced Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 46
- 试验地点
- 3
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This is a phase II, open-labeled, multi-centered,single-arm, Investigator-initiated clinical trial of camrelizumab (an anti-PD-1 antibody) in combination with apatinib (a VEGFR2 TKI) and eribulin mesylate in patients with advanced triple-negative breast cancer. We will enroll 46 subjects (Simons two stage design). This study aims to evaluate the efficacy and safety of camrelizumab combined with apatinib and eribulin in the treatment of advanced TNBC.
详细描述
This a phase II, open-labeled, multi-centered, single-arm, investigator-initiated clinical trial to assess the efficacy and safety of camrelizumab combination with apatinib and eribulin in female patients age of 18 to 70 with advanced TNBC, and previously treated with at least one line of systemic therapy in the advanced setting. Prior therapy (adjuvant/neoadjuvant/advanced) must have included an anthracycline and a taxane. The number of patients to be included is 46 patients (Simons two stage design). The primary objective is to assess the overall response rate (ORR). All enrolled patients will be treated with camrelizumab 200mg (iv. 3mg/kg for patient whose weight is below 50kg) on day 1 of each 21-day cycle, and apatinib 250mg daily (po, d1-d21), in combination with eribulin mesylate at 1.4 mg/m2 (iv.) on day 1 and day 8 of every 21-day cycle.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •The patients sign the written informed consent.
- •Women aged 18-
- •The pathologic diagnosis of unresectable recurrent or metastatic triple-negative breast cancer ［ER-negative(IHC<1%), PR-negative(IHC<1%), HER2-negative（IHC-/+ or IHC++ and FISH/CISH-）］. Patients with at least one measuring lesion that was conformed to RECIST v1.1 standard.
- •Prior therapy (adjuvant/neoadjuvant/advanced) must have included an anthracycline and a taxane in any combination or order and either in the early or metastatic disease setting unless contraindicated for a given patient.
- •The patient can swallow pills.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •With a life expectancy of at least 12 weeks.
- •The results of patient's blood tests are as follows:
- •Hb≥90g/L; • Plt≥100^9/L; • Serum albumin ≥3g/dL;• Neutrophils≥1.5^9/L; TSH≤ normal upper limit (ULN);• ALT and AST ≤1.5 ULN (liver metastases ≤3 ULN); • TBIL ≤ULN (total bilirubin ≤1.5 ULN in Gilbert's syndrome or liver metastasis subjects);• ALT and AST ≤1.5 ULN (liver metastases ≤3 ULN);• AKP≤ 2.5 ULN; • Renal function within 7 days before the first administration: serum creatinine ≤1.5 ULN or creatinine clearance ≥60mL/min
- •Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 6 months after the last dose of study treatment.
排除标准
- •The subjects had a central nervous system metastases with clinical symptoms.
- •Other clinical trials of drugs were used in the first four weeks before the first dose.
- •Subjects with severe allergic reactions to other monoclonal antibodies.
- •Received other anti-tumor treatments within 28 days before the first dose.
- •A heart condition or disease that is not well controlled.
- •Subjects with treatment history of anti-angiogenesis drugs, or immunotherapy (previous use of anti-PD-1/PD-L1 antibodies was allowed) or eribulin.
- •The subjects had any history of autoimmune disease or any use of systemic glucocorticoid or immunosuppressive medications.
- •Subjects had history of hypertension and poor control with antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
- •Urine routine indicated that urine protein ≥ ++, or the 24-hour urine protein quantity ≥ 1.0g.
- •Hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.).
- •Congenital or acquired immune deficiency (such as HIV infection);
- •Receive live vaccine within 4 weeks before or during the study period;
- •Patients who are allergic to or contraindicated to the experimental drugs.
研究组 & 干预措施
Camrelizumab +Apatinib+Eribulin
Camrelizumab 200mg(3mg/kg for patient whose weight is below 50kg) iv Q3W combination with Apatinib 250mg, po, daily (d1-d21)and Eribulin1.4mg/m2 iv d1, d8 Q3W
干预措施: Camrelizumab (Drug)
Camrelizumab +Apatinib+Eribulin
Camrelizumab 200mg(3mg/kg for patient whose weight is below 50kg) iv Q3W combination with Apatinib 250mg, po, daily (d1-d21)and Eribulin1.4mg/m2 iv d1, d8 Q3W
干预措施: Apatinib (Drug)
Camrelizumab +Apatinib+Eribulin
Camrelizumab 200mg(3mg/kg for patient whose weight is below 50kg) iv Q3W combination with Apatinib 250mg, po, daily (d1-d21)and Eribulin1.4mg/m2 iv d1, d8 Q3W
干预措施: Eribulin (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: from the first drug administration up to the first occurrence of progression or death (up to 24 months)
The propotion of subjects with CR or PR.
次要结局
- PFS(from the first drug administration up to the first occurrence of progression or death (up to 24 months))
- Disease Control Rate (DCR)(from the first drug administration up to the first occurrence of progression or death(up to 24 months))
- DOR(from the first drug administration up to the first occurrence of progression or death(up to 24 months))
- One year-OS rate(12 months after the first drug administration)
- Clinical benefit rate (CBR)(from the first drug administration up to the first occurrence of progression or death(up to 24 months))
- Incidence of Treatment-Emergent Adverse Events(from the first drug administration to within 90 days for the last dose)
- TTR(from the first drug administration up to one year)
- Frequencies of Biomarkers(pre-treatment, up to 24 months)
研究者
Jieqiong Liu, M.D., Ph.D.
Associate Professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University