Cowden Syndrome

Researchers are investigating targeted drug therapies for patients with vascular malformations that are resistant to standard treatments or for whom standard treatments are unsuitable. These vascular malformations are classified as either slow-flow or fast-flow types, driven by genetic changes in two specific signalling pathways. This phase II open-label trial aims to evaluate the effects of 48 weeks of treatment using either alpelisib for slow-flow vascular malformations with PI3K pathway mutations or mirdametinib for fast-flow vascular malformations with MAPK pathway mutations. Participants are divided into two treatment groups based on their vascular malformation type and genetic mutation. Those with slow-flow malformations and PI3K pathway mutations will receive alpelisib, an oral PI3-kinase inhibitor, for 48 weeks followed by a 24-week follow-up. Those with fast-flow malformations and MAPK pathway mutations will receive mirdametinib, an investigational oral MEK inhibitor, also for 48 weeks followed by 24 weeks of follow-up. Both treatments are given as monotherapy and involve genetic testing before enrollment to confirm mutations. Throughout the study, participants will undergo various assessments including symptom evaluations using the Vascular Malformation Patient Specific Outcome Measure VM-PSOM and OVAMA questionnaires, MRI scans to measure lesion size, and monitoring for adverse events. The primary outcome is the improvement in the most significant symptom after 48 weeks of treatment. Follow-up visits continue for 24 weeks after treatment ends to monitor ongoing effects and safety. The total participation duration for each patient is approximately 72 weeks.

RASopathies are genetic conditions that affect childrens development, causing physical, cognitive, and behavioral challenges. This research aims to find out if Acceptance and Commitment Therapy ACT, a technique that helps people accept difficult thoughts and feelings, can help caregivers of children with RASopathies manage parenting stress. The study includes an initial pilot phase followed by a randomized trial to compare immediate versus delayed intervention effects. The study involves an 8-week ACT intervention delivered remotely through a mobile app called MetricWire. Participants watch weekly videos lasting 9 to 17 minutes and engage in coaching sessions via video chatone 75-minute session in week 1 and shorter 20- to 30-minute sessions in weeks 3 and 6. The trial has two phases a pilot study where all participants receive the intervention immediately, and a randomized controlled trial where participants either start the intervention right away or after approximately 2 months on a waitlist. Caregivers aged 18 or older who care for a child under 18 with a RASopathy and live with the child at least half the time are eligible. They will complete brief daily surveys five days a week and longer questionnaires before and after the intervention, as well as three months later. These assessments measure parenting stress, mindfulness, self-compassion, and related factors. The study monitors feasibility, acceptability, and changes in stress levels over time using electronic assessments and questionnaires.

Researchers are evaluating new approaches to cancer genetic counseling to improve patient engagement with genetics teams. This study includes two trials the EfFORT Trial focuses on cascade genetic testing, where healthcare providers reach out directly to family members at risk to recommend testing, comparing it to the usual method where patients inform their relatives. The STRIVE Trial studies an online portal intervention to help patients with uncertain genetic test results and their primary care providers stay updated on new information about those results. The EfFORT Trial compares a control group where patients share a family letter with relatives against an intervention group where providers contact relatives directly, offering telegenetics counseling and at-home saliva testing. The STRIVE Trial compares standard care with a digital portal called MyGene Portal, which offers ongoing access to educational materials, communication tools, medical history updates, notifications about result reclassification, and reminders for follow-up visits. Both trials include standard post-test genetic counseling and follow-up recommendations. Participants will be involved through genetic counseling sessions, use of the online portal, and study surveys. Assessments include measuring how often genetic testing occurs in relatives and participant-perceived quality of care over 12 months. Researchers monitor engagement with the interventions, update family medical histories, and provide support for uncertain genetic results. The study is randomized and open-label, with participants actively involved in education, counseling, and communication activities throughout the study period.

Researchers are investigating the usefulness of family-based whole-genome sequencing WGS to identify cancer predisposition syndromes CPS in children and adolescents newly diagnosed with cancer. These syndromes are caused by inherited mutations in cancer predisposition genes and are linked to a higher risk of developing certain cancers. The study aims to understand how often CPS occurs in this population and the impact of germline sequencing on patients and their families. This is a multicenter prospective observational study focusing on clinical benefits and utility of WGS compared to traditional clinical information. Participants will undergo family-based germline whole-genome sequencing to identify genetic variants related to cancer predisposition. The results will be discussed in multidisciplinary meetings, and referrals to Cancer Genetics Clinics for further evaluation and genetic counseling may be recommended. Additionally, the study includes a psychosocial component to assess how the sequencing process affects patients and their families. The study follows patients for up to five years to analyze psychological impact and cost-effectiveness. During the study, researchers will collect detailed family cancer histories and monitor genetic findings, including inherited and new mutations. The primary outcome measures focus on comparing the detection of CPS by WGS versus clinical factors over two years. Secondary outcomes include mutation types, test turnaround times, surveillance adherence, and psychological effects assessed over five years. Participants will be closely followed to evaluate diagnostic accuracy, genetic counseling outcomes, and the broader impact of sequencing on care and family well-being.

Researchers are studying an experimental blood test that detects early tumors in patients with hereditary cancer syndromes. This test, called cell-free DNA cfDNA analysis, aims to improve cancer screening by identifying cancer sooner than standard methods. The study compares cancer detection rates and timing between patients receiving cfDNA testing and those receiving regular care, while also exploring the impact on patients quality of life and psychological well-being. Participants are divided into two groups the experimental group provides blood samples every four months for four years for cfDNA testing, with results given back to them. Those with positive results will be offered follow-up tests to confirm cancer presence. The control group continues with their usual cancer surveillance without cfDNA testing. Both groups complete questionnaires and interviews to share their experiences and views on the blood test. During the study, participants attend regular blood sample collections, often coordinated with routine clinical blood draws to reduce extra procedures. Researchers measure cancer detection rates over four years and assess if cfDNA testing leads to earlier cancer diagnosis. They also evaluate participants cancer-related worry, anxiety, and quality of life. The study lasts for four years, with ongoing monitoring and support to understand the tests clinical and personal impact.

Researchers are evaluating a mobile health platform called a chatbot that uses artificial intelligence and natural language processing to communicate with patients at an all-Medicaid gynecology clinic. The study aims to compare this chatbot system to usual care to see if it improves recommendations for genetic testing among patients at high risk for familial cancer syndromes. The study also seeks to understand factors that affect patient access to and use of genetic testing services, focusing on inequities. Participants will be assigned to one of two groups. In the chatbot group, patients receive a text message to start a chatbot conversation that collects personal and family cancer history and identifies high-risk patients based on National Comprehensive Cancer Network criteria. The chatbot provides pre-test genetic counseling and notifies clinicians about high-risk patients, who then complete counseling and recommend genetic testing if appropriate. In the usual care group, clinicians collect personal and family cancer history during visits and evaluate risk according to guidelines before counseling and recommending testing. Genetic testing is ordered for interested patients meeting criteria. Participants will be monitored over two years to measure outcomes such as the proportion of patients recommended for genetic testing and the proportion completing testing. The study also assesses patient satisfaction, distress levels, decision satisfaction, facilitators and barriers to genetic testing, and other scales related to inequity in utilization of genetic services. These evaluations include questionnaires and surveys to understand patient experiences and access to care during the study period.

RASopathies are a group of genetic disorders caused by changes in genes that affect the RasMAPK pathway. People with RASopathies may experience developmental problems, cognitive disabilities, poor growth, birth defects, and an increased risk of certain cancers. Researchers aim to learn more about how genes and environmental factors contribute to cancer development and other health issues in individuals with these disorders. Participants include people of all ages who have or may have a RASopathy, as well as their family members. The study is observational and involves collecting detailed personal and family medical histories through questionnaires and reviewing medical records. Participants may provide blood, urine, saliva, or cheek cell samples for genetic testing, and some may have additional tests such as skin biopsies, physical exams, imaging scans, and specialist evaluations. Participation will last indefinitely, with occasional contact by phone or mail and possible follow-up visits. Researchers will monitor various health aspects, including cancer development and other RASopathy-related conditions, using standardized evaluations, biospecimen repositories, and assessments of new clinical features. The study aims to improve understanding of RASopathies and inform cancer screening recommendations for those affected.

Researchers are studying the genetic causes and molecular characteristics of urologic cancers including kidney, prostate, bladder, testis, and penile cancers. These cancers make up a significant portion of cancer diagnoses and deaths in the United States. The goal is to better understand gene pathways involved in these malignancies to aid in developing targeted treatments. This observational study collects blood, urine, and tissue samples from individuals with confirmed or suspected malignant disease or inherited urologic cancer risks. Participants include patients with biopsy-proven or suspected malignancies and their blood relatives who may have inherited cancer risks. Samples of blood, urine, and both normal and malignant tissue are collected during clinical visits and surgeries. These specimens are stored in a tissue bank and used for genetic sequencing, protein expression analysis, and research on cancer gene mutations and biochemical pathways. The study also investigates quality of life in men with prostate cancer and responses to existing and novel cancer therapies. During the study, participants undergo eligibility screening and may provide biological samples at initial and periodic visits. Tissue samples are collected during clinically indicated surgeries. Researchers analyze these samples using molecular and biochemical methods to identify genetic differences and markers. Participants may be contacted if significant health-related findings arise. The study involves ongoing assessments of genetic and molecular data and quality of life, continuing over time without a fixed end date.

Researchers are studying colorectal cancer CRC, endometrial cancer EC, and hereditary cancer syndromes to better understand genetic predispositions and new treatment possibilities. The study focuses on discovering new mechanisms in intestinal cancer development, identifying genes and proteins for targeted therapies, and exploring how the immune system can recognize and eliminate tumor cells. It aims to create a valuable resource for future research on hereditary and sporadic cancer cases. Participants provide tissue, blood, and clinical data collected during routine clinical care procedures such as gastrointestinal endoscopies, surgeries, transvaginal ultrasounds, hysteroscopies, and endometrial biopsies. Samples include normal mucosa, polyps, tumors, and blood used for molecular and genetic studies. Organoids derived from these tissues will be used to assess drug sensitivity and study cancer biology. During the study, participants clinical data, family history, and biospecimens are collected and stored for future research. Data includes demographics, medical history, treatment details, and outcomes from standard care. This observational study does not involve experimental treatments but contributes to a hereditary cancer registry and tissue repository. The study plans to continue follow-up until 2027, assessing novel genetic mechanisms and immune responses over seven years.

Researchers are studying an investigational blood test called the GRAIL Galleri test, designed to detect many types of cancer early. This study focuses on people at slightly higher than average risk of developing certain cancers, including those with genetic cancer predisposition syndromes or a strong family history of cancer. The goal is to evaluate the benefits and possible harms of this multi-cancer early detection MCED test in a prospective, interventional setting lasting up to three years. Participants will undergo baseline questionnaires and a blood test using the Galleri MCED test. Depending on the test result, follow-up may vary those with a negative test will have recommended cancer screenings and a follow-up phone call one year later, while those with a positive test may have additional clinic visits, lab tests, biopsies, surgeries, or imaging scans such as ultrasound, CT, or MRI. If cancer is confirmed, participants will complete a post-diagnostic questionnaire. During the study, participants will complete questionnaires and blood tests at scheduled visits. Researchers will monitor cancer detection rates up to two years and track outcomes like cancer stage at diagnosis, positive predictive value at 12 and 24 months, time to diagnostic resolution, participant anxiety, quality of life, and costs related to follow-up testing. The study expects to enroll about 1,000 people and lasts up to three years, including follow-up assessments and safety monitoring.