FOLFOX + Immunotherapy With Intrahepatic Administration of Oxaliplatin for Patients With Multiple Non-resectable Liver Metastasis From Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Disease-free Survival at 3 years
研究概览
简要总结
In this trial chemotherapy regimen FOLFOX with intrahepatic administration of oxaliplatin is combined with immunotherapy (nivolumab and ipilimumab) for the group of patients with multiple liver metastasis from colorectal cancer. Investigators hope to increase the disease-free survival after 3 years from 10 % to 30%.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent
- •Age: 18 - 79 years
- •Performance status 0-
- •Histologically documented colorectal cancer (In case primary tumor has not yet been removed, it should be possible to be removed by surgery)
- •Tumor is immunohistochemically microsatellite stable (MSS)
- •More than 5 liver metastasis, not eligible for liver resection or radiofrequency ablation (RFA)
- •Presence of liver metastasis documented on CT-scan with no documented extrahepatic disease except from primary tumor in situ.
- •Measurable disease according to RECIST 1.1
- •Involved liver tissue under 70 %
- •Perfusion of liver metastasis possible via a. hepatica
- •ANC >= 1,5 x 10¨9/ml og Platelets >= 100 x 10¨9/ml ,
- •Estimated creatinine clearance >= 60 ml/min
- •INR < 1,4 and bilirubin <= 1,5 x ULN
排除标准
- •Current or prior second malignancy within 5 years, except from basal cell carcinoma or carcinoma in situ cervix uteri.
- •Severe medical condition, such as severe cardiac disease or AMI within 1 year
- •Uncontrolled infection.
- •Patients positive for HIV, HBV-sAG or HCV antibody
- •Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of ipilimumab, nivolumab. The following are exceptions to this criterion:
- •Intranasal, inhaled, or topical steroids; or local steroid injections (e.g. intra-articular injection)
- •Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
- •Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
- •Patients requiring treatment with oral prednisolon of dose > 10 mg daily
- •Previous severe, unexpected reaction related to treatment with fluoropyrimidine.
- •Previous treatment with oxaliplatin or immunotherapy
- •Neuropathy that is contraindicated for treatment with oxaliplatin
- •Pregnant or breastfeeding women. Women with childbearing potential (WOCBP) should have a negative pregnancy test and agree to use highly effective method(s) of contraception during treatment and 6 months thereafter.
- •Men who are sexually active with WOCBP who do not agree to use highly effective method(s) of contraception during treatment and 7 months after immunotherapy or 6 months after chemotherapy (which period is the longest)
- •Patients who, for linguistic, intellectual or cultural reasons, will not be able to fully understand the concept of treatment and respond to any. complications.
研究组 & 干预措施
FOLFOX + Immunotherapy
8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6)
Immunotherapy:
Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations)
干预措施: Oxaliplatin (Drug)
FOLFOX + Immunotherapy
8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6)
Immunotherapy:
Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations)
干预措施: 5-Fluorouracil (Drug)
FOLFOX + Immunotherapy
8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6)
Immunotherapy:
Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations)
干预措施: Leucovorin (Drug)
FOLFOX + Immunotherapy
8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6)
Immunotherapy:
Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations)
干预措施: Nivolumab (Drug)
FOLFOX + Immunotherapy
8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6)
Immunotherapy:
Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations)
干预措施: Ipilimumab (Device)
结局指标
主要结局
Disease-free Survival at 3 years
时间窗: 3 years from start of treatment within the trial
Proportion of patients without signs of disease 3 years after treatment start
次要结局
- Safety and tolerability of the treatment(During the 16 weeks of treatment and 100 days thereafter (up to 31 weeks))
- Patients becoming eligible for resection of liver metastasis(Evaluation of resectability after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks))
- Objective response rate(Evaluation by CT-scan after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks))
- Overall survival(Survival follow-up is planned for at least 3 years from treatment start)
- Progression free survival(Evaluation by CT-scan after 8 cycles of treatment each cycle is 14 days) and every 3 months thereafter until progression (max 3 years))
研究者
Dorte Nielsen
Professor Dorte Nielsen, MD, PhD, DMSc
Herlev Hospital