2024-517241-13-00已完成2 期
Evaluation of treatment PERSOnalization based on its therapeutic monitoring in patients with metastatic colorectal cancer treated with regorafenib
Centre Hospitalier Universitaire De Rennes, Centre Hospitalier Universitaire De Rennes8 个研究点 分布在 1 个国家目标入组 110 人开始时间: 2024年9月26日最近更新:
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 8
- 主要终点
- The primary endpoint is the overall survival defined as the time from inclusion to death from any cause. Two groups of patients will be defined a posteriori based on trough concentration of regorafenib and active metabolites: • Group with "optimal exposure": Csum on C1 and/or Csum on C2 within the range [2.5 – 5.5 mg/L]. • Group with "non optimal exposure": Csum on C1 and Csum on C2 outside the range [2.5 – 5.5 mg/L].
研究概览
简要总结
The primary objective of the trial is to determine whether "optimal exposure" to regorafenib based on plasma concentration of the drug and its metabolites can improve overall survival in mCRC patients.
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female patients ≥ 18 years-old at time of Informed Consent Form (ICF) signature
- •Women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy
- •Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior randomization
- •Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
- •Patients affiliated to the Social Security System
- •Signed and dated informed consent
- •Patients must have a histologically proven metastatic colorectal cancer
- •Patients who have previously been treated with standard therapy including a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF (bevacizumab or aflibercept) and an anti-EGFR (cetuximab or panitumumab) for patients who had a RAS wild-type tumor.
- •In mCRC with MSI-H, the patient must have received immunotherapy. For mCRC with BRAF mutation, the patient should have received a BRAF inhibitor if eligible.
- •ECOG PS = 0 or 1
- •Imaging target greater than one cm must be visible on CT
- •Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the pre-therapeutic check-up performed within 7 days before regorafenib initiation
- •INR/PTT ≤1.5 x ULN
- •Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. For patient treated with VKA close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
排除标准
- •Prior treatment with regorafenib, and with any prior antiangiogenic inhibitor except bevacizumab
- •Breastfeeding
- •Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg despite optimal medical management)
- •Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), within 6 months before the start of study medication
- •Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
- •Myocardial infarction less than 6 months before the start of study medication
- •Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v 5.0 within 4 weeks prior to the start of study medication
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication
- •Non-healing wound, ulcer or bone fracture
- •Unresolved toxicity higher than Grade 1, NCI-CTCAE v 5.0, attributed to any prior therapy/procedure excluding alopecia, anemia, hypothyroidism and oxaliplatin induced neuropathy
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Hypersensitivity to the active substance or to any of the excipients
- •Adults legally protected (judicial protection, guardianship or supervision), person deprived of their liberty
- •Systemic cancer therapy with unfinished washout (in general 3 weeks except for example for capecitabin which has a 1 week washout)
- •Concomitant treatment with a cytochrome P450 3A4 (CYP3A4) inducer or inhibitor or UGT1A9 inhibitor
- •Patients unable to swallow oral medication
- •Digestive obstruction, chronic inflammatory bowel disease or any malabsorption condition
- •Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria])
- •Ongoing uncontrolled infection (viral, bacterial or fungal)
- •Known history of human immunodeficiency virus (HIV) infection, active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy
结局指标
主要结局
The primary endpoint is the overall survival defined as the time from inclusion to death from any cause. Two groups of patients will be defined a posteriori based on trough concentration of regorafenib and active metabolites: • Group with "optimal exposure": Csum on C1 and/or Csum on C2 within the range [2.5 – 5.5 mg/L]. • Group with "non optimal exposure": Csum on C1 and Csum on C2 outside the range [2.5 – 5.5 mg/L].
The primary endpoint is the overall survival defined as the time from inclusion to death from any cause. Two groups of patients will be defined a posteriori based on trough concentration of regorafenib and active metabolites: • Group with "optimal exposure": Csum on C1 and/or Csum on C2 within the range [2.5 – 5.5 mg/L]. • Group with "non optimal exposure": Csum on C1 and Csum on C2 outside the range [2.5 – 5.5 mg/L].
次要结局
- 10-month survival rate (defined as the percentage of patients alive 10 months after inclusion)
- Objective response Rate (ORR) according to RECIST 1.1 and assessed by the investigators. ORR is be defined as the rate of patients with complete or partial response
- Disease Control Rate (DCR) according to RECIST 1.1 and assessed by the investigators. DCR is defined as the rate of patients with complete response, partial response or stable disease
- Progression-free survival (PFS) according to RECIST 1.1, assessed by the investigators. PFS is defined as the time from inclusion to date of first observed disease progression (radiological or clinical) or death due to any cause, if death occurs before progression is documented. The actual date that the tumor scan was performed will be used for this calculation. PFS for patients without disease progression or death at the time of analysis will be censored at the last date of tumor evaluation
- Percentage of patients with significant toxicities (≥ grade 3). AEs will be assessed from inclusion to 28 day after the discontinuation of the study drug and classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
- Percentage of patients with “optimal exposure” – i.e. with Csum at D15 within the range [2.5 – 5.5 mg/L]) – at cycle 1 and cycle 2
- Overall survival for the half of patients with a low ratio of plasma concentration of M-2 C2/C1 compared to the overall survival for the half of patients with a high ratio of plasma concentration of M-2 C2/C1
- Genetic polymorphisms in gene involved in regorafenib metabolism and plasma concentrations of regorafenib and its metabolites
- Body composition will be determined on Computerized Tomography scan (CT-scan) imaging done at baseline and for tumor response evaluation during treatment.
- Plasma metabolomics biomarkers (quantitative and qualitative composition) within 7 days before Day 1, at D15C1, D15C2 and end of treatment
研究者
Astrid LIEVRE
Scientific
Centre Hospitalier Universitaire De Rennes
研究点 (8)
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