Clinical Research Directory

Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma

Background: * Malignant mesothelioma is a malignancy arising from the mesothelial cells of the pleura, peritoneum, pericardium, or tunica vaginalis. * Mesothelioma accounts for 0.10% of deaths annually in the United States. Malignant pleural mesothelioma is the most common of these, comprising of 80% of the cases with an annual incidence of about 2,500 in the United States. * The median survival from diagnosis of pleural mesothelioma is approximately 12 months. The majority of patients present with stage III or IV disease with 85-90% of patients considered unresectable at diagnosis. * Peritoneal mesothelioma has a better prognosis than pleural mesothelioma; nevertheless, patients undergoing therapy for peritoneal mesothelioma have few well-studied treatment options due in large part to the rarity of the disease. * In addition to mesothelioma, mesothelin is highly expressed in several cancers, including pancreatic, biliary adenocarcinomas, gastric and ovarian cancers; mesothelin is also expressed in a significantly larger proportion of thymic carcinoma than thymoma. Objectives: -To allow sample acquisition for use in the study of mesothelioma. Eligibility: * All participants age greater than or equal to 2 years with malignant mesothelioma OR * All participants greater than or equal to 18 years with thymic carcinoma, pancreatic or biliary adenocarcinoma or lung, gastric or ovarian cancers or other solid tumor known to express mesothelin * Must be able and willing to provide informed consent if 18 or over; parent or guardian must be able and willing to provide consent for patients under the age of 18 Design: * Up to 1000 subjects will be enrolled. * Patients will be followed to determine the course of disease and to record any treatment received for mesothelioma. * Patients will undergo sampling of blood, urine, tumor and abnormal body fluids for tissue banking. * Studies which may be performed on banked material include genetic and genomic studies, establishment of cell cultures and immunologic studies.

Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma

Background: Mesothelioma is an aggressive cancer that grows in the linings of the body; this can include the membranes that line the heart, lungs, and internal organs. Mesothelin (MSLN) is a protein that appears in high numbers in many tumors, including mesothelioma. Researchers are developing a new treatment that collects a person s own immune cells (T cells); the T cells are genetically modified to target and kill tumor cells with high levels of MSLN. Objective: To test a new treatment (TNhYP218 CAR T cells) in people with solid tumors including mesothelioma. Eligibility: People aged 18 and older with solid tumors including mesothelioma that returned or spread after standard treatment. Design: Participants will be screened. A small piece of tissue will be cut from a tumor (biopsy). The sample will be tested to see if it has enough MSLN. Participants will undergo leukapheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. Participant s T cells will be modified in a lab to produce TNhYP218 CAR T cells. Participants will enter the hospital. For 7 days, they will receive drugs to prepare their bodies for the study treatment. TNhYP218 CAR T cells will be administered into a vein. Participants will remain in the hospital for at least 7 more days. After discharge, participants will have follow-up visits for 5 years. These visits may include imaging scans, blood and heart tests, and a new biopsy. Long-term follow-up will continue another 10 years....

Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

Background: Gastric cancers are cancers of the stomach. Hereditary ones are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. They want to learn about changes these cause in the body and about the genes involved. Objective: -To gather data about hereditary gastric cancer. Eligibility: * People at least 2 years old with personal or family history with a hereditary gastric cancer. * People at least 2 years old with gene changes that lead to such cancer or a lesion that may be hereditary. Design: * Participants will be screened in a separate protocol. * Participants will have: * Physical exam * Medical history * Blood tests * Scans * Photos of skin lesions and other findings * Gynecology consultation for women * Cheek swab (some participants) * For some participants, their relatives will be asked to join the study. * Some participants will be asked to allow the study to get stored tissue samples for relatives who have died. * Some samples will be sent to outside labs. All personal data will be protected. Samples will be destroyed when the study ends. * Participants will get the results of genetic testing. * Participants who cannot come to the NIH clinic may just give a cheek swab and have genetic testing done. * Some participants will be contacted for more testing.

A Study of LY4257496 in Participants With Cancer (OMNIRAY)

The main purpose of this study is to evaluate safety, tolerability, and efficacy of LY4257496 alone and as part of relevant standard of care (SOC) combination therapy in participants with Gastrin-releasing Peptide Receptor (GRPR)-positive advanced cancer, including but not limited to breast, colorectal, prostate, endometrial, esophageal, gastroesophageal (GE) junction, and gastric cancer. The study will also evaluate the safety, tolerability, and efficacy of LY4257529 to identify cancer with high levels of a protein called GRPR. This is a 2-part study. Participation could last up to 36 weeks or until your tumor progresses.

Malignant Gastric Outlet Obstruction Study With Stomach Partitioning (GO-PART)

The goal of this clinical trial is to evaluate whether stomach-partitioning gastrojejunostomy (SPGJ) more effectively reduces postoperative delayed gastric emptying (DGE) compared to conventional gastrojejunostomy (CGJ) in patients with unresectable stage IV gastric cancer accompanied by malignant gastric outlet obstruction (MGOO). This multicenter randomized trial aims to establish a new surgical standard that enhances recovery and quality of life in advanced gastric cancer. The main questions are: 1. Does SPGJ significantly decrease DGE compared with CGJ? 2. Does SPGJ enable faster food tolerance, shorter hospital stay, and earlier chemotherapy? Researchers will compare two arms - SPGJ and CGJ - to determine differences in postoperative gastric emptying, hospital course, complications, and survival outcomes. Participants Eligible participants are adults aged 20-85 years with histologically proven unresectable gastric adenocarcinoma limited to the lower third of the stomach and endoscopic or radiologic evidence of obstruction. Patients with total bowel obstruction, middle-third tumor extension, emergency conditions, or severe malnutrition (albumin \< 2.5 g/L) are excluded. Interventions * CGJ arm: Standard laparoscopic gastrojejunostomy using a 60 mm stapler without partitioning. * SPGJ arm: Laparoscopic transverse gastric partitioning 5 cm proximal to the tumor with a 2 cm bridge at the lesser curvature, followed by stapled gastrojejunostomy. All operations follow standardized training videos and pretrial workshops to ensure consistency across 32 Korean university hospitals. Study Design This is a prospective, randomized controlled multicenter trial (KLASS 16). After intraoperative diagnostic laparoscopy confirms eligibility, participants are randomized by a secure web-based block system stratified by hospital. A total of 144 patients (72 per arm) will be enrolled, ensuring 90% statistical power based on expected DGE rates (CGJ 34.6% vs SPGJ 3.8%). Endpoints * Primary endpoint: Incidence of DGE within 30 days (ISGPS criteria). * Secondary endpoints: Day of oral tolerance (GOO score ≥ 2), hospital stay, Clavien-Dindo ≥ II complications, mechanical obstruction recurrence, 6 and 12 month overall survival, and quality of life. Data Collection and Analysis Data will include postoperative nutrition recovery, complication grades, and survival follow-up. Analyses will utilize Chi square or Fisher's exact test for DGE rates and Kaplan-Meier with log rank testing for survival. Logistic regression will identify DGE risk factors. Duration Total 3 years: 6 months preparation, 1 year enrollment, 1 year follow up, and 6 months for data analysis and reporting. Expected Outcomes SPGJ is expected to reduce DGE by \> 70%, shorten hospital stay by \~3 days, and enable earlier chemotherapy, thereby improving palliative care outcomes and overall patient quality of life. The KLASS 16 trial will provide the first multicenter, Level I evidence to determine whether SPGJ should replace CGJ as the standard palliative procedure for MGOO.

A Study of LY4337713 in Participants With FAP-Positive Solid Tumors

This is a study of LY4337713 in participants with certain types of cancer that is advanced or has spread. Participants must have cancer with high levels of a protein called fibroblast activation protein (FAP). The purpose of this study is to evaluate safety, side effects, and efficacy of LY4337713. In addition, this study will evaluate how much LY4337713 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. For each participant, the study will last about 5 years.

Methylation Profile Test (Methylscape) in Body Fluids for Multi-Cancer Detection and Monitoring in Colombia

DNA methylation changes occur early and broadly during carcinogenesis. Methylscape is a rapid assay that detects global DNA methylation patterns in body fluids (blood, urine, and saliva) and may detect a cancer signal and predict the cancer signal origin (CSO) from a single fluid sample, using the differential interaction between methylated and unmethylated DNA and gold nanoparticles. This prospective observational study evaluates the diagnostic performance (sensitivity and specificity) of the Methylscape test in Colombian patients with various biopsy-confirmed solid tumors compared with age- and sex-matched cancer-free (healthy) volunteers. The study is conducted in three parts: Phase 1 validates the assay in 250 patients with cancer; Sub-study 2a compares 1,500 patients with cancer against 1,500 matched cancer-free volunteers; and Sub-study 2b uses serial blood and urine sampling in 300 patients with early-stage disease to assess detection of disease relapse during follow-up, in parallel with standard imaging. The study also estimates positive and negative predictive values (PPV/NPV) and projects the budget impact and cost-effectiveness of Methylscape as a multi-cancer early detection (MCED) tool in an upper-middle-income Latin American setting.

A Study of Disitamab Vedotin With Other Anticancer Drugs in Solid Tumors

This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer. Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2. This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®. This study will test how safe and how well DV with tucatinib works for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.

A Study of SGN-CEACAM5C in Adults With Advanced Solid Tumors

This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat. Participants in this study must have cancer that has come back or did not get better with treatment. Participants must have a solid tumor cancer that can't be treated with standard of care drugs. This clinical trial uses an experimental drug called PF-08046050. PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells. This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body. This study has 5 different study parts. Part A and Part B of the study will find out how much PF-08046050 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046050 is safe and if it works to treat certain solid tumor cancers. Part D and E of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given in combination with other anti-cancer agents. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with other anti-cancer agents and if it works to treat a certain solid tumor.

TEAS Timing for Gastrectomy Recovery (TEAS-TIME Trial)

The goal of this clinical trial is to learn if transcutaneous electrical acupoint stimulation (TEAS) works to help people recover faster after laparoscopic surgery for stomach cancer. TEAS is a treatment that uses small electrical pulses through sticky pads on the skin. It does not use needles. The main questions it aims to answer are: Does TEAS help people pass gas (a sign that the digestive system is waking up) sooner after surgery? Does TEAS help lower pain after surgery? Does TEAS reduce the need for extra pain medication after surgery? Researchers will compare three groups to see if TEAS works better when given before, during, and after surgery compared with only after surgery. Group 1 receives TEAS before, during, and after surgery. Group 2 receives a sham (inactive) treatment before and during surgery, and real TEAS after surgery. Group 3 receives sham treatment at all time points. All participants will receive the same standard pain relief and recovery care after surgery. Participants will: Be randomly assigned (like flipping a coin) to one of the three groups Receive TEAS or sham treatment for 30 minutes before surgery, during surgery, and for 30 minutes each day on the first 3 days after surgery Rate their pain on a 0-10 scale at 6, 12, 24, 48, and 72 hours after surgery Complete quality-of-life questionnaires before surgery, on day 4 after surgery, and 30 days after surgery Have a follow-up visit or phone call 30 days after leaving the hospital This study includes 300 adults aged 18 to 80 years who are scheduled to have laparoscopic surgery for stomach cancer at 13 hospitals in Shandong Province, China.

A Phase IV Randomized Trial of Maxigesic® Versus Standard Analgesia After Radical Gastrectomy

Background: Radical gastrectomy causes moderate-to-severe pain during the first 48 hours after surgery. Opioids are effective but carry adverse effects and risks of prolonged use, so ERAS-based care recommends multimodal analgesia. Acetaminophen is the most commonly used non-opioid analgesic in gastrectomy patients; adding ibuprofen as a fixed-dose combination has shown improved analgesia and opioid-sparing effects compared with acetaminophen alone in other surgical populations, but direct evidence in gastrectomy patients is limited. Objective: To evaluate whether scheduled administration of an acetaminophen-ibuprofen fixed-dose combination (Maxigesic® IV) is superior to acetaminophen alone for pain relief after radical gastrectomy, with exploratory assessment of cost-effectiveness and of differences in analgesic efficacy according to genetic polymorphisms. Hypothesis: When given on an identical scheduled regimen, the acetaminophen-ibuprofen fixed-dose combination produces significantly lower pain scores (NRS) over the first 48 postoperative hours than acetaminophen alone (superiority). Study plan: This is a phase IV, multicenter, double-blind, randomized controlled trial in which 160 gastric cancer patients scheduled for minimally invasive radical gastrectomy (80 per arm) are randomized 1:1 with stratification by institution. In both arms, the assigned drug is given as a 15-minute intravenous infusion every 6 hours, starting 30 minutes before the end of surgery through 48 hours postoperatively. The primary endpoint is the between-group difference in the time-weighted average (TWA) of repeatedly measured resting and active NRS over 48 hours, analyzed using a mixed model for repeated measures (MMRM); secondary endpoints include opioid consumption (MME), the Quality of Recovery score (QoR-15K), the incidence of chronic postsurgical pain (CPSP), and in-hospital costs.

A Study of Sigvotatug Vedotin in Advanced Solid Tumors

This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study sigvotatug vedotin to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether sigvotatug vedotin works to treat solid tumors. The study will have four parts. * Part A of the study will find out how much sigvotatug vedotin should be given to participants. * Part B will use the dose found in Part A to find out how safe sigvotatug vedotin is and if it works to treat solid tumors. * Part C of the study will find out how safe sigvotatug vedotin is in combination with these other drugs. * Part D will include people who have not received treatment. This part of the study will find out how safe sigvotatug vedotin is in combination with these other drugs and if these combinations work to treat solid tumors. * In Parts C and D, participants will receive sigvotatug vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin.

Default Option Nudging Intervention to Improve the Adherence Rates of Cancer Screening

The goal of this clinical trial is to learn if a behavioral "nudge" strategy, specifically a default option, can improve screening participation in populations at high risk for lung and stomach cancer. The main questions it aims to answer are: 1. Does presenting a screening appointment as a default option increase the likelihood that high-risk individuals will choose to be screened? 2. How do participants react, and what is their level of acceptance, when the nudge intervention is disclosed to them? 3. Does this transparency (disclosing the nudge) change their subsequent screening decisions? Researchers will compare a default option group to a standard control group to see if the nudge effectively increases screening adherence. Participants will: 1. Read a short educational text about lung or stomach cancer and its screening. 2. Complete an online questionnaire. 3. Make a decision regarding a simulated cancer screening appointment. 4. Read a disclosure explaining the behavioral nudge strategy used during the study. 5. Re-evaluate their screening decision and answer questions regarding their attitude toward the nudge.

Perioperative Therapies in Locally Advanced Unresectable Gastric Cancer

Gastric cancer (GC) is the fifth most commonly diagnosed cancer, with over one million cases diagnosed annually worldwide. Human epidermal growth factor receptor 2 (HER2) overexpression in GC (seen in 4.4% to 53.4% of patients in different reports) is predictive biomarker of response to HER2-targeting therapies. Trastuzumab in combination with cisplatin or oxaliplatin, and a fluoropyrimidine (capecitabine or 5-fluorouracil \[5-FU\]), is approved anti-HER2 therapy for first-line treatment of HER2-positive gastric or gastroesophageal junction (GEJ) cancer. Rilvegostomig 750 mg Q3W was selected as recommended Phase 2 dose based on all available ARTEMIDE-01 clinical safety, efficacy, PK, RO data as well as modeling analysis. The dose of 750 mg Q3W is predicted to achieve intra-tumoral RO of ≥ 90% in the majority of participants across a broad spectrum of conditions. This is a phase II study to initially assess the efficacy of perioperative Trastuzumab Deruxtecan (T-DXd) and Capecitabine combination with or without Rilvegostomig in patients with HER2 positive locally advanced unresectable GC and potentially by subsequent protocol amendment in HER2 low locally advanced GC. Other agents may also subsequently be assessed in this protocol, by protocol amendments . \---------------------------------------------------------------------------------------------------- Therefore, these studies provide robust evidence that immune checkpoint inhibitors plus chemotherapy, specifically the perioperative durvalumab plus FLOT regimen, can increase pCR rate and significantly improve long-term survival outcomes for patients with resectable gastric, GEJ, or esophageal cancer.

One-Click Autofocus Versus Segmented Focus in Gastric Endoscopy

Magnifying endoscopy provides high-resolution images that enhance the detection of early gastrointestinal lesions. However, conventional manual zoom techniques require frequent focal adjustments, which can be technically demanding and may compromise image stability, especially in complex anatomical settings. This study evaluates a novel one-click autofocus system based on image recognition and computer vision algorithms. The system automatically adjusts focal distance within seconds, eliminating the need for manual operation. This trial aims to compare the efficiency and image quality of one-click autofocus versus segmented manual focus in patients undergoing magnifying endoscopy for gastric diseases. A tandem randomized controlled trial will be conducted to assess procedure time, image clarity score, and operator satisfaction between the two techniques.

A Study of the Effectiveness and Safety of Nivolumab Plus Chemotherapy in Participants With Untreated Advanced/Recurrent Gastric Cancer

The purpose of this study is to assess the effectiveness, safety, and actual treatment status of first-line nivolumab plus chemotherapy in participants with untreated advanced / recurrent gastric cancer in a Japanese real-world setting.

To Evaluate IAH0968 in Combination With CAPEOX in HER2-positive Gastric Cancer

The safety, tolerability, and determination of the maximum tolerated dose (MTD) of the combination therapy were first evaluated for IAH0968 in combination with or without the CAPEOX regimen in unsystematically treated subjects with HER2-expressing advanced/metastatic colorectal or gastric cancers (including adenocarcinomas of the gastro-esophageal junction) or HER2-hypo-expressing advanced/metastatic solid tumors. The efficacy of IAH0968 in combination with the CAPEOX regimen versus trastuzumab in combination with the CAPEOX regimen in subjects with HER2-positive advanced/metastatic gastric cancer, including gastro-esophageal junction adenocarcinoma, was then assessed by progression-free survival (PFS) and OS according to the Research and Evaluation Criteria for the Evaluation of Efficacy in Solid Tumors (RECIST) 1.1.

PULSAR Combined With Immunotherapy for Unresectable Locally Advanced Gastric Cancer

The purpose of this prospective, single-center, phase II study is to evaluate the clinical efficacy and safety of combining first-line systemic therapy plus immunotherapy with personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR) in patients with unresectable locally advanced gastric cancer.

Single-port Versus Conventional Laparoscopic Surgery for Radical Proximal Gastric Cancer: A Randomized Controlled Trial

To evaluate the safety and efficacy of SP1000 and conventional laparoscopy in radical gastrectomy for proximal gastric cancer.

Conversion Therapy Plus Surgery and Radiotherapy for Retroperitoneal Nodal Metastases in Gastric Cancer

This is a randomized, controlled, multicenter phase II clinical trial evaluating the efficacy and safety of conversion therapy combined with radical gastrectomy and adjuvant radiotherapy targeting para-aortic (station 16) lymph nodes in patients with gastric adenocarcinoma and isolated station 16 nodal metastases. Eligible participants must have no evidence of peritoneal dissemination, visceral metastases, or non-regional lymphatic spread. Based on PD-L1 combined positive score (CPS), patients in the experimental arm will receive systemic therapy with SOX (S-1 plus oxaliplatin) with or without a PD-1 inhibitor, followed by D2 gastrectomy and postoperative adjuvant SOX chemotherapy, then intensity-modulated radiotherapy (IMRT) to the para-aortic region. The control arm will receive standard chemotherapy with CAPEOX or SOX, with or without immunotherapy, according to CPS status. The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. This study aims to explore whether the addition of locoregional treatment to systemic therapy improves long-term outcomes in this select patient population.

Efficacy and Safety of Serplulimab Combined With Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer or Adenocarcinoma of Esophagogastric Junction

This is a multicenter, double-blind, randomized, phase 2 trial to investigate the efficacy and safety of serlulimab combined with nab-paclitaxel plus SOX versus nab-paclitaxel plus SOX alone as neoadjuvant treatment for locally advanced GC or AEG. The goal of this clinical trial is to learn if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. It will also learn about the safety of serlulimab combined with nab-paclitaxel plus SOX. The main questions it aims to answer are: Does serlulimab increase the pCR of participants with locally advanced AEG/GC ? What medical problems do participants have when taking serlulimab? Researchers will compare to a placebo (a look-alike substance that contains no drug) to see if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. Participants will: Eligible patients were randomly assigned to receive serlulimab (4.5 mg intravenously on day 1) combined with chemotherapy (nap-paclitaxel 260 mg/m2 intravenously on days 1, OXA 130mg/ /m2, intravenously on days 1, and S-1 40 to 60 mg orally twice daily depending on BSA on days 1 to 14) or chemotherapy alone every 3 weeks for 3 preoperative cycles followed by 3 postoperative cycles. All patients will be followed for survival.

Spanish Validation of KOQUSS-40 Questionnaire: Assessing QoL of Gastric Cancer Patients After Gastrectomy: SPQUSS-41

The main objective of this study is the translation, linguistic adaptation into Spanish, and validation of the Korean quality of life questionnaire KOQUSS-40. This tool will allow us to objectively measure the quality of life of patients in clinical trials.

Prevalence of Helicobacter Pylori Infection and Gastric Cancer in the West Indies

Estimating the prevalence of Helicobacter Pylori infection in newly diagnosed stomach cancers in the West-Indies will help to understand the epidemiology of this cancer, which is over-incident in the West Indies compared to France. In addition, the constitution of a biobank (tumor tissues, healthy tissues and serum) will allow to set up in a second time etiological studies to identify other risk factors in particular in connection with the exposure to environmental pollutants to adapt the prevention measures.

Proximal Versus Total Gastrectomy for Locally Advanced Siewert Type II-III Gastroesophageal Junction Cancer

This multicenter prospective randomized clinical trial aims to compare the safety and oncological effectiveness of proximal gastrectomy and total gastrectomy in patients with locally advanced Siewert type II-III gastroesophageal junction cancer. Eligible patients will be randomly assigned to undergo either proximal gastrectomy or total gastrectomy using open, laparoscopic, or robotic surgical approaches according to clinical suitability. The primary outcome of the study is 3-year disease-free survival. Secondary outcomes include postoperative mortality, postoperative complications, and the number of metastatic lymph nodes retrieved. Patients will be followed for up to five years after surgery to evaluate long-term oncological outcomes.