Clinical Research Directory

Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)

DESTINY-Gastric03 will investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or immunotherapy in HER2-expressing advanced/metastatic gastric/gastroesophageal junction (GEJ) and esophageal adenocarcinoma patients. Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or immunotherapy administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and preliminary anti-tumor efficacy so as to permit further clinical testing. T-DXd in combination with cytotoxic chemotherapy or immune checkpoint inhibitor administered to HER2-expressing gastric, GEJ and esophageal cancer patients who have not received prior treatment for advanced/metastatic disease will show preliminary evidence of anti-tumour activity and the potential to become a therapeutic option for this patient population.

Nutrition Intervention Trials in Linxian Follow-up Study

Two large, nutritional intervention trials were conducted in Linxian, China between 1985-1991. These trials tested the effect of multiple vitamins and minerals in the prevention of esophageal cancer in a population with the highest known rate for this disease in the world. Results from the trials showed that Beta-carotene + Vitamin E + selenium reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Multivitamins/minerals also showed reduction in premalignant lesions. Preliminary follow-up data obtained for the time period after cessation of intervention in 1991 suggests that the observed benefit for total and cancer mortality is reduced but that the benefit for stomach cancer remains. The objectives of the follow-up study are: (1) to continue to determine cancer incidence and all causes of mortality in trial participants after intervention to permit examination of potential effects of the interventions on total and cause-specific mortality and cancer incidence in the post-intervention period; (2) to conduct a cross-sectional nutritional survey in a subsample of living trial participants to evaluate their nutritional status, asses the validity of dietary questionnaires, and relate neurologic status to vitamin B12 plasma levels; (3) to collect a blood sample from all living trial participants to permit further etiologic investigations of genetic and environmental hypotheses; and (4) to perform nested case-control studies of selected genetic and environmental hypotheses. To accomplish the objectives of the follow-up study, we will: (1) determine updated vital status and cancer status data on all trial participants via monthly checks of village doctor records and quarterly checks of the Linxian Cancer Registry; conduct a Vital/Cancer Status Interview Survey among all (n-34,000 trial participants (or their surrogates); identify, collect, and store all available diagnostic materials for trial participants identified as having developed cancer or died with cancer during the follow-up period; (2) conduct a Nutritional Survey on a subsample (n-1000) of living trial participants that will include (a) a physical exam and brief medical history, (b) a neurologic history, (c) a cognitive function exam, (d) a hair/mouth skin exam, (e) a neurological exam, (f) a nutritional questionnaire, and (g) collection of a blood sample for hematologic/biochemical analyses; (3) conduct a Blood Collection Survey of all living trial participants (n-23,000) to obtain (a) a physical exam and brief medical history and (b) a single 10-ml blood sample for separation and preservation as WBCs (both viable and nonviable), RBCs, and plasma for genetic (e.g., xenobiotic polymorphisms) and environmental (e.g., plasma ascorbic acid) hypothesis testing; and (4) perform Nested Case-Control Studies of selected genetic and environmental hypothesis related to the etiology and prevention of esophageal cancer and stroke. These will be done using serum from the new cancer and stroke cases (-2500) and controls (-2500) previously identified from 1991-1996, as well as using new cancer and stroke cases and controls for the period 1996-2004 (-9000). The followup for endpoints will continue monthly for an additional 5 years (through the year 2003). The Nutritional Survey and Blood Collection Survey will be conducted in the spring of 1999. The Nested Case-Control studies will be performed annually beginning in 2000, and the Vital/Cancer Interview Survey will be conducted in the Spring of 2001.

The Effect of Different Digestive Tract Reconstruction Methods on Postoperative Quality of Life After Proximal Gastrectomy

Gastric cancer ranks as the fifth most common malignancy worldwide and the fourth leading cause of cancer-related deaths. In China, its incidence and mortality rank third among all cancers. While the global incidence of gastric cancer is declining, proximal gastric cancer and adenocarcinoma of the esophagogastric junction (AEG) are on the rise. Due to the unique characteristics of AEG, there is no standardized treatment consensus, making the selection of an optimal surgical approach and reconstruction method crucial for improving patient outcomes. For early-stage proximal gastric cancer and AEG, total gastrectomy (TG) and proximal gastrectomy (PG) are common surgical options. PG, increasingly favored for its function-preserving benefits, has been shown to be a safe and effective alternative to TG. While TG effectively removes lymph nodes and reduces reflux risk, it leads to permanent loss of gastric function and nutritional deficiencies. PG better preserves gastrointestinal function but is limited by the risk of reflux esophagitis, highlighting the need for improved reconstruction techniques. Several reconstruction methods exist after PG, including esophagogastric anastomosis, jejunal interposition, double-tract reconstruction (DTR), double-flap technique (DFT), and tubular gastric anastomosis, each with varying efficacy in preventing reflux. Studies suggest that DTR reduces reflux and improves quality of life compared to esophagogastric anastomosis, while DFT, first introduced in 1998, has gained popularity for its advantages in maintaining nutrition and minimizing reflux. Additionally, tubular gastric anastomosis, which constructs a narrow gastric tube to facilitate tension-free anastomosis, has shown potential benefits for AEG patients. Most existing studies on laparoscopic or robot-assisted reconstruction techniques for proximal gastric cancer are retrospective, lacking high-quality prospective evidence. Furthermore, comparative data on their anti-reflux efficacy and postoperative quality of life remains l

Response Prediction of Hyperthermic Intraperitoneal Chemotherapy in Gastro- Intestinal Cancer

Patients with gastric or colon cancer with peritoneal carcinomatosis will receive a biopsy of the tumor during their primary curative surgery. The operation is performed according to standard and includes resection of the primary tumor and any metastases and followed by HIPEC (Intraperitoneal hyperthermic chemoperfusion) according to the respective hospital standard. Organoid cultures from the biopsies are established in the research laboratory. Various chemotherapeutic agents are tested on these tumor organoids in the laboratory and the tumor organoids are analyzed in detail with regard to genetic alterations in order to find alterations that can be addressed, if necessary, by means of targeted drugs against peritoneal carcinomatosis.

A Study of STRO-004 in Adults With Refractory/Recurrent Metastatic Cancer

This is a study to evaluate the safety and preliminary anti-tumor activity of STRO-004 in adults with metastatic cancer. This study includes 3 parts: * Part 1A is a dose escalation study of STRO-004 monotherapy in selected tumor types known to commonly express Tissue Factor (TF). * Part 1B is a cohort expansion in 1 or more types of cancer to further evaluate a STRO-004 monotherapy dose, determine the best dose for use in later phases, and examine anti-tumor activity. * Part 1C is a dose escalation of STRO-004 combined with pembrolizumab to determine tolerability and preliminary anti-tumor activity of both drugs used together.

Radical Surgery Versus Non-Surgery in Gastric Cancer Patients With Peritoneal Metastasis After Successful Conversion Therapy

The goal of this clinical trial is to learn if radical surgery improves prognosis and quality of life compared with continued standard non-surgical treatment in gastric cancer patients with peritoneal metastasis who have achieved successful conversion therapy. The main questions it aims to answer are: * Does radical surgery prolong overall survival in patients who achieve successful conversion therapy? * Does radical surgery provide better or at least comparable quality of life and safety outcomes compared with continued standard treatment? Researchers will compare radical surgery versus continued standard systemic treatment to see whether radical surgery provides superior clinical benefit for patients after successful conversion therapy. Participants will: * Initial laparoscopic exploration confirms CY0P1 or CY1P1, absence of distant organ metastasis, a PCI ≤ 20, and presence or absence of ascites. * Receive conversion therapy (chemotherapy, targeted/immunotherapy, intraperitoneal therapy, etc.) per standard guidelines, tailored to the patient's condition and molecular-pathological profile * If clinical conversion is confirmed, undergo a second laparoscopic exploration to verify successful conversion * If successful conversion is confirmed (peritoneal lesions cleared or markedly regressed with negative biopsy, no ascites or distant metastases, R0-resectable primary tumor, and improved patient condition), be randomized 1:1 to either the surgery group or the standard treatment group * In the surgery group, undergo curative gastrectomy with D2 lymphadenectomy during the second laparoscopy, followed by adjuvant therapy and maintenance treatment * In the standard treatment group, continue systemic therapy without surgery, with maintenance treatment and salvage surgery permitted if clinically indicated * Complete quality of life questionnaires at predefined time points * Be followed up for survival, disease progression, adverse events and medical resource use outcomes

KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer

This is a phase I clinical trial to determine the maximum tolerated dose (MTD) of KK-LC-1 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1. Participants will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin. The safety profile and clinical response to treatment will be determined.

XELOX for 4 Months Versus 6 Months in Gastric Cancer (LOMAC)

Our study aims to compare 4 months versus 6 months of adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in patients with gastric cancer. Hypothesis: We hypothesize that a 4-month regimen of capecitabine plus oxaliplatin is noninferior to a 6-month regimen with respect to DFS and is associated with lower treatment-related toxicity.

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

Background: A new cancer therapy involves taking white blood cells from a person, growing them in the lab, genetically modifying them, then giving them back to the person. This therapy is called gene transfer using anti-KRAS G12V mTCR cells. Objective: To see if anti-KRAS G12 V mTCR cells are safe and can shrink tumors. Eligibility: Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface of tumors. Design: In another protocol, participants will: Be screened Have cells harvested and grown Have leukapheresis In this protocol, participants will have the procedures below. Participants will be admitted to the hospital. Over 5 days, participants will get 2 chemotherapy medicines as an infusion via catheter in the upper chest. A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter. For up to 3 days, participants will get a drug to make the cells active. A day after getting the cells, participants will get a drug to increase their white blood cell count. This will be a shot or injection under the skin. Participants will recover in the hospital for 1-2 weeks. They will have lab and blood tests. Participants will take an antibiotic for at least 6 months. Participants will have visits every few months for 2 years, and then as determined by their doctor. Visits will be 1-2 days. They will include lab tests, imaging studies, and physical exam. Some visits may include leukapheresis or blood drawn. Participants will have blood collected over several years.

AI-Assisted Novel rbcDNA Detection for Early Gastric Cancer Diagnosis

The goal of this clinical trial is to prospectively validate the diagnostic performance of an rbcDNA-based assay for gastric cancer detection in individuals undergoing upper gastrointestinal endoscopy. The study aims to evaluate the diagnostic accuracy of rbcDNA in distinguishing newly diagnosed, treatment-naïve gastric cancer from non-cancerous gastric conditions, using endoscopic and histopathological findings as the reference standard. The study will also compare the diagnostic performance of the rbcDNA-based approach with currently available clinical biomarkers, including serum tumor markers, Helicobacter pylori testing, and pepsinogen-related indices. All enrolled participants will provide a 2 mL peripheral blood sample for rbcDNA analysis.

Ovarian-Sparing Adaptive Radiotherapy in Young Adult Women

Female patients with early onset (\<50 years old) pelvic malignancies such as uterine and rectal cancers are rising in incidence, which often requires pelvic radiation; many of these patients are premenopausal and at a high risk of premature ovarian failure from radiotherapy. Premature ovarian failure carries significant cardiac, musculoskeletal, sexual, and psychosocial morbidity. Ovarian transposition carries variable success rates, is not readily accessible to the general population, and can still be at risk of clinically significant radiotherapy doses. There is an unmet need for innovative techniques to protect ovarian function.

A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors

This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma \[cutaneous/acral\], squamous cell carcinomas of the head and neck (SCCHN), HER2-negative gastric cancer ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer.

Using an End-of-life Conversation Game to Engage Patients With Cancer in Advance Care Planning: Phase 2

The goal of this clinical trial is to explore feasibility, acceptability, and effectiveness of end-of-life conversation game "Hello" as a tool to help individuals with various solid cancer types (including: breast, gastro-intestinal, lung, melanoma, head and neck, and/or genito-urinary cancers) treated at Penn State Health clinics and their loved ones perform advance care planning (ACP). The main questions it aims to answer are: What modifications and/or adaptations are necessary to Hello for use in cancer populations? What impact does participation in Hello event have on health care usage (e.g., number of hospitalizations, ICU admissions, emergency department visits, etc.)? How feasible is it to randomize participants to play either Hello for Cancer or Table Topics? Participants will: * Complete pre-game questionnaires * Play either Hello or Table Topics game * Complete post-game questionnaires * Participate in a focus group * Complete a telephone follow up interview 1-4 months after their event This study is a continuation of NCT06028152.

NOMAD-GI: Molecular-guided Non-operative Management and Organ Preservation Strategy After Precision Therapy in Gastrointestinal Cancers

The NOMAD-GI study is a single-center, bidirectional cohort study designed to evaluate the safety and efficacy of molecular biomarker-guided non-operative management (NOM) and organ preservation strategies after precision therapy in patients with gastrointestinal cancers. Patients with actionable molecular biomarkers, including dMMR/MSI-H, POLE mutation, PD-L1 high expression, tumor mutational burden-high (TMB-H), Epstein-Barr virus positivity (EBV+), HER2 positivity, CLDN18.2 positivity, and other actionable genomic alterations, will be enrolled. After immune checkpoint inhibitor or targeted therapy, patients achieving favorable clinical responses will undergo multidisciplinary team (MDT) evaluation and receive either non-operative management, local treatment, or radical surgery according to individualized treatment decisions. The study aims to establish a molecular-driven organ preservation paradigm for gastrointestinal cancers and evaluate whether NOM can provide comparable oncological outcomes while improving functional outcomes and quality of life.

CT Imaging and Clinical Features to Predict Outcomes in Patients With Gastric Cancer

The goal of this prospective observational study is to evaluate how well a previously developed prediction model can estimate outcomes in adults with gastric cancer. The model combines information from computed tomography (CT) images obtained before treatment with routine clinical information. The main questions are how well the model predicts how long participants live after treatment begins and whether their cancer progresses. Participants will receive their usual medical care. Researchers will collect pretreatment CT images, basic clinical and tumor information, laboratory and tumor marker results, treatment information, and follow-up outcomes obtained during routine care. These data will be entered into the predefined prediction model, and the model's predictions will be compared with what actually happens during follow-up. The study will not change the participants' usual treatment. Model predictions will be used for research purposes only and will not be used to make treatment decisions.

Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors

This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, pharmacokinetics (PK), and biomarker study of CBX-12 in subjects with advanced or metastatic refractory solid tumors.

Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.

IBI343 Combined With Sintilimab Plus Chemotherapy in Gastric Cancer

This is a Single-arm, Open-label, Phase 1b/2 Study of IBI343 Combined with Sintilimab Plus Chemotherapy in Previously Untreated, Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Safety and Efficacy Study of Sorbitol With Neoadjuvant Chemotherapy Combined With Tirellizumab (PD-1 Inhibitor) in Patients With Locally Advanced Gastric Cancer

The goal of this clinical trial is to learn if sorbitol works to enhance the therapeutic effect of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. It will also learn about the safety of sorbitol. The main questions it aims to answer are: Does sorbitol enhance the therapeutic effect of immunotherapy and increase the major response rate in patients with locally advanced gastric cancer? Does sorbitol with neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) can improve the prognosis of patients with locally advanced gastric cancer? Researchers will compare sorbitol to a standard-of-care treatment (aPD-1 + SOX chemotherapy) to see if sorbitol works to enhance the therapeutic effect (Add-on Effect) of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. Participants will: Take sorbitol every day for 3 months in 3 treatment cycles Visit the clinic once every 4 weeks for checkups and tests Keep a diary of their symptoms and the number of times they use a rescue inhaler Participants will follow up as planned until PD occurs, informed consent is withdrawn, or follow-up is lost (whichever occurs first). After the end of treatment and safety follow-up, all subjects will be followed up for survival (OS data collected every 3 months ±14 days).

Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis

Objective: To follow people with GISTs and collect tumor tissue so that it can be studied in the lab. Eligibility: People age 6 and older who have a GIST. Design: Participants will be screened with a review of their medical records and samples. Participants will enroll in 1 other NIH study, and may be asked to enroll in 2 other optional NIH studies. Participants will have a medical history and physical exam. Data about how they function in their daily activities will be obtained. Participants may speak with a genetic counselor. They may have genetic testing. Participants will give blood samples. They may have a cheek swab. For this, small brush will be rubbed against the inside of the cheek. Participants may have a computed tomography (CT) scan of the chest, abdomen, and pelvis. Or they may have a CT scan of the chest and magnetic resonance imaging (MRI) of the abdomen and pelvis. Participants will be monitored every 6-12 months at the NIH Clinical Center, for up to 10 years before having surgery. If they need surgery, it will be performed at the NIH. Then, they will be monitored every 6-12 months, for up to 5 years after surgery. If a participant has surgery, tumor tissue samples and research specimen will be taken. If a participant does not need surgery, their participation will end after 10 years. If they have surgery, the 5-year monitoring period will restart after each surgery.

Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours.

A Study of MRG007 (ARR-217) in Patients With Advanced Solid Tumors

This is an open-label, multi-center, phase I study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of MRG007 (ARR-217) in patients with unresectable locally advanced or metastatic solid tumors.

A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors

This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors

PD-1 Antibody Adjuvant Therapy for GC Patients With MSI-H After D2 Radical Surgery

Approximately 5% to 10% of gastric cancers have MSI-H/dMMR. According to the results of retrospective analysis of CLASSIC and MAGIC, MSI-H/dMMR was a good prognosis and potential negative predictor of adjuvant chemotherapy for resectable gastric cancer. GC patients with MSI-H/dMMR were relatively insensitive to chemotherapy. The prognosis of these patients receiving routine postoperative adjuvant chemotherapy was worse than that with surgery alone. However, these patients were sensitive to immunotherapy. MSI-H/dMMR is one of the most important biomarkers to predict the efficacy of immunotherapy for GC. In this study, patients with MSI-H locally advanced gastric adenocarcinoma after radical surgery with D2 dissection would be randomly treated with conventional adjuvant chemotherapy, PD-1 monoclonal antibody immunotherapy or follow-up observation. We intend to demonstrate that the prognosis of MSI-H GC patients after D2 radical gastrectomy receiving PD-1 monoclonal antibody immunotherapy would be better than that with standard postoperative adjuvant chemotherapy and follow-up observation.