Immunological Variables Associated to ICI Toxicity in Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 441
- 试验地点
- 2
- 主要终点
- Modification(s) in the immune blood markers of treated subjects on treatment.
研究概览
简要总结
This is a monocentric, prospective, pilot study that will enrol 435 subjects with solid tumours that are treated with immune checkpoint inhibitor(s) (ICI) alone or in combination with chemotherapy or targeted therapy.
For enrolled subjects, clinical and laboratory evaluations will be performed and reported at different time points:
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Early (4-6 weeks after treatment start)
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Midtime (8-11 weeks after treatment start)
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Late (13-18 weeks after treatment start)
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At the occurrence of immune-related adverse events (irAEs), clinical and laboratory evaluation will be performed at two principal time points:
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For the 1st time of any grade 1 or 2 irAE if the subject developed it.
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For the 1st time of any grade 3 or 4 irAE if the subject developed it.
详细描述
Advances in treating patients with immunotherapy has dramatically changed cancer morbidity and mortality. Immune checkpoint inhibitors (ICI), alone or combined with other drugs, are currently used both as standard of care or in experimental settings for various cancers. Currently, ICI treatment induces objective clinical responses in 20-40% of patients, which varies by tumour type. A significant risk of immune-related adverse events (irAE) is also associated with ICI treatment, including the onset of autoimmune diseases. While the incidence of irAE is highly variable and influenced by many factors, phase I and II trials reported rates from 10% to 80% for any grade irAE while an irAE of grade 3 or higher was observed in 2.5% to 18% of subjects. Despite the fact that older adults represent the growing majority of patients diagnosed with cancer, the efficacy and toxicity of ICI in older patients, alone or in combination with other agents, remains controversial. Presently, the specific immune mechanism(s) driving irAE are unknown and biomarkers that predict their onset, particularly high-grade irAE, are urgently needed. The identification of predictive clinical, laboratory and immunological biomarkers (blood and tissue) for toxicity will more accurately identify and quantify patients who are at risk for ICI therapy. Then, this will possibly allow better irAE management.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •ECOG performance status ≤ 1
- •Must have histologically or cytologically confirmed solid tumour, eligible for treatment with ICI as standard-of-care alone or in combination with another ICI (cohort 1), ICI with chemotherapy (cohort 2), or ICI with targeted therapy (cohort 3) with no restrictions on number of prior systemic therapies
- •All prior anti-cancer treatment-related toxicities (except alopecia) must be ≤ Grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at the time of enrolment
- •Serum pregnancy test (for subjects of childbearing potential) negative within 15 days prior to study medications administration.
- •Women of childbearing potential must agree to use one highly effective method of contraception prior study entry, during the course of the study and at least 7 months after the last administration of study treatments.
- •Men with childbearing potential partner must agree to use condom during the course of this study and for at least 6 months after the last administration of the study treatments.
- •Completion of all necessary screening procedures within 14 days prior to enrolment.
- •Signed Informed Consent form (ICF) obtained prior to any study related procedure.
排除标准
- •Subjects meeting one of the following criteria are not eligible for this study:
- •Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
- •Participation in another clinical trial.
- •Pregnant and/or lactating women.
- •Subjects already receiving ICI.
结局指标
主要结局
Modification(s) in the immune blood markers of treated subjects on treatment.
时间窗: Assessment: between week 13-18 after the first dose of the treatment
Modification(s) in the immune blood markers including cytokines, immune cells and serum autoantibody level of treated subjects.
Modification(s) in the immune blood markers of treated subjects on treatment at the occurence of any grade 1 or 2 irAE.
时间窗: Assessment: Day1 after diagnostic of any grade 1 or 2 irAE
Safety will be assessed and graded by the investigator(s) by using the adverse events reported during the study in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Modification(s) in the immune blood markers of treated subjects on treatment at the occurence of any grade 3 or 4 irAE.
时间窗: Assessment: Day one after diagnostic of any grade 3 or 4 irAE
Safety will be assessed and graded by the investigator(s) by using the adverse events reported during the study in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
次要结局
未报告次要终点
研究者
Mireille Langouo Fontsa
Principal investigator
Jules Bordet Institute