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Despite substantial progress made in the first- and second line mCRC settings, there are still unmet clinical needs for patients harboring BRAFV600E mutations, especially those with microsatellite stability (MSS) / proficient mismatch repair (pMMR) tumor. The overall survival and access to different treatment in the real-life setting are unknown. Moreover, patient prognosis remains poor and therapeutic resistance to combinations with BRAF inhibitors, is at present, nearly universal. Therefore, it seems essential to prospectively collect clinical and biological data about this rare mCRC subtype. These data will allow us to improve knowledge and to identify clinical and biological factors that could drive therapeutic decisions, predict resistance to treatments, and that are prognostic for survival. In this context, we designed this large, prospective, cohort study to collect clinical data and biological samples to be used for research but also to gather real-world clinical data concerning the treatments and the survival outcomes in patients with BRAFV600E mCRC. This collection of clinical and biological data (tumor tissue and blood samples) will allow us to identify predictive and prognostic biomarkers with several research work packages planned: i. To evaluate the circulating tumor DNA (ctDNA) during the metastatic first-, second-, and third-line treatment to: * Evaluate its positive and negative predictive value. * Identify molecular alterations preceding and explaining clinical resistance during BRAF/EGFR inhibition therapy and immunotherapy. ii. To evaluate BRAFV600E mCRC immune environment both at the tumor and blood level (immunomonitoring). iii. To study specific the dMMR/MSI BRAFV600E subgroup. Furthermore, the data collected will describe the therapeutic management of BRAFV600E mCRC patients in the routine-practice setting which will bring very useful data. The results of the COBRAF study could lay the groundwork to better understand BRAFV600E mCRC and to identify prognostic and predictive biomarkers helping the development of new therapeutic approaches in this population.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects the joints and skin in people who have psoriasis (PsO). The main aim of the study is to know how well zasocitinib (TAK-279) works in participants with active PsA based on their previous experience with specific treatments. The participants will be treated with either zasocitinib, or placebo. Participants will be in the study for up to 60 weeks.

Psoriatic arthritis (PsA) is a type of arthritis (swelling and stiffness in the joints) that is frequently seen in trial participants who also have the skin condition psoriasis. It is caused by an overactive immune system where the body attacks healthy tissue by mistake. This study aims to describe the long term usage and effectiveness with risankizumab (RZB) relative to other advanced therapeutic options for the management of PsA in daily clinical practice. Risankizumab is an approved drug for the treatment of psoriatic arthritis. The study will not be conducted in the United States, however it will be conducted in approximately 15 countries and include at least 900 and up to 1200 participants with a 2 to1 ratio of participant allocation between participants receiving risankizumab and participants receiving other advanced therapeutic agents. The therapy is prescribed in the usual manner in accordance with the terms of the local marketing authorization and professional and reimbursement guidelines with regards to dose, population, and indication. All study visits will occur during routine clinical practice and participants will be followed for 24 months. There is expected to be no additional burden for participants in this study.

Intensive combination therapies have revolutionised the management of solid neoplasms, hematologic malignancies, and acquired-immune-deficiency syndrome. These intensive strategies are based on the need to obtain rapid control of disease activity to afford the chance of stable full remission and avoid irreversible complications. The same goal applies to management of RA. Because current therapeutic strategies may fall short of these target goals and fail to improve quality of life in some patients, novel approaches are needed to improve outcomes. RA is a complex disease involving numerous cell types and inflammatory mediators of innate and adaptive immune systems. The investigators are aware that most of combination bDMARD strategies have been associated with little or no incremental benefit in efficacy compared to single-biologic therapy. However, our study will target mechanisms that differ from those in previous studies. Strategies that simultaneously target different pathways involved in the pathogenesis of RA may enhance treatment responses in patients with RA. Of note, baricitinib does not directly block signalling downstream of TNF, even if an indirect effect on TNF production is likely to occur. Targeting multiple inflammatory cytokines in combination may lead to more effective treatment and enhanced clinical responses in patients with RA compared to the current second-line strategies. The different mechanisms of action of baricitinib and anti-TNF, should ensure the efficacy of the combination. No concurrent trial evaluating similar strategies is registered at ClinicalTrial.gov.

Rheumatoid arthritis (RA) is the most common inflammatory joint disorder. Since twenty year and the use of synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological (b)DMARD, remission can be reached. When remission is obtained, the physician has no recommendations for managing a step-down, and future guidelines will be useful to assist the clinician. Recent data suggest that tapering is feasible, but with high risk of flares. Flares are less frequent when bDMARD blood concentration is high. But, the optimal adalimumab concentration to keep before a step of tapering no targeting personal is unknown.

M1095-PSA-302 is a Phase 3, parallel-group, randomized, double-blind, 4-arm, placebo-controlled, multicenter study with risankizumab as active reference arm to investigate the efficacy and safety of sonelokimab 60 mg and 120 mg versus placebo in adults with active psoriatic arthritis who have had a previous inadequate response or intolerance to anti-tumor necrosis factor (TNF)α therapy.

Squamous cell carcinoma of the anus is still a rare disease but its incidence increases mostly due to its association with human papillomavirus (HPV). When localized, the standard treatment combines radiotherapy and chemotherapy with 5FU and mitomycin-C. Chemoradiotherapy (CRT) achieves a good outcome for early stage tumors (T1-T2 tumors without nodal involvement), but more advanced tumors (T3-T4 or N1) are associated with a dismal prognosis. About 35 % of such patients relapse within two years after the end of treatment Recently, for metastatic or recurrent tumors after chemoradiotherapy, a chemotherapy combining docetaxel, cisplatin and 5FU (modified DCF protocol) has given very good results with a median overall survival of 39.2 months in 2 French trials (Epitopes HPV01 and 02). Our idea is to propose a new strategy , associating this chemotherapy (mDCF) followed by chemoradiotherapy to improve efficacy of the treatment for patients with locally advanced anal cancers. To this end, The principal investigator propose a national, multicenter, randomized phase 3 clinical trial to compare induction chemotherapy with mDCF followed by chemoradiotherapy versus standard chemoradiotherapy for locally advanced anal canal cancer. the efficacy of the treatment will be evaluated by comparing disease-related event-free survival at 2 years according to the type of treatment. Other endpoints will also be evaluated such as overall survival and colostomy-free survival, treatment tolerability, response rate and quality of life. This trial will be offered to patients over 18 years of age with locally advanced anal cancer without metastasis (T3-4 or N1). It is open to patients over 75 years of age subject to a favorable evaluation by an oncogeriatrician. It is also open to immunocompromised patients (HIV+) if their immunity is well controlled under antiretroviral treatment.The standard chemoradiotherapy treatment consists of 33 sessions of radiation, one session per day from Monday to Friday for 6.5 weeks. It is combined with chemotherapy that includes mitomycin during the first and fifth weeks of radiation therapy, as well as capecitabine that are taken on the days of radiation therapy.In the experimental arm, this chemoradiotherapy treatment is preceded by 4 sessions of mDCF chemotherapy performed every 2 weeks.After treatment, patients are followed up at 8 weeks, then every 4 months for 2 years, and every 6 months for the last year with clinical examination and imaging (CT and MRI).

OPTICAB is a single-site study in France that aims to compare two hemodynamic management techniques during off-pump coronary artery bypass graft (CABG) surgery: postural mobilization (+/- noradrenaline) versus noradrenaline only. Primary objective is to evaluate how often noradrenaline is needed when managing hemodynamics using postural mobilization (passive leg raising) during off-pump CABG surgery. The study will also compare revascularization rate and post-operative complications among both groups, and assess perioperative hemodynamic management during the 30-day follow up period.

The Alzheimer's disease or related disorders (ADRD) are among the most disabling diseases because of their main features such as cognitive impairment, loss of functional autonomy and behavioural disorders. In absence of current curative treatment, the identification of the predictive risk factors of progression of the disease, evaluated through its main symptoms, represents a major stake of public health. The investigators aimed at developing a database, which includes the patient medical records on a prospective basis, in collaboration with the medical and administrative personal and with the University hospital computer science department. The main objective is to study the predictive factors associated with the change of functional autonomy level, measured every 6 months to 12 months by phone, in a Memory Clinic. The study population would consist in about 1000 patients with ADRD. The length of follow-up of each patient will be 3 years.

The Alzheimer's disease or related disorders (ADRD) are among the most disabling diseases because of their main features such as cognitive impairment, loss of functional autonomy and behavioural disorders. In absence of current curative treatment, the identification of the predictive risk factors of progression of the disease, evaluated through its main symptoms, represents a major stake of public health. The Investigators aim at developing a regional database, which includes the patient medical records on a prospective basis, in collaboration with the medical and administrative staff and with the University hospital computer science departments. The main objective is to study the predictive factors associated with change in functional autonomy level, measured every 6 to 12 months in centres across Region Auvergne Rhone-Alpes in France. The real-life study population will consist in about 5400 patients with ADRD. The inclusion period will be of 3 years, the length of follow-up of each patient will be of 10 years max for a total study length of 13 years.