Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma: a Phase II Study (SINAI)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- 12W-PFS
研究概览
简要总结
Splenomegaly is common in advanced pancreatic ductal adenocarcinoma (PDAC). The spleen is an important source of immune suppressive cells and phagocytic cells and may mediate the accumulation of liposomal drugs and immunosuppression. In this study, spleen irradiation (SI) will be added to standard chemotherapy.
详细描述
Splenomegaly is common in PDAC. Therefore, we design a phase II study to enroll metastatic PDAC patients who have failed prior gemcitabine-based therapy and have splenomegaly. With add-on SI to standard nal-IRI/FL therapy, we hypothesize that 1) splenic phagocytes and spleen volume will be reduced with attenuated entrapment of nal-IRI within spleen, 2) splenic source of immunosuppressive immune cells will be reduced with potential reconstitution of antitumor TME.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histologically or cytologically proved PDAC
- •metastatic PDAC
- •failed frontline gemcitabine-based chemotherapy and preparing for application of NHI-reimbursed nal-IRI/FL
- •splenomegaly: SV > 270 ml (estimated)
- •lymphopenia: < 1200/mm3
- •no previous radiotherapy, local therapy (eg. radiofrequency ablation, irreversible electroporation, etc.), cell therapy (autologous or allogenic) used for pancreatic cancer
- •presence of at least one measurable lesion outside spleen
- •age between 20 and 75 years at registration
- •ECOG performance status of 0 or 1
- •adequate major organ functions
- •limited progressive disease after prior nal-IRI/FL
- •prior treatment of nal-IRI/FL at least 4 doses
- •histologically or cytologically proven PDAC
- •metastatic PDAC before starting prior nal-IRI/FL
- •failed frontline gemcitabine-based chemotherapy before prior nal-IRI/FL
- •presence of at least one measurable lesion outside spleen
- •age between 20 and 75 years at registration
- •ECOG performance status of 0 or 1 or 2 after the chemotherapy phase
- •adequate major organ functions
排除标准
- •interstitial lung disease
- •presence of diarrhea ≥ CTCAE v.5.0 grade 2
- •concomitant systemic infection requiring treatment
- •clinically significant co-morbid medical conditions
- •prior organ allograft or allogeneic bone marrow transplantation
- •received systemic corticosteroids or immunosuppressants within 28 days before registration
- •known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
- •moderate or severe ascites, pleural effusion, or pericardial effusion requiring treatment
- •central nervous system metastasis
- •prior or concurrent malignancies within the last 3 years, with the exception of carcinoma in situ of the cervix, or basal type skin cancer
- •any major surgery within 4 weeks of study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury.
- •pregnant women or nursing mothers, or positive pregnancy tests
- •severe mental disorder
- •spleen metastasis or direct invasion
研究组 & 干预措施
Upfront SI
Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI
干预措施: nanoliposomal irinotecan (Drug)
Upfront SI
Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI
干预措施: spleen irradiation (Radiation)
Add-on SI
Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin
干预措施: nanoliposomal irinotecan (Drug)
Add-on SI
Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin
干预措施: spleen irradiation (Radiation)
结局指标
主要结局
12W-PFS
时间窗: 12 week
12-week PFS rate (%)
次要结局
未报告次要终点