Predicting Reactions and Effects of Drugs Immunotherapy and Complications Through Oncosafety (PREDICTO Clinical Study)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Identification of a predictive baseline signature who maximize the rate of prediction of severe iRAE
研究概览
简要总结
Immune Checkpoint Inhibitors (ICI) have revolutionized cancer therapy, providing unprecedented responses in a wide range of malignancies. However, they induced various immune-related adverse events (iRAE) that can be life-threatening. About 20% of patients treated with an ICI monotherapy, and up to 60% of patients treated with a combination of ICIs, experienced a severe iRAE. Most side effects are reversible if managed early, but can affect survival and quality of life, leading to treatment interruptions or hospitalization. Some of these irAEs, particularly those affecting hormonal functions, may be irreversible and persist even after treatment discontinuation.
The development of predictive biomarkers of such toxicities is an unmet medical need. The variety of mechanisms involved in iRAE, and the lack of effective animal models, could probably explain why the topic remains largely unexplored. To date, some biomarkers predictive of the occurrence of iRAE, irrespective of the type of organ affected, have been identified by state-of-the-art techniques on small cohorts prior to treatment initiation, but none is individually robust enough to be used in daily practice.
We hypothesize that a signature derived from the integrative analysis of various biological parameters (immunomonitoring, auto-immunity features, viral monitoring, microbiota monitoring, fragmentome analysis, pharmacokinetics, radiomics and genetics), available in routine hospital practice, could answer this question, and thus enable the development of specific prevention strategies
The objectives are :
Primary objective:
Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected.
Secondary objectives:
- Identify a predictive signature for severe iRAE including baseline and T1 data, irrespective of the type of organ affected.
- Identify a baseline predictive signature for organ-specific severe iRAE.
- Identify a predictive signature for organ-specific severe iRAE including baseline and T1 data.
- Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for patient receiving an anti-PD(L)1 in monotherapy.
- Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for patient receiving an anti-PD(L)1 in combination.
- Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for each specific immunotherapy received.
- Compare the predictive signatures between responders and non-responders according to RECIST 1.1 in order not to overlook the influence of clinical response on the variability observed.
- Describe the results obtained for each biological parameter between severe irAEs and non-severe irAEs patients.
- Describe patient-reported outcomes and quality of life parameters.
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
- •Adult patient (≥18 years old)
- •Patient presenting an histologically or cytologically confirmed solid tumour malignancy
- •Patient scheduled to receive his/her first infusion of immunotherapy with anti-PD1, anti-PDL1, anti-CTLA4, anti-LAG3, alone or in combination, as part of standard care, in all validated solid oncology indications.
- •Patient must have at least one measurable lesion according to RECIST 1.1 criteria
- •Patient treated at AP-HM in one of the CEPCM-affiliated departments.
- •Patient able to comply with study procedures and follow-up schedule
- •Patient who has been informed about the study and signed the consent form
- •Patient who is a beneficiary or entitled beneficiary of a social security scheme
排除标准
- •Patient previously treated with ICIs
- •Patient whose treatment plan includes targeted therapy, chemotherapy or any other systemic treatment in combination with ICI
- •Patient included in a trial with an experimental molecule
- •Patient has an active autoimmune disease or any other pathology requiring systemic corticosteroid therapy at more than 10 mg prednisone equivalent per day or any other immunosuppressive drug
- •Patients with a history of organ transplantation, hematopathy or hematopoietic stem cell transplantation
- •Patient with history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- •Patient in emergency situations, persons deprived of their liberty by judicial or administrative decision, adults subject to legal protection measures, or persons who are unable to give their consent, or pregnant or breastfeeding.
研究组 & 干预措施
Blood, Throat and skin swabs and Stool additional samples
Blood, Throat and skin swabs and Stool additional samples are collected in parallel of treatment administration throughout visits 1 to 4.
干预措施: Bloodsampling (Other)
Blood, Throat and skin swabs and Stool additional samples
Blood, Throat and skin swabs and Stool additional samples are collected in parallel of treatment administration throughout visits 1 to 4.
干预措施: Pharyngeal swab sampling (Other)
Blood, Throat and skin swabs and Stool additional samples
Blood, Throat and skin swabs and Stool additional samples are collected in parallel of treatment administration throughout visits 1 to 4.
干预措施: Cuteanous swab sampling (Other)
Blood, Throat and skin swabs and Stool additional samples
Blood, Throat and skin swabs and Stool additional samples are collected in parallel of treatment administration throughout visits 1 to 4.
干预措施: Stools sample collection (Other)
结局指标
主要结局
Identification of a predictive baseline signature who maximize the rate of prediction of severe iRAE
时间窗: From enrollment to the end of following after 12 months
The primary endpoint is the identification of a predictive baseline signature who maximize the rate of prediction of severe iRAE among patients who had a severe iRAE (iRAE + patients) and minimize the rate of prediction of severe iRAE among patients who had not a severe iRAE (iRAE- patients), we choose a minimum of 70% of prediction in iRAE + population and a maximum of 15% of prediction in iRAE- population.
次要结局
- Identification of signatures for organ-specific severe iRAEs(From enrollment to the end of following after 12 months)
- Identification of signatures for severe iRAEs(From enrollment to the end of following after 12 months)
- Assesment of safety according to NCI-CTCAE v5.0 criteria(From enrollment to the end of following after 12 months)
- Identification of signatures for organ-specific severe iRAEs at baseline and T1(From enrollment to the end of following after 12 months)
- Identification of signatures for severe iRAEs in patients receiving anti-PD(L)1 monotherapy.(From enrollment to the end of following after 12 months)
- Identification of signatures in patients receiving combination immunotherapy(From enrollment to the end of following after 12 months)
- Identification of baseline signatures for each specific immunotherapy class.(From enrollment to the end of following after 12 months)
- Comparison of predictive signatures between responders and non-responders (RECIST 1.1).(From enrollment to the end of following after 12 months)
- Rate of biological parameter variation between severe and non-severe iRAE patients(From enrollment to the end of following after 12 months)
- Assessment of PRO-CTCAE(From enrollment to the end of following after 12 months)
- Evaluation of quality of life via EORTC QLQ-C30 questionnaire(From enrollement to the end of following after 12 months)
- Evaluation of quality of life via EQ-5D-5L questionnaire(From enrollement to end of the following after 12 months)