A Prospective, Randomized, Controlled Phase II Trial of Regorafenib Alone or in Combination With High/Low-dose Radiotherapy Plus Toripalimab as Third-line Treatment in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- OS
研究概览
简要总结
The study compares the efficacy and safety of regorafenib alone or in combination with stereotactic ablative radiotherapy (SABR) and low-dose radiotherapy (LDRT) plus toripalimab in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). Patients are randomly assigned (1:1) into the control arm and the experimental arm. Control arm: a total of 45 patients will receive regorafenib monotherapy. Experimental arm: a total of 45 patients will first receive 1 cycle of regorafenib and toripalimab followed by SABR/LDRT radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy. The objective response rate (ORR), survival benefits, and adverse effects will be analyzed.
详细描述
Control arm: regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.
Experimental arm: regorafenib is administered 80 mg once daily on days 1-21 of each 28 days cycle with intravenous toripalimab 240 mg every 3 weeks. Radiotherapy regimes include 4-8 fractions of 8-12Gy via SABR and up to 1-10Gy at 0.5-2Gy/fraction via LDRT.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old
- •An Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Life expectancy of at least 3 months
- •Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum
- •At least two evaluable metastatic lesions for SABR and LDRT according to RECIST 1.1
- •Progressed on or after the standard first-and second-line therapies or stopped standard therapy because of unacceptable toxic effects
- •Previous radiotherapy completed at least 4 weeks before randomization
- •Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN
- •Sign the informed consent and have good compliance
排除标准
- •History of previous treatment with regorafenib and ICIs such as anti-PD-1 or anti-PD-L1 mAbs
- •Current severe cardiovascular diseases such as unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication
- •Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment
- •Active autoimmune diseases and immunodeficiencies, known history of organ transplantation, or systematic use of immunosuppressive agents
- •Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: HBsAg positive or HBV DNA positive, anti-HCV antibody testing positive and confirmatory HCV RNA positive
- •Positive human immunodeficiency virus (HIV) infection, active syphilis infection, or active pulmonary tuberculosis infection
- •Severe infections requiring systemic antibiotics, antifungal or antiviral therapy
- •Uncontrollable pleural effusion, pericardial effusion, or ascites
- •Other malignancies within 5 years before recruitment, except for non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ, or breast cancer in situ that had been effectively treated.
- •Known history of severe neurological or mental illness such as schizophrenia, dementia, or epilepsy
- •Known history of allergy to any component involved in this study.
- •Pregnancy or breast-feeding women
研究组 & 干预措施
monotherapy
a total of 54 patients will receive regorafenib monotherapy.
干预措施: Regorafenib (Drug)
combination therapies
a total of 54 patients will first receive 1 cycle of regorafenib and toripalimab followed by hypofractionated/low-dose radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy.
干预措施: Toripalimab (Drug)
combination therapies
a total of 54 patients will first receive 1 cycle of regorafenib and toripalimab followed by hypofractionated/low-dose radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy.
干预措施: Radiotherapy (Radiation)
combination therapies
a total of 54 patients will first receive 1 cycle of regorafenib and toripalimab followed by hypofractionated/low-dose radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy.
干预措施: Regorafenib (Drug)
结局指标
主要结局
OS
时间窗: Up to 2 years
Defined as the time from initiation of treatment to death from any cause.
次要结局
- PFS(Up to 2 years)
- DCR(Up to 1 year)
- ORR(Up to 1 year)
- DoR(Up to 1 year)
- Adverse events(Up to 1 year)