Les Pavillons-sous-bois, France

The Effect of Natural Carbonated Mineral Water Consumption on Gastrointestinal Transit and on Gut Microbiota in Subjects With Functional Constipation: A Randomized, Placebo-Controlled Pilot Trial

A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer)

Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)

A New Posaconazole Dosing Regimen for Paediatric Patients With Cystic Fibrosis and Aspergillus Infection

Cystic fibrosis (CF) is the most common inherited life-limiting disease in North European people affecting 90,000 people worldwide with about 45,000 registered in the Patient Registry of the European Cystic Fibrosis Society (ECFS). Progressive lung damage caused by recurrent infection and persistent inflammation is the major determinant of survival with a median age of death at 29 years. Approximately 60% of CF patients are infected with A. fumigatus, a ubiquitous environmental fungus,and its presence is associated with accelerated lung function decline. Half of the patients infected with Aspergillus are <18 years of age. Evidence to guide clinical management of CF-related Aspergillus disease is lacking. A recent survey showed considerable variability in clinical practice among CF consultants. Two-thirds would treat Aspergillus colonization in patients with CF and two-thirds would use an azole antifungal in addition to steroids in the first line treatment of CF-related allergic bronchopulmonary aspergillosis (ABPA). The results of this survey underscore the limited evidence available to guide management of Aspergillus infection in CF. Posaconazole, being one of the 4 licensed triazole antifungals with good efficacy against Aspergillus species has been chosen as the study drug as it has a better tolerability compared to itraconazole, less toxicity and drug-drug interactions compared to voriconazole and can be administered once daily. Posaconazole is licensed in Europe for the prevention of invasive aspergillus in adult neutropenic patient populations and as salvage therapy for invasive aspergillosis. Several studies have reported on the safety and tolerability of the use of posaconazole in children and adolescents with either haematological malignancies, or chronic granulomatous disease, or those undergoing haematopoietic stem cell transplantation. Currently, no dosing algorithm is available to guide posaconazole dosing in children.

Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)

Relapse of AML is driven by chemotherapy resistant stem cells. One mechanism of chemotherapeutic resistance in AML is the overexpression of the protein B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein which sequesters intracellular activators of apoptosis. Venetoclax is a selective, potent, orally bioavailable, small molecule inhibitor of BCL-2 that restores programmed cell death in cancer cells. This is a trial for children, adolescents and young adults with 2nd relapsed AML or 1st relapsed AML unable to receive additional anthracycline. This is randomized trial of venetoclax in combination with intensive chemotherapy (fludarabine/cytarabine/gemtuzumab ozogamicin) for the first two cycles (42-day-cycles) that would inform and evaluate if this agent is an effective option for this population to improve its poor prognosis. Participants can receive up to two cycles of induction chemotherapy before hematopoietic stem cell transplantation (HSCT). If participants who have perceived clinical benefit cannot be transplanted after the 2 cycles, maintenance treatment may be given at the discretion of the investigator. In Arm B (experimental arm), participants can continue venetoclax if they have perceived clinical benefit, and maintenance therapy will combine venetoclax with azacitidine for a maximum of 24 cycles. In Arm A (control arm), participants will receive azacitidine in monotherapy. Maintenance is continued until clinical progression or unacceptable toxicity with a maximum of 24 cycles.

The FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials

This is an open-label, continuation study for participants receiving study intervention(s) in an encorafenib/binimetinib Parent Study. The study is being conducted under a Master Protocol for Encorafenib/Binimetinib Continuation Sub-Studies with an individual encorafenib/binimetinib continuation sub-study protocol for each eligible Parent Study. Approximately 75 participants from potentially qualifying Parent Studies will be included in this Encorafenib/Binimetinib Continuation study. This continuation study includes multiple sub-study protocols to allow participants from each of the following parent studies: C4211001 - NCT01320085; C4211003 - NCT01849874; C4221003 - NCT03864042; C4221005 - NCT01543698; C4221006 - NCT03911869; C4221009 - NCT02928224; C4221010 - NCT01436656; C4221013 - NCT02159066; ANCHOR-CRC - NCT03693170

Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) in children has become a highly curable disease with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy with an overall remission rates equal to or higher than 98% and cure rates now exceeding 80% 1-9. Based on data coming from adults indicating that at least standard-risk APL patients may be cured without chemotherapy (i.e., with a treatment combining arsenic trioxide (ATO) and ATRA only) 10-12, this ICC APL 02 study was designed with the aim of validating the efficacy of a treatment combining: - ATO and ATRA in newly diagnosed APL standard-risk (SR) children and adolescents and - ATO, ATRA and gemtuzumab ozogamicin (GO) in newly diagnosed APL high-risk (HR) children and adolescents. Following one induction course of treatment combining ATO and ATRA +/- GO depending on risk stratification, patients will receive 4 ATO/ATRA based consolidation blocks. This is the first pediatric trial delivering a non-chemotherapy-based treatment for children with APL, being the whole treatment based on the use of ATRA, ATO (and GO in HR patients). The aim of the study is to demonstrate at least an equivalent efficacy and safety of this treatment not containing cytostatic agents compared to the standard protocols combining ATRA and chemotherapy (i.e. ICC APL Study 01). The trial is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR-positive for the PML-RARα transcript and less than 18 years of age. This will be an international study, comprising the most important pediatric European groups, expecting to recruit 46 and 43 patients in SR and HR arms, respectively, in 3 years. The duration of study recruitment will be 36 months with a minimum follow-up per patient of 2 years. The evaluation of morphological CR will be carried out after induction therapy, prior to the first block of consolidation therapy. MRD results after induction will not have an impact on subsequent therapy. By contrast, MRD results after the third consolidation course will influence the subsequent treatment, MRD-positive patients being eligible to rescue treatment, including hematopoietic stem cell transplantation (HSCT). BM aspirates will be repeated after the end of therapy, and 3 months, 6 months, 9 months and 12 months after treatment discontinuation. This is a collaborative international study in APL in children and adolescents aimed at providing information about procedures for the entry, treatment and follow-up of pediatric patients with APL. It is not intended that this document be used as an aide-memoir or guide for the treatment of other patients. Every care has been taken in its drafting, but corrections and amendments may be necessary. Before entering patients into the study, clinicians must ensure that the study has received clearance from their Local Research Ethics Committee and any other necessary body.

Stroke Thrombectomy and Aneurysm Registry

Neoadjuvant and Adjuvant Ribociclib and ET for Clinically High-risk ER+ and HER2- Breast Cancer

All patients will receive letrozole plus ribociclib as neoadjuvant therapy. Treatment will consist of six 28-days cycles of daily letrozole (2.5mg; continuous) and ribociclib (600 mg/day; 3 weeks ON and 1 week OFF). In pre-menopausal and men patients, monthly LHRH agonists will be added to letrozole and ribociclib, beginning at least two weeks before starting letrozole and ribociclib. After finalization of neoadjuvant treatment, patients will undergo surgery. Surgery samples of the residual tumor tissue (or tumor bed if pathological complete response [pCR] is achieved) will be collected regardless of whether they completed full neoadjuvant treatment. This is not a randomized study; therefore, adjuvant treatment will be decided according to centrally assessed ROR and pathological stage after surgery. Patients are considered responders if they achieve a pCR or have ypN0 and ROR ≤ 30 or ypN1mi (cancer the lymph node is > 0.2 mm but < 2 mm) and ROR ≤ 20 or ypN1 and ROR ≤ 10. All patients with ypN0 and ROR > 30, ypN1mi and ROR > 20, ypN1 and ROR > 10 or ypN2-3 are considered non-responders. Patients who progress during neoadjuvant treatment with ribociclib will be considered non-responders. If indicated, adjuvant radiotherapy will be performed after surgery in the responder group and after adjuvant chemotherapy in the non-responders group. Patients considered as responders will continue on treatment after optimal recovery of surgery and radiotherapy if indicated. Treatment with ribociclib (400 mg/day; 3 weeks ON and 1 week OFF) in the adjuvant setting will be maintained for 30 months approximately corresponding to 33 cycles. Letrozole treatment duration must be of at least 5 years. Visits during ribociclib treatment will be scheduled every three cycles. At the end of ribociclib treatment, visits will be every 6 months until 5 years from last patient's surgery. Patients considered as non-responders will be treated with standard chemotherapy regimens. Patients will continue treatment with ribociclib and letrozole after optimal recovery of adjuvant chemotherapy and radiotherapy if indicated. Treatment with ribociclib (400 mg/day; 3 weeks ON and 1 week OFF) in the adjuvant setting will be maintained for 30 months approximately corresponding to 33 cycles after adjuvant chemotherapy. Endocrine therapy treatment duration must be of at least 5 years. Visits during ribociclib treatment will be scheduled every three cycles. At the end of ribociclib treatment, visits will be every 6 months until 5 years from last patient's surgery. During adjuvant treatment (both responders and non-responders), letrozole can be switched to another aromatase inhibirtor (AI). Tamoxifen is only permitted after the 30-day post ribociclib visit, according to investigator criteria. Maintaining suppression of ovarian function by luteinizing hormone releasing hormone (LHRH) agonists during adjuvant treatment is mandatory (if AI are taken)/ recommended (if tamoxifen is taken) in premenopausal and men patients unless there is unmanageable toxicity. Adjuvant hormonal treatment of patients who progress during neoadjuvant Ribociclib will be at the investigator's discretion. Blood samples for ctDNA will be collected at screening, C2D1, pre-surgery, post-surgery, and every 6 months during the adjuvant period. Blood samples will be also collected in case of recurrence. The global end of the study is defined as the date when the last patient accomplishes 5 years of follow up after surgery. The total duration of the study is expected to be 32 months for enrollment, 3 years of adjuvant treatment (including 2.5 years of ribociclib treatment), and additional 2.5 years of follow-up.

Medtronic Deep Brain Stimulation (DBS) Therapy for Epilepsy Post-Approval Study (EPAS)