Clinical Research Directory

Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas (brain tumors that are generally expected to be fast growing and aggressive), diffuse intrinsic pontine gliomas (brain stem tumors), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma that have come back (recurrent), progressed, or have not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may induce changes in the body's immune system, and may interfere with the ability of tumor cells to grow and spread.

Identifying and Caring for Individuals With Inherited Cancer Syndrome

This trial examines approaches to identify and care for individuals with inherited cancer syndrome. The purpose of this study is to offer no cost genetic testing to the general public. Researchers hope to learn the value of providing broad, public-wide testing for high risk cancer types (like hereditary breast and ovarian cancer or Lynch syndromes) instead of only testing people whose families are known to be high risk.

Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes

The goal of this clinical trial is to address care gaps for participants at high risk of breast and ovarian cancer (HBOC), or Lynch syndrome (LS) because of testing positive for specific genetic variants. A patient-centered clinical decision support (PC-CDS) tool will help identify participants with genetic variations and display recommendations for referrals and testing to the clinician and participant at a primary care visit. The main question the study aims to answer is: \- Does clinical decision support for participants with hereditary cancer syndromes improve the use of evidence-based cancer prevention care. Participants being seen in the PC-CDS group are compared to participants being seen in usual care (UC) to see if they are up to date on guideline-based cancer prevention care and to see if participants in the PC-CDS group report more shared decision making and higher rates of self-management of their genetic cancer risks. Participants will be asked to answer survey questions.

Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair

This phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR). Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy with atezolizumab may work better than combination chemotherapy alone in treating patients with dMMR colon cancer.

Integrated Cancer Repository for Cancer Research

The iCaRe2 is a multi-institutional resource created and maintained by the Fred \& Pamela Buffett Cancer Center to collect and manage standardized, multi-dimensional, longitudinal data and biospecimens on consented adult cancer patients, high-risk individuals, and normal controls. The distinct characteristic of the iCaRe2 is its geographical coverage, with a significant percentage of small and rural hospitals and cancer centers. The iCaRe2 advances comprehensive studies of risk factors of cancer development and progression and enables the design of novel strategies for prevention, screening, early detection and personalized treatment of cancer. Centers with expertise in cancer epidemiology, genetics, biology, early detection, and patient care can collaborate by using the iCaRe2 as a platform for cohort and population studies.

Overcoming Barriers to Uptake of Cascade Screening

Lynch syndrome is a genetic condition that increases cancer risk. The public health impact of genetic testing for disease prevention hinges on cascade screening, which is the systematic identification and testing of blood relatives after a family member has been diagnosed with a genetic condition. Despite its importance in disease prevention, only half of first-degree relatives of individuals with Lynch syndrome undergo cascade screening. To address this gap, the study will pilot test an online version of Let's Talk, a novel intervention designed to support and promote cascade screening. This intervention tool is designed to support and encourage more family members to get screened. The purpose of this study aim is to assess the feasibility of the online Let's Talk tool in clinical use by examining implementation and effectiveness outcomes related to the use of the planning tool across three clinics at a large academic-affiliated medical center with patients (n=15) seen by one of five genetic counselors (n=5).

Determining the Prevalence of Muir-Torre Syndrome in Patients With Lynch Syndrome

The main aim of this study is to determine the prevalence of Muir-Torre syndrome (MTS) in the population of patients with Lynch syndrome (LS) confirmed by genetic analysis. Other aims include describing the dermatological clinical manifestations of these patients in order to describe any possible new cutaneous manifestations of this syndrome. Another aim is to use molecular biology (microsatellite instability) and immunohistochemistry to analyze non-sebaceous skin lesions and deep-seated tumors that do not belong to the narrow spectrum of Lynch syndrome, and determine whether their occurrence in these patients is related to the genetic syndrome. The follow-up of these tumors (screening for new tumors) in patients with SL, as recommended by the learned societies, will also be evaluated. Finally, a biobank of cutaneous and deep tumour lesions in paraffin (retrospective) and smears of cutaneous lesions and healthy tissue (prospective) will be set up.

Familial Investigations of Childhood Cancer Predisposition

NOTE: This is a research study and is not meant to be a substitute for clinical genetic testing. Families may never receive results from the study or may receive results many years from the time they enroll. If you are interested in clinical testing please consider seeing a local genetic counselor or other genetics professional. If you have already had clinical genetic testing and meet eligibility criteria for this study as shown in the Eligibility Section, you may enroll regardless of the results of your clinical genetic testing. While it is well recognized that hereditary factors contribute to the development of a subset of human cancers, the cause for many cancers remains unknown. The application of next generation sequencing (NGS) technologies has expanded knowledge in the field of hereditary cancer predisposition. Currently, more than 100 cancer predisposing genes have been identified, and it is now estimated that approximately 10% of all cancer patients have an underlying genetic predisposition. The purpose of this protocol is to identify novel cancer predisposing genes and/or genetic variants. For this study, the investigators will establish a Data Registry linked to a Repository of biological samples. Health information, blood samples and occasionally leftover tumor samples will be collected from individuals with familial cancer. The investigators will use NGS approaches to find changes in genes that may be important in the development of familial cancer. The information gained from this study may provide new and better ways to diagnose and care for people with hereditary cancer. PRIMARY OBJECTIVE: * Establish a registry of families with clustering of cancer in which clinical data are linked to a repository of cryopreserved blood cells, germline DNA, and tumor tissues from the proband and other family members. SECONDARY OBJECTIVE: * Identify novel cancer predisposing genes and/or genetic variants in families with clustering of cancer for which the underlying genetic basis is unknown.

Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

This phase IIb trial tests whether Tri-Ad5 in combination with N-803 works to prevent colon and other cancers in participants with Lynch syndrome. Each of the three injections in Tri-Ad5 vaccine contain a different substance that is in precancer and cancer cells. Injecting these substances may cause the immune system to develop a defense against cancer that recognizes and destroys any precancer and cancer cells that produce these proteins in the future. N-803 may increase immune responses to other vaccines. Giving Tri-Ad5 in combination with immune enhancing N-803 may lower the chance of developing colon and other cancers in participants with Lynch syndrome.

Menstrual Cup for Early Endometrial Cancer Detection in Lynch Syndrome

Study Goal: This pilot study wants to find out if using a menstrual cup can be a good, non-invasive way to collect samples from the lining of the uterus (called the endometrium) to help screen for endometrial cancer. This is especially important for women who have a higher chance of getting this cancer, such as those with a genetic condition called Lynch syndrome. Main Questions the Study Will Answer: 1. Can a menstrual cup collect enough uterine lining (endometrial tissue) for doctors to examine under a microscope? 2. Are the samples from the menstrual cup as useful for diagnosis as samples taken using the usual method (called an endometrial biopsy or EMB)? 3. Is using a menstrual cup at home easy, effective, and comfortable for participants? 4. Can scientists grow small lab models of the uterus (called organoids) from the menstrual cup samples and from biopsy samples? What Will Happen in the Study: * Participants will use a menstrual cup at home to collect menstrual blood. * They will also have a standard endometrial biopsy done by a healthcare provider. * After both collections, participants will fill out a short survey about how comfortable and easy it was to use the menstrual cup. What the Study Will Measure: * Feasibility: How well participants are able to use the menstrual cup and send in the sample. * Sample Quality: Whether the menstrual cup collects enough good-quality tissue for testing, and how it compares to biopsy samples. * Participant Experience: How women feel about using the menstrual cup, based on the survey. * Lab Testing: Whether researchers can successfully grow endometrial organoids from both types of samples. Why This Study Matters: If this method works, it could offer a gentler, more convenient way for women to get checked for endometrial cancer-especially those who need regular screening. It could also make it easier to collect samples for research and improve early detection of cancer.

Testing the Combination of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) in Children, Adolescent, and Young Adult Patients With Relapsed/Refractory Cancers That Have an Increased Number of Genetic Changes, The 3CI Study

This phase Ib trial investigates the side effects of the combination of nivolumab and ipilimumab, and to see how well they work in treating patients with cancers that have come back (relapsed) or does not respond to treatment (refractory) and have an increased number of genetic changes. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tumor mutational burden (TMB) is the total amount of genetic changes or "mutations" found in tumor cells. Some studies in adults with cancer have shown that patients with a higher TMB (an increased number of genetic changes) are more likely to respond to immunotherapy drugs. There is also evidence that nivolumab and ipilimumab can shrink or stabilize cancer in adult patients with cancer. This study is being done to help doctors learn if the combination of nivolumab and ipilimumab can help children, adolescents, and young adults patients live longer.

Colonoscopy Check-up in People With Lynch Syndrome

Lynch syndrome, an inherited condition, increases bowel cancer risk. People with Lynch syndrome are recommended to have regular colonoscopies where a camera in a tube is used to look inside the bowel for cancer and for polyps (growths that sometimes can become cancerous). UK guidelines recommend that people with Lynch syndrome have colonoscopy check-up every 2 years after reaching a certain age; however, they face many challenges which make it difficult to have the recommended check-up. Among a subset of people with Lynch syndrome in England, this study investigated the: * percentage who underwent colonoscopy check-up as recommended by UK guidelines * factors influencing whether a person is more/less likely to have the recommended colonoscopy check-up * views, experiences, and challenges of living with Lynch syndrome and undergoing colonoscopy check-up This study collected information from people in the 'Lynch syndrome research registry pilot' using a questionnaire. The Cancer Screening and Prevention Research Group (CSPRG) at Imperial College London set up the Lynch syndrome research registry pilot, which included adults with Lynch syndrome who had previously participated in the Cancer Prevention Programme 3 (CaPP3) trial. The present study included people who took part in the Lynch syndrome research registry pilot, provided consent to be contacted about future research, and were aged ≥25 years. People who had undergone surgery to remove their rectum were excluded. The investigators used the 'Views, experiences, and challenges of colonoscopy check-up questionnaire', together with a few pieces of additional information previously collected as part of the Lynch syndrome research registry pilot. Participation involved completing the questionnaire only. The study was completed over approximately one year from administering the questionnaire in January 2024 to sharing results with participants in December 2024.

A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome

To learn about the effects of naproxen and aspirin on the normal colon in people with Lynch Syndrome.

Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers

The primary objective is to assess the effect of vaccination with neopeptide-loaded dendritic cells on disease-free survival (DFS) compared to placebo in LS subjects who are known to be carrier of a germline MMR-gene mutation with no signs of disease.

Collecting Blood and Stool Samples to Detect Colorectal Cancer or Advanced Neoplasia in Lynch Syndrome Patients

This study collects blood and stool samples from patients with suspected or diagnosed Lynch syndrome to evaluate a deoxyribonucleic acid (DNA) screening technique for the detection of colorectal cancer in Lynch syndrome patients.

A Web-Based Program (Kindred) to Improve the Understanding of Genetic Cancer Risk and Cancer Genetic Testing in African American Families

This clinical trial studies whether a web-based program, Kindred, works to improve the understanding of genetic cancer risk and cancer genetic testing in African American families. Between 5% and 10% of all cancers are caused by genetic changes that are hereditary, which means that they run in families. Some kinds of cancer or a family history of cancer means individuals are more likely to have a genetic change. If a genetic change is identified in a family, other relatives can choose to undergo hereditary cancer genetic testing to better understand their cancer risk. In families where a genetic change is not identified, or results are uncertain, relatives may also benefit from discussing their cancer risk with providers and, in some cases, getting hereditary cancer genetic testing themselves. Research has shown that African Americans are less likely than other racial groups to engage in cancer genetic testing. Kindred is an online tool that provides information so individuals can learn about their cancer genetic test results, how cancer genetic testing can help individuals and families understand their overall cancer risk (and strategies for reducing risk), and ways to talk with each other about cancer risk and health. This may be an effective way to improve the understanding of genetic cancer risk and cancer genetic testing in African American families.

Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland

Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland and affect more than 12,000 individuals annually. Several hundred of these patients are likely to carry known genetic mutations associated with HBOC or LS. Genetic testing for hereditary susceptibility to cancer can prevent many cancer deaths through early identification and engagement in high-risk management care that involves intensive surveillance, chemoprevention and/or prophylactic surgery. However, current rates of genetic testing indicate that many Swiss mutation carriers and their family members do not use cancer genetic services (counseling and/or testing), either due to lack of coordination of care or due to lack of communication about the mutation among family members. Cascade screening identifies and tests family members of a known mutation carrier. It determines whether asymptomatic family members are carriers of the identified mutation and proposes management options to reduce harmful outcomes. Robust evidence of basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for HBOC and LS. However, translation of this knowledge into public health interventions is lacking. Specific Aims of the CASCADE study are: 1. Survey Index Patients diagnosed with HBOC or LS from clinic-based genetic testing records and determine their cancer status and surveillance practices; needs for coordination of medical care; psychosocial needs; patient-provider and patient-family communication needs; quality of life; willingness to serve as advocates for cancer genetic services for blood relatives. 2. Survey first- and second-degree relatives, and first cousins identified from pedigrees and/or family history records of HBOC and LS Index Patients and determine their cancer and mutation status; cancer surveillance practices; needs for coordination of medical care; barriers and facilitators to using cancer genetic services; psychosocial needs; patient-provider and patient-family communication needs; quality of life; willingness to participate in a study designed to increase use of cancer genetic services. 3. Explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and blood relatives.

Impact of Consumption of Ultra-processed Foods in Individuals at High Risk of Cancer

The U-TRANS study was initiated by Gustave Roussy, which is its sponsor\*. It is part of the Interception Program and aims to reduce the consumption of ultra-processed foods in order to improve the overall quality of the diet among people at high risk of cancer (WCRF score ≤ 5, corresponding to low adherence to nutritional cancer prevention recommendations: eating a diet rich in whole grains, vegetables, fruit and fibre, and limiting ultra-processed foods, red meat, processed meats, sugary drinks and alcohol). It assesses the impact of a digital intervention (based on the use of the Open Food Facts app) as a complement to the nutritional education provided by the Interception program.

Preventive Dendritic Cell Vaccination for Lynch Syndrome

The aim of this study is to assess safety, feasibility and immunogenicity of vaccination with neopeptide-loaded dendritic cells in Lynch Syndrome subjects who are known to be carrier of a germline MMR-gene mutation without signs of disease.

Evaluation of Capsule Colonoscopy in Patients With Lynch Syndrome

Lynch syndrome is the most common hereditary cancer syndrome and is caused by pathogenic variants in DNA mismatch repair genes, resulting in a markedly increased lifetime risk of colorectal cancer. The estimated lifetime risk of colorectal cancer varies by the affected gene and is approximately 54-74% in men and 30-52% in women with Lynch syndrome. Colorectal cancer in this population is typically diagnosed at a younger age than in the general population. Current national guidelines recommend colonoscopic surveillance every one to two years beginning at 20-25 years of age to reduce colorectal cancer risk. However, individualized modification of surveillance strategies is under active consideration based on factors such as the specific mutated gene, family history of cancer, smoking status, prior malignancies, and age at surveillance initiation. Conventional colonoscopy, the current standard method for colorectal evaluation, may cause substantial discomfort or anxiety, leading some patients to decline participation. Colonoscopy is also resource intensive, and procedural capacity is limited. Previously reported limitations in colonoscopy resources and quality in Sweden highlight the need to evaluate alternative surveillance and screening approaches. Colon capsule endoscopy (CCE) has been available for clinical use since 2006 as a non-invasive alternative to colonoscopy, enabling endoscopic visualization of the entire colon. The system consists of a single-use, swallowable capsule containing miniature cameras that capture images as the capsule progresses through the gastrointestinal tract via natural peristalsis. Images are transmitted wirelessly to a portable data recorder worn by the patient and subsequently reviewed using dedicated software. CCE offers several advantages compared with conventional colonoscopy and CT colonography, including no requirement for sedation, endoscope insertion, gas insufflation, or ionizing radiation. The examination and image acquisition can be performed outside the hospital setting. This patient-centered approach has the potential to improve adherence to repeated examinations and long-term surveillance programs, which is particularly important for individuals with hereditary colorectal cancer syndromes. CCE may also reduce demands on healthcare resources. International guidelines indicate that the mucosal diagnostic performance of CCE is comparable to that of standard colonoscopy and that the method is appropriate for screening purposes. Adequate bowel preparation is required for both colonoscopy and CCE. Unlike conventional colonoscopy, bowel cleansing cannot be optimized during CCE, and the procedure is limited by capsule battery life, typically 10-12 hours. To maintain bowel cleanliness and facilitate capsule transit, patients administer laxative and prokinetic agents at predefined time points during the examination. The primary objective of this study is to evaluate the diagnostic performance and safety of colon capsule endoscopy as a first-line surveillance modality in patients with Lynch syndrome and to assess patient experience and acceptance of CCE compared with conventional colonoscopy.

Lynch Syndrome X-Talk of Enteral Mucosa With Immune System

Lynch syndrome (OMIM #120435) is the most common dominantly inherited colorectal cancer syndrome with an estimated prevalence of 1:270 individuals. It increases the lifetime risk of colorectal and endometrial cancer primarily, but it is associated with a high risk of other cancers (pancreas, stomach, ovarian, central nervous system, skin, among others). It is caused by a germline mutation in one of four DNA mismatch repair genes or a terminal deletion of the MSH2-adjacent gene EpCAM. Despite adherence to cancer surveillance programs, many patients still develop colorectal cancer and endometrial cancer. The Prospective Lynch Syndrome Database (PLSD) suggests that more frequent surveillance intervals do not significantly improve cancer risk reduction. The PLSD also revealed that the incidence of colorectal cancer in MLH1 and MSH2 carriers was even higher than previously expected, reaching as high as 41-36% among MLH1 carriers, regardless of ethnic background. The development of colorectal cancer despite surveillance is an unresolved question. Therefore, there is an unmet need for effective cancer prevention strategies.

Videocapsule Endoscopy in Lynch Syndrome

Background Lynch syndrome is caused by a pathogenic variant in one of the four Mismatch Repair genes (MMR): MLH1, MSH2/Epcam, MSH6, or PMS2. These pathogenic variants confer a higher risk of developing colorectal and other cancers, including small bowel cancer. The risk of developing a small bowel adenocarcinoma is about 100 times higher compared to individuals without Lynch syndrome, and the lifetime risk of small bowel cancer is estimated at 4,2%. The diagnosis of a small bowel cancer depends on videocapsule endoscopy (VCE). This device is swalled so that it can record images of the small bowel, which are then stored on a wearable device for about 8 hours. The capsule is then expelled in the feces while the images are transferred to a computer to be analysed. To date, there is conflicting evidence on the efficacy of small bowel cancer screening with VCE Rationale: this registry study will collect prospective data from patients with LS undergoing VCE Aim: evaluate the incidence of neoplastic and pre-neoplastic lesions in patients with LS during a VCE-based small bowel cancer screening study Design: this is a multicentric, observational study that analyzes data from diagnostic techniques already approved. Patients will not undergo diagnostic procedures beyond what would be recommended by clinical practice.

The Yield of Artificial Intelligence (GI Genius) in Lynch Syndrome - A Randomized Tandem-colonoscopy Trial

We aim to investigate the incremental detection rate of polyps using AI- assisted colonoscopy compared with high-definition white-light endoscopy (HD-WLE). We will conduct a single-center randomized tandem colonoscopy trial of patients with Lynch syndrome with and without AI. Patients will undergo tandem colonoscopy, the second colonoscopy with either HD-WLE or an AI- assisted device.

Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families

This trial studies how well weight management and health behavior intervention works in helping patients with hereditary breast and ovarian cancer and Lynch syndrome mutation carriers lose or maintain a healthy weight and lower their risk for cancer. Lifestyle behaviors such as physical activity, diet, and weight management may play a key role in preventing cancers and improving outcomes even in those with hereditary cancer syndromes.