Memorial Sloan Kettering

Researchers are studying how women with pathogenic variants in breast cancer predisposition genes such as BRCA1, BRCA2, ATM, CHEK2, and PALB2 respond to genetic risk modifier testing. The study aims to understand how these women make healthcare decisions based on their genetic test results. It focuses on women aged 25 years or older who have no personal history of breast cancer and are English-fluent. Participants will provide saliva and buccal swab samples for genetic risk modifier testing and complete a series of questionnaires at specific time points. The study includes an initial assessment at enrollment, a follow-up assessment about one week later, and a final assessment six months after receiving their test results. Participants are encouraged to complete these questionnaires electronically through a secure system. During the study, participants will be contacted to complete questionnaires that explore their reactions and decision-making processes after genetic testing. Researchers will monitor choices such as opting for preventive mastectomy or pursuing surveillance over a three-year period. Data collection is through questionnaires and genetic samples, with the total participation time spanning several months with scheduled assessments.

Researchers are studying how BRCA gene mutations affect the ovaries in premenopausal women, especially those with early-stage breast cancer or at high genetic risk. The study aims to understand how these mutations may influence fertility and the timing of early menopause by measuring hormone levels and collecting health information over time. Participants will have blood samples taken to measure hormones such as anti-Mullerian hormone AMH, estradiol, and follicle stimulating hormone FSH before, during, and after cancer treatment or observation. They will also complete questionnaires about their menstrual cycles, reproductive health, and sexual function. Follow-ups include monthly menstrual calendars and annual questionnaires for up to three years. During the study, women will attend multiple visits for blood draws and to provide health information. Researchers will monitor changes in hormone levels and menstrual patterns to assess ovarian reserve and reproductive health. The main outcome is to track changes in AMH levels from the start to one year after chemotherapy or hormonal therapy. Safety and health status will be observed throughout, with total participation lasting up to two years or more depending on follow-up.

Researchers are studying malignant colorectal polyps to understand the risk of cancer remaining, returning, or spreading after the polyp is removed. The study also aims to learn how patients and doctors decide on further treatment following the removal of a malignant polyp. This observational study collects detailed medical information to better understand disease outcomes over time. Participants have had a malignant polyp removed by endoscopic methods such as simple snare polypectomy, conventional endoscopic mucosal resection, or endoscopic submucosal dissection. The study involves collecting medical records, test results, imaging scans, lab work, pathology reports, colonoscopy images, and pathology slides related to the polyp. There are no experimental treatments or drugs involved. During the study, researchers will follow participants health through regular doctor visits and phone contacts at 1, 3, and 5 years after joining. The main measure is the risk of residual or recurrent disease within 5 years. This long-term follow-up helps monitor outcomes and gather information on patient health and treatment decisions over time.

Researchers are studying genetic changes in cancer cells, focusing on mutations that may influence how cancer cells survive. The study aims to test cancer tumors for specific gene mutations using leftover tissue from prior surgeries or biopsies. Additionally, participants provide blood, cheek swab, or saliva samples to compare normal genes with tumor mutations. This observational study seeks to understand how tumor genes change over time and affect responses to experimental cancer treatments. The study includes molecular profiling of tumors through leftover or prospectively collected tissue samples analyzed in a certified laboratory. It also involves clinical germline analysis of normal DNA samples to detect inherited mutations linked to cancer risk. Participants in Part B may undergo minimal risk collections and research biopsies. The study uses advanced sequencing techniques such as whole genome and exome sequencing and examines genetic mechanisms of tumor development. Participants provide tumor tissue and normal gene samples, which are tested using various genetic assays. The team assesses the frequency of actionable mutations and evaluates how molecular profiling results influence patient treatment. Data is collected over time to explore genetic changes and tumor behavior. Safety and impact are monitored through research biopsies and clinical follow-up, with the study continuing until January 2027.

Researchers are evaluating the effects of pembrolizumab alone compared to the standard treatment of chemotherapy cisplatin or carboplatin combined with radiation therapy after surgery in patients with recurrent or second primary head and neck squamous cell carcinoma. This phase II trial aims to assess overall survival, disease control, metastasis rates, and side effects in high-risk patients, while also exploring whether high PD-L1 expression predicts better responses to pembrolizumab. Participants are randomly assigned to one of two treatment groups. One group receives intravenous cisplatin or carboplatin weekly for six cycles alongside daily intensity-modulated radiation therapy or proton beam radiation totaling 30 sessions. The other group receives intravenous pembrolizumab every six weeks for up to nine cycles. Throughout treatment, participants undergo CT or MRI scans to monitor their condition. After completing treatment, participants are followed up 30 days later and then every six months for up to five years. During the study, researchers evaluate overall survival from randomization to death, adverse events for up to five years, disease-free survival, and PD-L1 expression levels. The study monitors patients closely with imaging and clinical assessments to track treatment effects and safety over time.

Researchers are evaluating the safety and effectiveness of the study drug Ado-trastuzumab emtansine T-DM1 combined with standard chemoradiation in treating HER2-positive salivary gland cancer. This phase II study focuses on how well T-DM1 works to prevent cancer recurrence after surgery and its safety when used alongside radiation and chemotherapy. Participants will receive standard surgery followed by radiation and chemotherapy with added T-DM1 treatment. T-DM1 is given through an intravenous infusion once every three weeks at a set dose for up to one year. Radiation and chemotherapy are scheduled during the first three cycles, with radiation and chemotherapy administered on specific days within these cycles. After treatment, participants will be followed for two years. Throughout the study, participants will undergo screening, evaluations, and follow-up visits including tests of organ function, cardiac assessments, and blood work. Researchers will monitor disease-free survival over two years, adverse events, overall survival, and distant metastasis-free survival up to three years. The total participation includes treatment for about one year and follow-up for up to three years.

Researchers are investigating targeted therapies directed by genetic testing for patients with locally advanced or advanced solid tumors that have spread or progressed after standard treatments. This Phase 2 screening trial, called ComboMATCH, aims to match patients to specific combination treatments based on genetic mutations found in their tumor cells. The study seeks to improve treatment planning by using genetic information to guide therapy choices. Patients undergo tumor genetic screening using previously collected samples or a new biopsy if eligible and aged 18 or older. Based on their tumors genetic profile, patients are assigned to one of multiple treatment subprotocols involving different drug combinations. Treatments include oral, intravenous, and intramuscular drugs such as selumetinib, olaparib, fulvestrant, binimetinib, and others. Treatment cycles generally repeat every 28 days until disease progression or unacceptable toxicity. Patients may also undergo biopsies, blood collection, imaging scans CT, MRI, PET, echocardiograms, and bone marrow procedures as part of the study. Throughout the trial, participants have regular assessments including tumor biopsies, blood draws, imaging tests, and heart function monitoring. These evaluations occur during screening, treatment, and follow-up periods. Researchers measure patient enrollment, assignment to treatment arms, and treatment outcomes over up to 8 years. Safety is monitored via clinical evaluations and diagnostic tests. This comprehensive approach aims to evaluate responses to targeted therapies guided by tumor genetics for advanced solid tumors.

Researchers are investigating the combination of axitinib and nivolumab as a treatment for people with advanced or metastatic mucosal melanoma that has not received prior treatment. This study aims to evaluate whether using these two drugs together can better target proteins that help cancer cells survive and grow compared to using them separately. This is a phase 2 trial focusing on unresectable locally advanced or metastatic mucosal melanoma. Participants will receive nivolumab intravenously every 4 weeks along with axitinib taken orally twice daily. If the disease progresses but the patient tolerates treatment well, additional therapies may be added depending on progression type. For local or limited progression, stereotactic body radiation therapy SBRT will be given, and for more widespread progression or prior radiation sites, ipilimumab will be added intravenously every 3 weeks for up to four doses. The maximum duration for combined nivolumab and axitinib therapy is 104 weeks. During the study, patients will be regularly monitored through imaging to measure tumor response and other clinical assessments. The primary outcome measured is the best objective response within one year. Patients blood tests and organ functions will be evaluated to ensure safety, and those who progress on the initial treatment may be screened to join the triplet therapy phase. The total duration and timing of treatments and follow-ups will be carefully tracked throughout the trial.

Researchers are evaluating dose-escalated radiation therapy compared to usual care for patients with locally advanced unresectable pancreatic ductal adenocarcinoma who have already completed 4 to 6 months of chemotherapy. The study is a phase III trial aiming to determine if higher doses of radiation can improve 3-year overall survival, as well as assess effects on tumor progression, chemotherapy-free intervals, treatment toxicity, and quality of life. This trial is led by NRG Oncology and focuses on patients without disease progression after initial chemotherapy. Participants are randomly assigned to one of two groups. The first group receives standard care, which may include additional chemotherapy options such as FOLFIRINOX, NALIRIFOX, or gemcitabinenab-paclitaxel, standard radiation therapy with concurrent chemotherapy, or observation. The second group receives dose-escalated radiation therapy delivered in either 5 or 25 fractions, with or without concurrent chemotherapy for the 25-fraction option. After radiation, patients who have not completed 6 months of chemotherapy are encouraged to finish it, with treatment beyond 6 months at the physicians discretion. Imaging and tissue biopsies are performed throughout the study. Participants undergo various assessments including blood sample collection, CT scans, MRI, and optional PETCT scans before and during treatment. Tumor tissue biopsies are also collected. Follow-up visits occur every 3 months for the first 2 years and annually for an additional 3 years. Researchers measure overall survival, local disease progression, progression-free survival, chemotherapy-free intervals, and adverse events. Quality of life is evaluated using specific questionnaires over the course of participation.

This research aims to evaluate the safety, side effects, and best dose of SM08502 cirtuvivint alone and combined with ASTX727 in patients with acute myeloid leukemia AML and myelodysplastic syndromes MDS. The study focuses on relapsed or refractory AML and MDS, as well as frontline high-risk MDS. Cirtuvivint may work by blocking enzymes needed for cancer cell growth, while ASTX727 combines decitabine and cedazuridine to help bone marrow produce normal blood cells and kill abnormal cells. This phase I trial explores how these treatments affect patients, including their safety and potential anti-tumor activity. Participants are divided into three groups receiving different schedules of oral cirtuvivint Cohort I receives the drug daily on days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle Cohort II receives it on days 1, 4, 8, 11, 15, 18, 22, and 25 and Cohort III receives the same cirtuvivint schedule as Cohort II plus ASTX727 on days 1-5. These cycles repeat every 28 days unless disease progression or unacceptable toxicity occurs. Before treatment, patients undergo heart function tests echocardiography or MUGA scan and blood and bone marrow sample collections. During the study, patients continue blood and bone marrow sampling to monitor their response and safety. After treatment, they are followed for 30 days, then every three months for two years, and every six months for up to three more years. Researchers measure the maximum tolerated dose, recommended phase 2 dose, adverse events, clinical response, event-free survival, and overall survival. This comprehensive monitoring helps evaluate the treatments effects and guide future development.