Clinical Trials

Background: People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing. Objective: To learn if nilotinib and paclitaxel will benefit people with rare cancers. Eligibility: People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors. Participants will repeat the screening tests during the study. Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle. Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have. Participants may have optional tumor biopsies. Participants can stay on the study until their disease gets worse or they have intolerable side effects. Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

This phase I trial studies the side effects and best dose of CB-5339 in treating patients with solid tumors that has spread to other places in the body (advanced) or lymphomas. CB-5339 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

This Phase 2a study will assess the safety, antiviral activity, and pharmacokinetics (PK) of ABI-H2158 administered once daily for up to 72 weeks in combination with entecavir (ETV) in participants with chronic hepatitis B virus (HBV) infection.

The 22q11.2 microdeletion syndrome (22q11.2DS) is a rare disease with a psychiatric phenotype. Indeed, the diagnosis of schizophrenia is made in 5 to 10% of adolescents and 25 to 40% of adults carrying the 22q11DS. Thus, although this pathology has been able to provide a genetically homogeneous model for the study psychosis etiology, it is not currently possible to establish a link between genomic rearrangement and psychotic symptoms. However, this robust model of genetic vulnerability could provide us a lot of translational informations about schizophrenia genetics. To go furthermore, twin studies have provided us precious data for the study of hereditary diseases. Combining this two approaches, the translational 22q11.2 project proposes a molecular study of two monozygotic 22q11.2DS twins discordant for the psychiatric phenotype -one carrying schizophrenia and the other having no psychiatric symptoms-.

The purpose of the pre-study screening is to test for DNA abnormalities or biomarkers.

The overarching intention of the Eating Disorder Genetics Initiative (EDGI) is to lay the foundation for all future genomic discovery in eating disorders--anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED)--by exploring both genetic and behavioral factors. To do this, information will be collected from 4000 people who have provided DNA samples for the Anorexia Nervosa Genetics Initiative (ANGI) and the same information and DNA will be collected from an additional 16,000 people. The goal is to better understand eating disorders and how they relate to each other so that better treatments can be developed.

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. KeytrudaTM (pembrolizumab) has been approved by the FDA and the EMA for the therapy of with chemotherapy pretreated NSCLC patients with PD-L1 expression (TPS ≥ 1%) on tumor cells. In addition, pembrolizumab was approved for the first line treatment of metastatic NSCLC patients with high PD-L1 expression (TPS ≥ 50%) on tumor cells. Pembrolizumab will be given in a flat dose of 200 mg i.v. every 3 weeks until disease progression, toxicity or patient withdrawal for a maximum of 2 years. Patients with untreated advanced stage lung adenocarcinoma, without an EGFR mutation or ALK translocation, will be included.

Microbiota contributes to the immunological, hormonal and metabolic homeostasis of the host. As in all natural orifices in the body, there is also a microbiota and mycobiota specific to the vagina. On the other hand, the sonographic short cervix in the second trimester of pregnancy is associated with preterm delivery, which may be an important cause of mortality and morbidity in the neonatal period. American Society of Obstetricians and Gynecologists (ACOG), British Royal Society of Obstetricians and Gynecologists (RCOG) and the American Society of Maternal Fetal Medicine (SMFM) suggest that the measurement of transvaginal sonographic cervical length at 20-24 gestational weeks for the screening of preterm birth. The aforementioned associations also recommend the use of progesterone in the treatment of women who diagnosed with short cervix by transvaginal ultrasonography due to the fact that progesterone is an effective medication in the prevention of preterm birth (Grade B). Previous vaginal microbiota studies have shown that some bacterial species such as Lactobacillus insers cause a predisposition to premature labor in women with a short cervix. However, the prominent lack in these studies is that the eukaryotic fungi in abundant vaginal flora have not been evaluated. On the other hand, it was already shown that progesterone treatment is able to prevent only 45% preterm birth in women with short cervical length. This observational prospective study thus aims to evaluate the variety of microbiota and/or mycobiota in pregnancies resulting in preterm birth and those who give birth at term. Although women with short cervical length receive progesterone regularly from the second trimester, the preterm birth may occur. In this study, the investigators also aim to evaluate the patterns of microbiota and mycobiota from vaginal swabs of women who had preterm birth with short cervical length and postpartum swabs of the placenta and fetal oral cavity.

The necessity for early detection and hence improving the outcome of treatment of pneumonia is critical especially SARS-CoV-2 induced cases. This work was designed to evaluate the potential application of measuring circulating epigenetic markers namely, miR-744, miR-24, miR-124, miR-155, miR-19a, miR-122, miR-21, miR-223, let-7f, miR-146, miR-196, miR-136, P13-K, miR-9 expression, and DNA methylation profiling of the ACE2, TMPRSS2, PARP, HOX1 genes in Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 with/without pneumonia and severe acute respiratory syndrome (SARS) patients as an attempt to evaluate the potential benefits of these new circulating, prognostic, epigenetic markers for Turkish patients.

Study rationale 1. An increasing proportion of the worldwide population is being infected with COVID-19. 2. There are ongoing and currently unanswered safety concerns about the effects of COVID-19 on reproductive health. 3. It will be immensely reassuring to rapidly report that COVID-19 has no detectable effects on male endocrine or sperm function. Conversely, if COVID-19 does impair male reproductive health, appropriate screening can be performed in couples trying to conceive, and further research can be undertaken. 4. The proposed study will be simple, rapid, and authoritative for the UK and worldwide.

The primary objective of this study is to establish differences in susceptibility to SARS CoV-2 infection among health care workers (HCW) highly exposed to patients with COVID-19 diagnosis. To ascertain this issue, we evaluated: - Changes in receptor polymorphism (ACE2 and CD26 receptor study. - SARS-CoV-2 CD4/CD8 T cell response (CTL) - Different KIR phenotypes

The purpose of this study is to evaluate the prevalence of 4 or more DNA-repair gene defects in a population of men with metastatic Prostate Cancer (PC) and to use the reported DNA-repair gene defects to assess biomarker eligibility for niraparib interventional studies.

CDK13 related disorder is mainly characterised by developmental delay (DD) and intellectual disability (ID), ranging from mild to severe, and malformation syndrome. The aims of this study are first to better delineate the clinical phenotype, as well as the neuropsychological profile, and the brain MRI characteristics; and, second, to study the epigenetic signatures in a cohort of individuals with CDK13 intragenic pathogenic variants. This work will conduct to a MD thesis of a clinical resident geneticist in France. Physician that will participate will fill an Excel sheet regarding the clinical and neuropsychological assessment. The investigators will be also happy to have either CD-ROM or a link to have access to the brain MRI data as well as a DNA sample with a minimum 0.5ug of peripheral blood genomic DNA. The investigators will gather the DNA in Montpellier genetic lab (Dr Mouna BARAT) and send the batch to the Dr Sadikovic' lab. Between 2019 and 2020, The investigators have already recruited data from individuals with CDK13 pathogenic variants from France and several European genetic centres.

This study aims to study the kinetics of ctDNA levels after the first dose of immune checkpoint inhibitor in patients with recurrent or metastatic head and neck cancer. This is an important study to understand the optimal timing for ctDNA quantitation for future studies in immunotherapy, though further validation would be needed in other tumor types. It may help standardize the most relevant blood collection time points so that patients will not be subjected to multiple blood draws at random time points in future liquid biopsy trials.

This research study will include patients with high risk locally advanced head and neck squamous cell carcinoma (LA-HNSCC) of the oral cavity, oropharynx, hypopharynx or larynx and patients that are starting on standard definitive treatment. Patients with both stage III HPV positive and stage III HPV negative will be included. In this study, we aim to evaluate feasibility of ctDNA and/or HPV DNA detection in real time in high-risk LA-HNSCC.

This is a randomized, double blind, Phase 1 study. There will be a 12-week comparison of the safety of DS-01 versus placebo with a secondary outcome measure of the efficacy in a cohort of 100 men or women with IBS with constipation. 50 IBS-C or IBS-M patients will receive DS-01 (Daily Synbiotic, once daily) for 12 weeks, while 50 IBS-C or IBS-M patients will receive the placebo (once daily). Safety is a paramount concern in the study design and will be monitored carefully throughout the study. Study subjects will also receive extensive education on use of the synbiotic.

In the United States, healthcare providers prescribe over 270 million antibiotic prescriptions each year. While antibiotics have transformed medicine and methods of treating life-threatening bacterial infection, broad spectrum antibiotics also induce disruption of resident gut microbial communities by altering both composition and function. This disruption of microbial community dynamics has been demonstrated at the taxonomic level, yet the extent of functional disruptions to microbial metabolic output and host cells remains understudied in humans. This study explores the impact of a broad spectrum antibiotic cocktail on microbial communities throughout the gastrointestinal tract, and the impact of a defined, multi-strain consortia of probiotic organisms following antibiotic exposure.

This a prospective real-world navigation study using tumor DNA sequencing technology to sequence genes of previously treated and refractory gastrointestinal tumors, which are generally considered to be highly heterogeneous and complex, to screen potential molecular targeted drugs for individualized treatment. This study may provide feasibility and response information, which will be the basis for designing better randomized trials, which may change the pattern of cancer treatment. If the hypothesis is finally proved, it will help doctors and molecular biologists to choose the best drug (or combination of drugs) based on the individual oncogenomics of each patient.

Although epigenetics has been identified as one of the most relevant pathophysiological components in the development of cardiovascular diseases, there is still considerable difficulty in finding markers of epigenetic damage useful in clinical practice. Moreover, these markers could be useful to predict the onset and severity of disease as well as to stratify stratification the prognostic risk during the follow-up. The aim of this project will be to evaluate the genome wide DNA methylation status in circulating CD4+ T cells and CD8+ T cells in patients with acute coronary syndromes (ACS), atrial fibrillation (AF) and with ACS in the presence of AF.

1. Inclusion of 5 families Inclusions will be made by the clinical genetics department of the Rouen University Hospital (monocentric study) and will correspond to trios of parents + child with unexplained developmental abnormalities. The inclusion of patients will be integrated in routine care and will have as immediate benefit for the included families the extensive analysis of the proband and their parents' genomes by short and long read sequencing techniques, which represent the most comprehensive diagnostic tests for developmental diseases, and which are not currently routinely available. Inclusion in clinical genetics by clinicians accustomed to prescribing genome-wide analyses will allow clear and complete information to families. Collection of consents. The trio's DNA will already be available at the molecular genetics laboratory, and a new blood sample may be proposed if necessary. Collection of sperm from the father. 2. Identification of a large set of de novo mutations. Extraction of blood DNA and sending for sequencing of the complete genome to the National Centre for Research in Human Genomics (CNRGH, Evry), in the framework of a collaboration already initiated. Analysis of the sequencing data thanks to the already existing expertise in Rouen. Identification of about 40-120 de novo mutations per trio. At this stage: interpretation of the variations identified with the secondary objective of identifying the cause of the disease in children. Long read genomes will allow to phase the de novo variants to the paternal or to the maternal haplotype. 3. Search for de novo mutations in paternal sperm samples. Extraction of spermatic DNA. Design of a sequencing panel targeting the genetic variations identified in the different trios. Preparation of the libraries, targeted high throughput sequencing at great depth thanks to the techniques and equipment already operational. Specific search for the de novo variations identified in the probands (in 2.), with for each evaluation of (i) the presence of the variation in the sperm sample, (ii) the quantity of mosaicism, reflecting the proportion of carrier spermatozoa and therefore the risk of recurrence, (iii) the presence of my variation in the blood sample of both parents in deep sequencing.