Londonderry

This trial focuses on both women and men diagnosed with Stage I HER2-positive invasive breast cancer. It aims to compare two different combinations of HER2-targeted therapies given after surgery, studying how well each treatment controls the cancer and their side effects. The study is a randomized phase II trial supported by Genentech and led by the Dana-Farber Cancer Institute, evaluating long-term benefits and disease-free survival over several years. Participants are randomly assigned to one of two groups. One group receives six cycles of intravenous trastuzumab-emtansine T-DM1 every three weeks, followed by eleven cycles of subcutaneous trastuzumab every three weeks. The other group receives weekly intravenous paclitaxel for twelve weeks along with subcutaneous trastuzumab every three weeks, continuing trastuzumab alone for additional cycles. The entire treatment period lasts about one year. During the study, participants undergo screening and regular laboratory evaluations along with follow-up visits. Researchers monitor side effects, quality of life, symptoms related to therapy, and cardiac function. The main outcomes measured include the incidence of toxicities during the first 18 weeks and disease-free survival over up to 72 months. Participants are followed for five years after treatment to assess long-term outcomes and safety.

Researchers are investigating the long-term safety and effectiveness of Cardiac Contractility Modulation CCM therapy in people with heart failure. This global study combines both past and future patient data to observe how CCM therapy, delivered through Impulse Dynamics devices, performs in real-world settings over extended periods. The goal is to better understand CCM therapys impact on heart failure outcomes and any related device or procedure complications. The study includes patients who have already received or will receive CCM therapy using Impulse Dynamics systems, including future technologies like CCM-D. It is a single-arm observational study without experimental treatment groups, following patients for at least five years after their therapy. Patients are grouped into prospective, retrospective, and hybrid cohorts based on when they receive or received the CCM therapy. Participants will be monitored through regular follow-ups to assess hospitalization rates and length of stay due to heart failure, safety regarding device-related complications, and various clinical outcomes such as mortality, functional capacity, and heart remodeling. Additional evaluations include quality of life measurements using the Kansas City Cardiomyopathy Questionnaire and assessments of therapy compliance. The study duration allows detailed observation of CCM therapy effects and patient health over several years, up to at least five years.

Researchers are evaluating treatments for older adults aged 70 and above with advanced stage IIIB-IV non-small cell lung cancer that expresses PD-L1 in 1-49% of tumor cells. This phase III trial compares the effects of adding chemotherapy to immunotherapy with pembrolizumab against pembrolizumab alone. The study aims to assess improvements in overall survival, progression-free survival, response rates, toxicity, quality of life, and explore geriatric assessment factors and gut microbiome correlations. Participants are randomly assigned to one of two groups. Arm A receives pembrolizumab intravenously every 21 days for four cycles, followed by maintenance pembrolizumab every 21 or 42 days for up to two years. Arm B receives the same pembrolizumab schedule plus one of several chemotherapy regimens, including combinations of pemetrexed, carboplatin, nab-paclitaxel, or paclitaxel administered intravenously on different schedules for four cycles, followed by pembrolizumab maintenance. Imaging with MRI, CT, and PET scans is performed at baseline and throughout the trial. During the study, participants undergo regular assessments including imaging scans to monitor disease status, blood tests, and quality of life questionnaires. After treatment completion, follow-up visits occur every three months for up to two years and then every six months up to five years. Researchers measure overall survival as the primary outcome and also track progression-free survival, response rates, adverse events, and patient-reported quality of life. Safety and tolerability are closely monitored along with exploratory analyses of chemotherapy dose intensity and microbiome factors.

Researchers are evaluating how to best recommend chemotherapy for patients with Stage IIB, IIC, or Stage III colon cancer based on the presence or absence of circulating tumor DNA ctDNA after surgery. This Phase IIIII trial explores whether ctDNA status can help guide decisions about the need for adjuvant chemotherapy and identify the optimal chemotherapy regimen for those at high risk of recurrence. Circulating tumor DNA is a promising biomarker that may detect microscopic residual cancer cells that traditional methods might miss. Participants are assigned to groups based on their ctDNA results after surgery. Those without detectable ctDNA ctDNA- may undergo serial monitoring without treatment or receive different chemotherapy regimens such as mFOLFOX6 or CAPOX for 3 to 6 months. Patients with detectable ctDNA ctDNA who have a higher risk of recurrence are randomized to receive either standard chemotherapy regimens like mFOLFOX6 or CAPOX for 6 months or a more intensive regimen called mFOLFIRINOX for 6 months. Central ctDNA testing is performed using the Signatera test to guide these assignments. During the study, participants have blood samples collected for ctDNA testing and undergo imaging scans to check for cancer recurrence. Researchers assess disease-free survival, overall survival, and chemotherapy compliance over several years. The study includes monitoring for safety and treatment effects, with follow-up planned for up to 5 years after randomization. Participants health status, laboratory tests, and tumor markers are regularly evaluated throughout the treatment and follow-up periods.

Researchers are comparing two chemotherapy combinations for treating advanced, unresectable, or metastatic HER2 negative adenocarcinomas of the esophagus, gastroesophageal junction, and stomach. This phase III trial evaluates modified FOLFIRINOX fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan with or without nivolumab versus modified FOLFOX fluorouracil, leucovorin calcium, and oxaliplatin with or without nivolumab. Chemotherapy drugs act to stop tumor growth by killing cells or stopping division, and immunotherapy with nivolumab may affect the immune system to hinder tumor growth and spread. Participants are randomized into two groups one receives mFOLFIRINOX plus nivolumab as clinically indicated, and the other receives mFOLFOX plus nivolumab as clinically indicated. Treatments are administered intravenously. Throughout the study, participants undergo magnetic resonance imaging MRI, computed tomography CT scans, and may provide blood samples. Nivolumab is given as needed based on clinical assessment during the trial. Participants will be monitored up to 2 years from randomization for overall survival, with secondary measures including progression-free survival, response rates, duration of response, adverse events, and patient-reported outcomes collected at baseline and during treatment cycles. Safety and tolerability are evaluated, and exploratory analyses include biomarker assessments such as PD-L1 combined positive score and cell-free DNA. The trial includes regular imaging and clinical assessments to track disease status and treatment effects.

Researchers are evaluating whether simply observing patients after surgery is as effective as continuing pembrolizumab treatment in preventing cancer recurrence in people with early-stage triple-negative breast cancer TNBC who had a complete response after receiving chemotherapy plus pembrolizumab before surgery. This Phase III trial aims to determine if stopping pembrolizumab post-surgery can maintain recurrence-free survival while potentially improving quality of life and reducing treatment burden. Participants are randomly assigned to one of two groups after finishing chemotherapy with pembrolizumab and surgery. One group continues pembrolizumab intravenously every 3 or 6 weeks for 27 weeks. The other group undergoes observation without further pembrolizumab for the same period. Throughout the study, patients have tumor biopsies and blood collected, along with imaging such as mammography, breast ultrasound, or MRI during follow-up. Participants will be monitored for recurrence-free survival and overall survival for up to 10 years. The study also assesses adverse events, quality of life, financial impact, and work productivity at about 27 weeks after starting the assigned treatment or observation. Safety and treatment effects are tracked through biopsies, imaging, blood tests, and patient questionnaires during the study and follow-up.

Researchers are evaluating new software features designed to improve the Rhythmia Mapping System, a device used for electroanatomical mapping during catheter ablation procedures in patients with atrial or ventricular tachyarrhythmias. This observational study seeks to assess the performance of these next-generation software improvements by collecting and analyzing data during routine clinical care. The goal is to guide further development of the software features for future commercial use without affecting the current treatment. Participants undergo standard of care catheter-based endocardial mapping using the commercial Rhythmia Mapping System during their cardiac ablation procedures. While the procedure takes place, raw signals are streamed to an investigational Rhythmia Workstation running prototype software features. These new features are assessed in parallel but are not used by physicians to influence clinical decisions or treatment during the procedure. Throughout the study, participants receive their usual cardiac mapping and ablation care. Researchers collect feedback from physicians on the softwares performance during the procedure. Data from the investigational workstation is analyzed to evaluate the software without impacting patient care. The total participation duration aligns with the procedure day, and safety is maintained by not altering the clinical treatment process.

Researchers are investigating precursor hematological cancers, such as early myelodysplastic syndromes MDS, monoclonal gammopathy of undetermined significance MGUS, smoldering multiple myeloma, and other low-grade blood cancers. This study aims to understand the genetic and molecular changes that occur in these blood cancers and how they relate to disease progression and clinical outcomes. By analyzing these molecular alterations, scientists hope to improve prevention and treatment strategies for blood cancers. The study uses tissue samples already collected during participants clinical care, including blood, bone marrow, lymph nodes, urine, and other specimens. Additional samples may be collected for research purposes, such as a small blood sample or a gentle cheek swab to obtain normal cells for comparison. Researchers may create living cell lines from the tissue samples for future studies. Participant specimens and data may be stored securely and shared with research repositories to aid in further genetic research. Participants will not undergo extra clinical tests beyond their usual care but will be asked for permission to use their samples and clinical information. Follow-up visits will be conducted at regular intervals to monitor disease progression risk. The main outcome measured is identifying molecular changes in patients cells over a 10-year period. Throughout the study, privacy and confidentiality of participant information will be protected, and no additional risks beyond routine care are expected.

Researchers are evaluating the addition of pembrolizumab immunotherapy to standard chemotherapy for patients with stage IIA, IIB, IIIA, or IIIB non-small cell lung cancer NSCLC that has been completely removed by surgery. This phase III trial aims to compare disease-free survival and overall survival among different treatment approaches, including chemotherapy alone, chemotherapy followed by pembrolizumab, and chemotherapy combined with pembrolizumab. The study also assesses quality of life and adverse event rates in these patient groups. Participants are randomly assigned to one of three groups. One group receives only chemotherapy with observation afterward. The other two groups receive chemotherapy followed by pembrolizumab or chemotherapy combined with pembrolizumab. Chemotherapy involves one of four platinum doublet regimens administered every 21 days for four cycles, depending on the physicians choice. Pembrolizumab is given intravenously over 25-40 minutes, either after chemotherapy or alongside it, repeated every 21 days or every 6 weeks for multiple cycles. Patients also undergo heart ultrasound, MRI, CT scans, and blood sample collections as part of the study. During the trial, participants have regular medical assessments including imaging and blood tests to monitor their health. Follow-up visits occur 6 weeks after treatment, then every 3 months for 2 years, every 6 months for years 2-4, and annually up to 10 years from randomization. Researchers measure disease-free survival as the main outcome, tracking the time until cancer recurrence or death. They also evaluate overall survival, side effects, drug tolerability, and patient-reported quality of life over time.

Researchers are evaluating different dosing strategies of CDK46 inhibitors in patients aged 65 years or older with Hormone Receptor Positive HR and HER2-negative Metastatic Breast Cancer MBC. The study aims to compare the time patients remain on treatment using the standard approved dosing versus a titrated dosing approach that starts at a lower dose and increases if well tolerated. This Phase 3, randomized trial also explores patient-reported outcomes and baseline factors to help personalize treatment for older patients. Participants will choose either palbociclib or ribociclib as their CDK46 inhibitor and select an endocrine therapy partner, either an aromatase inhibitor or fulvestrant. They will be randomized to one of two groups Arm 1 receives the indicated dosing regimen starting at the full approved dose, while Arm 2 starts at a lower dose with potential escalation based on tolerance. Treatment cycles are 28 days long, with the CDK46 inhibitor taken daily for 21 days per cycle. Throughout the study, participants will be monitored for treatment duration, side effects, quality of life, dose adjustments, and healthcare use. Data will be collected up to 48 months, including patient questionnaires and clinical assessments to track tolerability and outcomes. Telehealth visits and remote consenting are permitted to facilitate participation. The study seeks to find dosing strategies that help older patients tolerate treatment longer and improve their clinical benefit.