LONsurf and G-CSF Use: Being On A Right Dose-intensity to Optimize Treatment Efficacy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 176
- 试验地点
- 22
- 主要终点
- Rate of patients free of trifluridine/tipiracil dose reduction or postponement of cycles of > 7 days at 6 months or at progression or death or stop of treatment for another cause than neutropenia if observed in 6 months.
研究概览
简要总结
Prospective cohort of patients treated with trifluridine/tipiracil, maximal sample size 250 patients. It is expected, that 89 patients will experience a grade 3-4 neutropenia and will be included in the phase II.
详细描述
Trifluridine/tipiracil has demonstrated its efficacy in patients with metastatic colorectal cancer (mCRC) resistant to standard drugs (fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and panitumumab or cetuximab in case of RAS wild-type tumors). This treatment has a marketing authorization.
Neutropenia is a classic complication of cytotoxic treatments. Febrile neutropenia are associated with a mortality rate of 9.5% and a hospitalization of 6 days in median. Recent meta-analyses have reported that the use of granulocyte-colony stimulating factor (GCSF) allows to maintain the dose-intensity of cytotoxic treatment and was associated with a better overall survival (OS).
There is currently no clear recommendation for the use of G-CSF with trifluridine/tipiracil.
Unpublished analyses that various clinical parameters may be associated with the risk of neutropenia: age ≥ 65 years, female sex, level of leukocytes at baseline, and time of initial diagnostic to randomization ≥ 36 months.These data are too preliminary to allow proposing a G-CSF primary prophylaxis in a defined subgroup of patients. However, a secondary prophylaxis based on the administration of G-CSF seems efficient, with a prescription from day 14 to day 18.
The aim of this phase II study is to assess the efficacy of the secondary prophylaxis with G-CSF in case of first episode of grade 3-4 neutropenia in the aim to maintain the optimal dose intensity.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent,
- •Patients willing and able to comply with protocol requirements,
- •Histologically proven colorectal adenocarcinoma,
- •Stage IV disease,
- •Have life expectancy of at least 6 months,
- •Previous chemotherapy regimens with each of the following agents: fluoropyrimidine, oxaliplatin, irinotecan, anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab, aflibercept), and anti-epidermal growth factor receptor (EGFR) therapy (cetuximab or panitumumab for tumors with wild-type RAS and/or BRAF wild type),
- •At least one measurable or evaluable lesion as assessed by computed tomography (CT)-scan or magnetic resonance imaging (MRI) according to RECIST v1.1,
- •Age ≥ 18 years,
- •ECOG PS 0-1,
- •Adequate hematologic function: neutrophils > 1.5 x 109 /L; platelets > 100 x 109 /L; hemoglobin ≥ 9 g/dL,
- •Calculated creatinine clearance ≥ 30 mL/min,
- •Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit normal ULN;
- •≤ 5 x ULN in case of liver metastasis), total bilirubin ≤ 1.5 x ULN (< 2 x ULN if hyperbilirubinemia is due to Gilbert's syndrome), albumin ≥ 25 g/L,
- •Baseline evaluations: clinical and blood evaluations no more than 14 days prior to inclusion and start of trifluridine/tipiracil, Tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 21 days prior to inclusion and start of trifluridine/tipiracil,
- •Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study (must have a negative pregnancy test within 7 days prior to enrollment) and during at least 6 months after the end of the last dose of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β-HCG) within 72 hours prior to starting trifluridine/tipiracil treatment. Breastfeeding is not allowed. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least 6 months after the end of the study treatment,
- •Registration with the French National Health Care System or PUMA (Protection Universelle MAladie).
排除标准
- •Medical history or evidence of CNS metastasis upon physical examination, unless adequately treated (e.g. non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, patients are stable without evidence of progression for at least 28 days prior to the first dose of treatment),
- •Local or locally advanced disease (stage I to III),
- •Treatment with warfarin,
- •Uncontrolled hypercalcemia,
- •Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
- •Known complete dihydropyrimidine dehydrogenase (DPD) deficiency,
- •Treatment with any other investigational medicinal product within 28 days prior to study entry,
- •Symptomatic carcinomatosis with occlusive symptoms or ascites requiring paracentesis,
- •Other serious and uncontrolled non-malignant disease (e.g. active infection requiring systemic therapy, coronary stenting or myocardial infarction, or stroke in the past 6 months),
- •HIV-infected patients or otherwise known to be HIV-positive,
- •Untreated hepatitis B or C,
- •Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for > 5 years,
- •Concomitant administration of prophylactic phenytoin and live attenuated virus vaccine such as yellow fever vaccine 28 days prior to the first dose of treatment.
- •Patient under guardianship, curatorship or under the protection of justice
研究组 & 干预措施
trifluridine/tipiracil
35mg/m² BID (PER OS) (one cycle every 4 weeks)
干预措施: Trifluridine/Tipiracil (Drug)
结局指标
主要结局
Rate of patients free of trifluridine/tipiracil dose reduction or postponement of cycles of > 7 days at 6 months or at progression or death or stop of treatment for another cause than neutropenia if observed in 6 months.
时间窗: At 6 months
To assess, in mCRC patients treated with trifluridine/tipiracil after the introduction of G-CSF in a secondary prevention attempt, the rate of patients free of trifluridine/tipiracil dose reduction or postponement of cycles of \> 7 days at 6 months from G-CSF first intake date or at progression or death or stop of treatment for another cause than neutropenia if observed in the 6 months.
次要结局
- Progression free survival (PFS)(Up to 30 months)
- Disease control rate (DCR)(Up to 30 months)
- Overall survival (OS)(Up to 30 months)
- Clinical or biological factors at baseline associated with the occurrence of grade 3-4 neutropenia(Up to 30 months)
- Objective response rate (ORR)(Up to 30 months)
- Safety descriptive analysis(Up to 30 months)
- The rate of dose reductions(Up to 30 months)