Phase I/IIa, Single-Arm, Open Study of Apatinib and MASCT in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Incidence of treatment-related adverse events
研究概览
简要总结
The study is aimed to evaluate the efficacy and safety of Apatinib and MASCT in patients with advanced solid tumors.
详细描述
Angiogenesis is a hallmark of cancer, together with vascular endothelial growth factor (VEGF) as one of the most important angiogenic drivers. Inhibitors targeting the VEGF/VEGFR-pathway have shown beneficial effects in many cancer patients, but they are transient and followed by fast regrowth. Similarly, the effectiveness of tumor immunotherapies has been limited by tumor-mediated escape mechanisms and immune suppression. By combining the two strategies, antiangiogenic immunotherapy offers the possibility to more vigorously inhibit tumor angiogenesis and promote an enduring immune-stimulatory milieu that leads to prolonged survival benefits in cancer patients.
Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). Apatinib has been demonstrated as monotherapy prolongs OS in patients with gastric or gastroesophageal junction adenocarcinoma after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse events.
Multiple antigens specific cellular therapy (MASCT) is a new immunotherapy that dendritic cells(DC) was induced from autologous peripheral blood. The DC can then be loaded with 17 antigens and re-infused. In vitro, antigen-pulsed DC can stimulate autologous T-cell proliferation and induction of autologous specific cytotoxic T-cells(CTL)，similarly re-infused. The previous research data showed that MASCT had the modest overall response and less adverse effects for Hepatocellular Carcinoma patients.
The study is aimed to evaluate the efficacy and safety of Apatinib and MASCT in patients with advanced solid tumors.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically-confirmed, advanced (unresectable) solid tumors who have progressed on standard therapy.
- •With written informed consent signed voluntarily by patients themselves.
- •The time of between Patients enrollment and the end of other anti-tumors therapies≤1 month
- •Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
- •At least one measurable lesion as defined by RECIST criteria 1.1 for solid tumors.
- •Life expectancy ≥6 months.
- •With normal cardiopulmonary function.
- •Patients have adequate organ function as defined by the following criteria:
- •Hemoglobin (HGB) ≥85g/L
- •Absolute neutrophil count (ANC) ≥1.0×109/L
- •White blood cell (WBC) ≥3.0×109/L
- •Platelet count ≥50×109/L
- •Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) of ≤2.5 upper normal limitation (UNL) or ≤5 UNL in case of liver metastasis
- •Alkaline phosphatase (ALP)≤2.5 UNL
- •Total bilirubin (TBil) of ≤1.5 UNL
- •Blood urea nitrogen (BUN) and Creatinine (Cr) of≤1.5 UNL
- •Albumin (ALB) ≥30g/L
排除标准
- •Pregnant or expecting to pregnant
- •Participated in other clinical trials before screening except of observational study.
- •Known allergic history of sodium citrate drugs.
- •Known history of organ transplant, including autologous bone marrow transplantation and peripheral stem cell transplantation.
- •Known active brain metastases as determined by CT or MRI evaluation.
- •The use of immunosuppressive drugs with current or 14 days before enrollment.
- •Know the period of systemic and continuous use of immunomodulatory agents (such as interferon, thymosin, traditional Chinese medicine) within 6 months.
- •Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including any other antibody or drug specifically targeting T-cell co-stimulation).
- •Known history of primary immunodeficiency diseases.
- •Known history of tuberculosis.
- •Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •Patients with serious infection, hepatopathy, nephropathy, respiratory disease, cardiovascular disease or incontrollable diabetes, etc.
- •Patients have other malignant tumors within 5 years,excluding melanoma and carcinoma in situ of cervix.
- •Treatment with any anti-tumors agent within 28days of first administration of study treatment.
研究组 & 干预措施
Apatinib+MASCT
Apatinib+Multiple Antigens Specific Cellular Therapy(MASCT) in patients with advanced solid tumors,excluding T cell lymphoma
干预措施: Apatinib (Drug)
Apatinib+MASCT
Apatinib+Multiple Antigens Specific Cellular Therapy(MASCT) in patients with advanced solid tumors,excluding T cell lymphoma
干预措施: MASCT (Biological)
结局指标
主要结局
Incidence of treatment-related adverse events
时间窗: up to 2 years
The incidence of treatment-related adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
次要结局
- Overall Survival (OS)(From enrollment to death of patients. Estimated about 1 year.)
- Objective Response Rate (ORR)(up to 2 years)
- Progression-Free Survival (PFS)(From enrollment to progression of disease. Estimated about 6 months.)
- Disease Control Rate (DCR)(up to 2 years)