Barrett Esophagus

Researchers are evaluating the long-term outcomes of stopping endoscopic surveillance in patients with low-risk non-dysplastic Barrett's esophagus (NDBE). This observational study aims to determine whether discontinuing surveillance leads to an increase in clinically significant esophageal adenocarcinoma (EAC), focusing on patients with Barrett's esophagus less than 5 cm in length, no history of dysplasia, and no family history of EAC. The study is a nationwide, prospective, single-arm project in the Netherlands with a minimum follow-up duration of 10 years. In this study, endoscopic surveillance is discontinued following new Dutch guideline recommendations for eligible low-risk NDBE patients. Participants are then monitored through existing national registries and medical records without additional procedures or interventions. Two patient groups will be analyzed separately: those with prior surveillance history and those newly diagnosed with NDBE at inclusion. Data collection involves pathology reports, national statistics, and cancer registries, with outcomes reviewed annually by a data safety monitoring board. Participants provide informed consent to be included in the registry, but no active involvement or changes to their care are required beyond standard practice. Researchers will track the incidence of clinically apparent EAC, defined by EAC-related death or EAC requiring palliative or non-curative treatments, over at least 10 years. Privacy protections and ethical standards are carefully maintained throughout the study to minimize risks and ensure confidentiality.

Researchers are investigating the development of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's Esophagus (BE). This study compares the traditional random biopsy method with a new Wide-Area Transepithelial Brush-Sampling (WATS) technique to improve detection during surveillance. The study focuses on two groups: those at high risk after removal of visible lesions or low-grade dysplasia and those under routine BE surveillance without dysplasia. Participants will undergo baseline and follow-up endoscopies over three years where both random biopsies and WATS brushings are performed. The WATS brush samples cells from all epithelial layers using a specialized cytology brush passed through the endoscope. This method is being studied for its potential to detect dysplasia earlier and more thoroughly than traditional biopsies. Samples collected will also support future biomarker research to better predict disease progression. During the study, participants will have regular endoscopic exams with combined biopsy and brush sampling to monitor for the appearance of HGD or EAC. Researchers will analyze biopsy results, WATS findings, and patient outcomes over the three-year follow-up. Safety and procedure effectiveness will be assessed, and the study allows for specimen collection to explore new diagnostic markers. The total participation duration is three years, with ongoing monitoring to understand the natural history of cases identified by WATS but not by biopsy.

Researchers are evaluating DISP-10, a combination therapy made up of DV-10 (an adenovirus) and idecabtagene vicleucel (ide-cel, a BCMA-directed CAR T cell therapy), in adults with advanced gastrointestinal cancers. This Phase 1, multicenter, open-label study aims to assess the safety, tolerability, and potential effectiveness of DISP-10 in people with advanced or metastatic colorectal, gastric, esophageal, or gastroesophageal adenocarcinoma. The study is sponsored by Dispatch Biotherapeutics and is divided into two parts: dose-escalation and dose-expansion. Participants will receive DISP-10, which involves leukapheresis to collect blood cells for ide-cel production. During this process, bridging therapy may be given as needed for disease control. Before ide-cel infusion, patients will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The first part of the study focuses on finding the recommended dose for expansion by testing increasing doses of DISP-10, while the second part evaluates safety and effectiveness at this dose. During the study, participants will be closely monitored for treatment-related side effects, dose-limiting toxicities, and overall response to therapy for up to two years. Researchers will assess outcomes such as disease control, duration of response, progression-free survival, and overall survival, with some follow-up extending up to fifteen years. Safety monitoring includes tracking adverse events for 90 days, and serious adverse events related to the treatment will be observed for two years.

Researchers are evaluating NRM-823, a bispecific T-Cell Engager drug, in adults with locally advanced or metastatic solid tumors that are refractory to treatment. The study focuses on cancers including non-small cell lung cancer, triple negative breast cancer, head and neck squamous cell carcinoma, esophageal and gastric adenocarcinomas, cervical, endometrial, and ovarian cancers. The trial aims to assess the safety and tolerability of NRM-823 alone and in combination with an immune checkpoint inhibitor. The study is divided into three parts. Part A evaluates the safety and tolerability of NRM-823 alone to identify a recommended dose. Part B further assesses safety and tolerability of that dose in a larger group of participants. Part C investigates the safety and tolerability of NRM-823 combined with a checkpoint inhibitor. Treatments are administered according to protocol requirements throughout these phases. Participants will be monitored from enrollment until 30 days after their last dose for treatment-emergent adverse events and dose-limiting toxicities. The study includes assessments of liver, kidney, lung, heart, and blood function to ensure safety. Participants will be followed closely to evaluate how their bodies tolerate the treatment and to gather information on side effects during and after the treatment period.

Researchers are evaluating a new combination therapy using tislelizumab and FLOT chemotherapy given before surgery (neoadjuvant) for patients with locally advanced, resectable adenocarcinoma of the esophagus or stomach. This phase Ib trial aims to determine if this combination is safe and active enough to support further studies of new drug combinations in this setting. The study also explores extending preoperative chemotherapy cycles to improve patient tolerance compared to the usual pre- and postoperative schedule. The treatment involves two dose levels in a dose intensification phase: Dose level 1 includes 4 cycles of tislelizumab (200 mg intravenously every 3 weeks) combined with 6 cycles of FLOT chemotherapy (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil intravenously every 2 weeks). Dose level 2 increases to 5 cycles of tislelizumab plus 8 cycles of FLOT. The optimal dose level, where side effects are acceptable, will then be expanded with additional patients. The study focuses on giving more cycles before surgery to assess safety and potential clinical activity. Participants will be monitored closely during treatment for side effects and effectiveness, with assessments including physical exams, blood tests, and imaging. Researchers will measure the feasibility of delivering up to 8 months of this combined therapy before surgery. The trial will also involve checking tumor tissue for specific markers to guide treatment evaluation. The total duration includes the treatment phase and follow-up to assess patient outcomes and safety.

Esophageal cancer, including esophageal adenocarcinoma, squamous cell carcinoma, and gastroesophageal junction carcinoma, has a low five-year survival rate under 20% and is becoming more common. Researchers are studying whether adding itraconazole, an antifungal medication that blocks certain cancer growth pathways, to the usual treatment of chemoradiation and surgery can improve outcomes. This phase II trial aims to see if itraconazole increases the rate of complete tumor disappearance after treatment in patients with resectable esophageal or gastroesophageal junction cancer. Patients will first have standard cancer staging with PET/CT scans and endoscopic ultrasound to check for spread. If no distant cancer is found, they will take oral itraconazole twice daily for two weeks before starting standard neoadjuvant chemoradiation. After completing chemoradiation, patients will continue itraconazole for 6 to 8 weeks. Following treatment, if scans show no new metastases, patients will undergo surgery to remove the esophagus. Throughout the study, itraconazole levels and side effects will be monitored to assess adherence and safety. Participants will have tissue samples collected before and after treatment to analyze the activity of cancer growth pathways and measure drug levels. Blood samples will also be tested for circulating tumor DNA and exosomes as markers of response. The main outcome is the rate of pathologic complete response at about 20 weeks. Secondary goals include correlating drug levels with outcomes and developing genetic profiles to predict treatment response. This study lasts from initial staging through surgery and follow-up assessments.

Researchers are evaluating new treatment options for Barrett's Esophagus, a condition where the esophageal lining changes and carries a risk of progressing to precancerous stages or cancer. The study compares a new mechanical resection technique using the EndoRotor device against the current standard treatment of thermal destruction by radiofrequency ablation. This comparison aims to find a potentially more effective and cost-efficient method for eradicating Barrett's Esophagus, especially in cases complicated by dysplasia or superficial adenocarcinoma. The study involves two treatment groups: one receiving the EndoRotor procedure, which mechanically removes the entire mucosal surface in a single session, allowing tissue collection for analysis; the other receiving thermal ablation with the HALO system using radiofrequency energy applied after mucosal cleaning. Each technique has specific procedural steps and devices used. The EndoRotor treatment includes submucosal injection to reduce risks, followed by mucosal resection and tissue aspiration. Radiofrequency treatment involves sizing the esophagus and applying energy via specialized probes to destroy the abnormal mucosa. Participants will undergo endoscopic evaluations before and after treatment, with biopsies taken to assess the presence or absence of Barrett's Esophagus and dysplasia at 3 and 12 months. Safety assessments include monitoring discomfort, pain, dysphagia, adverse events, and esophageal narrowing after treatment. Researchers will also evaluate the quality of tissue analysis from EndoRotor samples and economic outcomes such as cost-effectiveness. The study continues through follow-up visits up to 12 months post-treatment to measure treatment success and safety.

Researchers are studying Barrett's Esophagus and early esophageal cancer to prepare for a larger future study. The study aims to collect tissue samples from the esophagus and blood to analyze genetic markers using new high-throughput methods. It also evaluates the quality of life and fear of cancer in patients with Barrett's Esophagus, focusing on those referred for suspicion of high-grade dysplasia or early cancer. Participants will undergo two routine endoscopies during which standard biopsies and blood samples will be taken, along with additional samples specifically for the study. These include cells collected by brush cytology from the esophagus and up to ten tissue samples from the esophagus and stomach. The extra procedures extend the endoscopy by about 10-15 minutes. The study involves three contacts: one screening visit and two sample collections during scheduled care. During the study, participants will complete questionnaires on quality of life and cancer worry at three different times using their mobile phones. Researchers will monitor the success of sample collection and genetic analysis over 6 to 24 months. Patient outcomes will be followed for up to five years through routine care visits without requiring extra visits. The study is sponsored by University Hospital, Antwerp.

Researchers are evaluating KK2269, a new intravenous drug, in adult participants with advanced or metastatic solid tumors for which no standard therapy is available. This first-in-human, multicenter, open-label, non-randomized study has two parts. Part 1 focuses on assessing the safety and tolerability of KK2269 alone in various solid tumors. Part 2 enrolls participants with gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, esophageal adenocarcinoma, or non-small cell lung cancer (NSCLC) who have had at least one prior systemic therapy, to assess KK2269 combined with docetaxel. In Part 1, KK2269 is given by intravenous infusion at escalating doses. In Part 2, KK2269 is administered intravenously in combination with docetaxel, which is given intravenously every three weeks. Participants in both parts who refuse standard therapy are also eligible. The study aims to determine recommended dose levels and intervals for the combination treatment in Part 2. Participants will undergo safety and tolerability assessments, with the primary outcomes including the number of subjects experiencing dose-limiting toxicity within 21 days after the first dose and adverse events throughout about one year of study completion. Patients must have measurable disease and good performance status. The trial includes regular monitoring by investigators, with follow-up for safety and adverse events throughout the study period.

Researchers are evaluating a new treatment called Mesothelin-targeted CAR T-cell therapy for people with mesothelin-positive esophagogastric adenocarcinoma who also have peritoneal carcinomatosis. This phase I trial aims to study the effects and safety of this therapy delivered directly into the abdomen. The study is sponsored by Memorial Sloan Kettering Cancer Center and focuses on patients with advanced cancer who have limited treatment options. Participants will have their white blood cells (T cells) collected through a procedure called leukapheresis. These cells will be modified in a lab to target mesothelin, a protein expressed on their tumors, creating the M28z1XXPD1DNR CAR T cells. The modified cells will then be infused back into the participant's abdomen. The therapy period will last about 3 to 4 weeks, during which different doses of the CAR T cells may be given to assess safety and dosage limits. Throughout the study, participants will undergo various assessments including imaging to evaluate tumor response, blood tests to monitor cell counts and chemistry, and tests for infectious diseases. Researchers will track treatment-related side effects for up to one year and determine the maximum tolerated dose of the CAR T cells. Participants must meet strict health criteria to ensure safety. The total participation time includes pre-treatment evaluations, treatment infusion, and follow-up monitoring to observe effects and safety outcomes.