Clinical Research Directory

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.

Acquisition of Blood and Tumor Tissue Samples From Patients With Gastrointestinal Cancer

Background: \- Gastrointestinal cancers can occur in the throat, stomach, gallbladder, liver, pancreas, and colon. Researchers are interested in evaluating how active the immune system is in trying to fight the cancer by studying blood and tumor tissue donated from individuals who have been diagnosed with gastrointestinal cancers. Objectives: \- To collect blood and tumor samples from individuals who have been diagnosed with gastrointestinal cancers in order to study the immune system s response to the cancer. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with throat, stomach, gallbladder, liver, pancreatic, or colon cancer, and are scheduled to be treated at the National Institutes of Health. Design: * The study will require at least one but no more than four visits to the National Institutes of Health Clinical Center. * Participants will be screened with a physical examination and medical history, and will provide a baseline blood sample for study. * Participants will provide additional blood samples 2 and 4 months after the baseline sample, as well as a final sample at the completion of the treatment protocol. * Participants will provide tumor tissue samples only if they undergo a surgical procedure related to the treatment for their gastrointestinal cancer. * No treatment will be provided as part of this protocol.

Prospective Procurement of Tumor Tissue to Identify Novel Therapeutic Targets and Study the Tumor Microenvironment

Background: Many advances have been made in cancer treatments, but more research is needed. Comparing samples of cancerous tissue to samples of normal, noncancerous tissues may help find differences between them. These differences may help researchers find new ways to treat cancer. Objective: To collect tissues and blood samples from people with known or suspected cancer. The samples will be used to help identify new targets for cancer treatments. Eligibility: People aged 18 years and older with a known or suspected cancer that requires surgery or biopsy. Design: Participants will be screened. They will answer questions about their health. They can do this on the phone or in person. Researchers will collect information from participants medical records. Data may include information about any prior or current cancers. Data about other medical conditions may also be collected. Participants will have blood drawn. Some of the blood will be tested for HIV and hepatitis B and C. Some of the blood will be used for genetic research. Participants will have tissue samples collected during surgeries or biopsies. These are procedures the participants would have had as part of their standard care. No new procedures will be done just for this study. Researchers may also seek out samples from prior procedures the participant had done. Participants will remain in the study for 6 months. They may have blood drawn again. Researchers may also collect tissue samples from any procedures performed during that time.

Effect of Silkworm Pupa Tablets in Gastrointestinal Malignancies at Nutritional Risk Following Radical Surgery

This is a randomized, double-blind, very low dose parallel-controlled, prospective, multi-center trial evaluating the improvement of nutritional status and frailty with silkworm pupa tablets after radical resection of gastrointestinal malignancies for 3 months intervention. The primary endpoints are body weight and frailty prevalence, The secondary endpoints are body mass index (BMI), skeletal muscle index (SMI) at the third lumbar vertebra (L3-SMI), sarcopenia prevalence and quality of life.

Sarcopenia Risk Screening in Patients With Gastrointestinal Cancer Using SARC-F

Sarcopenia is a syndrome characterized by progressive loss of skeletal muscle mass and strength and is associated with worse outcomes in cancer patients. It can negatively affect prognosis, increase postoperative complications, reduce tolerance to systemic therapy, and impair quality of life. Sarcopenia may be present even in patients with preserved nutritional status or overweight. This study evaluated the proportion of patients with gastrointestinal cancer who were at risk of sarcopenia, as assessed by the SARC-F screening questionnaire, before initiation of systemic treatment and during treatment. Patients with a positive screening result could be referred for further nutritional evaluation and assessment of sarcopenia severity using anthropometric measurements and DXA, according to standard clinical practice.

A Study of DB-1324 in Advanced/Metastatic Gastrointestinal Tumors

This study, the first clinical trial, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of DB-1324.

EQUITY GI: A Prospective Study to Enhance Quality, Inclusivity, and Trial Participation in Black Patients With Gastrointestinal Cancer.

This research study is being conducted to improve the quality of care of participants who have a diagnosis of gastrointestinal cancer (anal, colon, rectal, esophageal, stomach, small bowel, appendix, pancreas, gall bladder, liver, neuroendocrine tumor of gastrointestinal origin). This study has 3 components as follows- 1. Ensuring appropriate biomarker testing and evidence-based care: Biomarkers are molecules in the tumor or blood that indicate normal or abnormal processes in participant's body and may indicate an underlying condition or disease. Various molecules, such as DNA (genes), proteins, or hormones, can serve as biomarkers since they all indicate something about participant's health. Biomarker testing can also help choose participant's treatment. Additionally, a tumor board will be conducted periodically to provide treatment recommendations to participant's treating physician. Participants will receive standard-of-care treatment if participant enroll in this study. Participant will not receive any experimental treatment. 2. Assistance with clinical trial enrollment. The study team will help participants enroll in a clinical trial appropriate for participant's condition. However, enrolling in a clinical trial is totally up to the participant. 3. Health literacy: The study team will provide information relevant to participant's diagnosis to enrich participant's understanding of participant's condition and treatment. Investigator will provide questionnaires to assess participant's understanding before and after participant's have been provided with educational/informational material appropriate for participant's diagnosis.

EAT-ING: Enhancing Anticancer Treatment Safety Via Immunomodulatory Nutritional Support in Advanced Gastrointestinal Cancers

The use of immunomodulants in patients with GI cancer has been progressively gaining attention in the last years, as a high-calorie-high-protein nutritional blend enriched in immunonutrients has shown efficacy in several studies in reducing the risk of post-operative complications and the length of stay of patients undergoing major cancer surgery. The guidelines for the nutritional management of patients with cancer agree on the utility of nutritional support, whenever it is necessary, to improve clinical outcomes, and the efficacy and tolerability of treatments. To our knowledge, this is among the first clinical trial specifically designed to evaluate the role of immunomodulants-enriched ONS in combination with nutritional counseling in reducing serious AEs rate in patients with advanced GI cancers undergoing systemic treatments.

A Study of Selective Internal Radiation Therapy for the Management of Chemotherapy-induced Thrombocytopenia With Splenomegaly in Adult Subjects With Gastrointestinal Cancer

This is a prospective, interventional, open-label, single-arm, multicenter pilot study evaluating the safety, tolerability and maximum tolerated dose (MTD) of splenic Selective Internal Radiation Therapy (SIRT) using TheraSphere in adult patietns with gastrointestinal cancer and chemotherapy-induced thrombocytopenia with splenomegaly

Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer

Background: Many cancer cells produce substances called antigens that are unique to each cancer. These antigens stimulate the body s immune responses. One approach to treating these cancers is to take disease-fighting white blood cells from a person, change those cells so they will target the specific proteins (called antigens) from the cancer cells, and return them to that person s blood. The use of the white blood cells in this manner is one form of gene therapy. A vaccine may help these modified white cells work better. Objective: To test a cancer treatment that uses a person s own modified white blood cells along with a vaccine that targets a specific protein. Eligibility: Adults aged 18 to 72 years with certain solid tumors that have spread after treatment. Design: Participants will undergo leukapheresis: Blood is removed from the body through a tube attached to a needle inserted into a vein. The blood passes through a machine that separates out the white blood cells. The remaining blood is returned to the body through a second needle. Participants will stay in the hospital for 3 or 4 weeks. They will take chemotherapy drugs for 1 week to prepare for the treatment. Then their modified white cells will be infused through a needle in the arm. They will take other drugs to prevent infections after the infusion. The vaccine is injected into a muscle; participants will receive their first dose of the vaccine on the same day as their cell infusion. Participants will have follow-up visits 4, 8, and 12 weeks after the cell infusions. They will receive 2 or 3 additional doses of the boost vaccine during these visits. Follow-up will continue for 5 years, but participants will need to stay in touch with the gene therapy team for 15 years. ...

A Study to Test Different Doses of BI 765049 Alone and in Combination With Ezabenlimab in Asian People With Advanced Cancer (Solid Tumours) Positive for B7-H6

This is a study in adults from Asia with different types of advanced cancer (solid tumours). People can join the study if they have cancer of the stomach, large bowel and rectum, pancreas, liver, head and neck or non-small cell lung cancer. This is a study for people for whom previous treatment was not successful or no treatment exists. People can participate if their tumour has the B7-H6 marker. The purpose of this study is to find the highest dose of BI 765049 that people with advanced cancer can tolerate when taken (alone and) together with ezabenlimab. Another purpose is to check whether BI 765049 taken (alone and) together with ezabenlimab can make tumours shrink. Both medicines may help the immune system fight cancer. Participants can stay in the study up to 3 years, as long as they can tolerate it and can benefit from it. During this time, they visit the study site about every 3 weeks. At the study site they get BI 765049 alone or in combination with ezabenlimab as an infusion into a vein. BI 765049 is given in 3-week cycles, ezabenlimab is given once every 3 weeks. The doctors check the health of the participants and note any health problems that could have been caused by BI 765049 or ezabenlimab. Doctors regularly check the size of the tumour and check whether it has spread to other parts of the body.

The PhOCus Trial: Implementation of Pharmacogenomic Testing in Oncology Care

Doctors leading this study hope to find out if giving study participants' genetic information to cancer care providers will help personalize chemotherapy dosing decisions and decrease common chemotherapy side effects. Doctors leading the study will collect genetic information from study participants using pharmacogenomics/genotyping. Pharmacogenomics is the study of how the differences in our genes can affect our unique response to medications. This is a randomized study, which means that participants in this study will be randomly assigned (as if "by flip of a coin") to one of two different groups: a "pharmacogenomics group" or "control group".

Palliadelic Treatment to Reduce Psychological Distress in Persons With Advanced Gastrointestinal Cancers

The primary objective of this study is to evaluate the ability to recruit and retain participants, and to successfully conduct a psilocybin-based protocol, for a study of the treatment of distress related to stage IV or inoperable gastrointestinal cancers. Secondary objectives include pre/post, and longitudinal measurement of distress in intervention participants and a paired family member who is in an observational arm.

Harvesting Cells for Experimental Cancer Treatments

Background: The NCI Surgery Branch has developed experimental therapies that involve taking white blood cells from patients' tumor or from their blood, growing them in the laboratory in large numbers, and then giving the cells back to the patient. Objective: This study will collect white blood cells from normal volunteers and white blood cells and/or tumor cells, from patients who have been screened for and are eligible for a NCI Surgery Branch treatment protocol. The cells collected from normal volunteers will be used as growth factors for the cells during the period of laboratory growth. The cells and/or tumor from patients will be used to make the cell treatment product. Eligibility: Patients must be eligible for a NCI Surgery Branch Treatment Protocol Normal Volunteers must meet the criteria for blood donation Design Both patients and normal Volunteers will undergo apheresis. Patients will then undergo further testing as required by the treatment protocol. There is no required follow up for normal volunteers.

Extracellular Vesicles and Chemotherapy-Induced Peripheral Neuropathy

The goal of this clinical trial is to learn whether extracellular vesicles (EVs) in the blood can be used as biomarkers to predict chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer patients receiving chemotherapy with taxanes, platinum compounds, or antimitotic drugs. The main questions the study aims to answer are whether blood levels of EVs change in patients who develop CIPN during and after chemotherapy and whether specific features of EVs, including lipids and microRNAs, are associated with the development and severity of CIPN. Participants will be followed from before the start of chemotherapy until six months after treatment ends to evaluate how changes in EVs relate to nerve damage caused by chemotherapy. During the study, participants will provide blood samples before chemotherapy, at the end of treatment, and six months later for measurement and molecular analysis of EVs, will complete questionnaires about neuropathy symptoms, and will undergo simple, non-invasive nerve function tests using a tuning fork (diapason) and a Neuropen device. This study does not test cancer drugs; instead, it aims to identify biological markers in blood that may help predict which patients are at higher risk of developing CIPN, with the goal of improving monitoring and care during cancer treatment.

Sarcopenia and Neuromuscular Block in Gastrointestinal Cancer Surgery

This prospective observational study aims to evaluate the effects of sarcopenia on intraoperative neuromuscular block (NMB) in patients undergoing gastrointestinal cancer surgery. Adult patients scheduled for elective gastrointestinal cancer surgery will be grouped as sarcopenic or non-sarcopenic based on preoperative abdominal CT scans. Neuromuscular block parameters, including onset time, depth, duration, and recovery, will be objectively measured using TOF (Train-of-Four) monitoring. The study seeks to determine whether sarcopenia influences sensitivity to muscle relaxants and to contribute to individualized anesthesia management and patient safety.

Frailty in Patients With Gastrointestinal Cancer Who Are Undergoing Major Surgery

This research is for patients who have gastrointestinal cancer and have a planned major surgery. The purpose of this research is to identify cancer patients who may be at risk for frailty. Frailty is common in older adults and may include symptoms of weight loss, weakness, fatigue, low activity, slow walking and other illnesses. Frailty may increase the risk of problems after major surgery. The study will involve a survey, a blood sample, and a review of medical records.

ctDNA-guided Surveillance for Stage III CRC, a Randomized Intervention Trial

IMPROVE-IT2 is a randomized multicenter trial comparing the outcomes of ctDNA guided post-operative surveillance and standard-of-care CT-scan surveillance. The hypothesis of this study is that ctDNA guided post-operative surveillance combining ctDNA and radiological assessments could result in earlier detection of recurrent disease and identify more patients eligible for curative treatment.

BOLSTER: Learning New Skills to Thrive

This research study is evaluating a new program called Building Out Lifelines for Safety, Trust, Empowerment, and Renewal or (BOLSTER), which was designed to support participants with a gynecological or gastrointestinal cancer and new and complex care needs.

A Study of Raludotatug Deruxtecan (R-DXd) in People With Gastrointestinal Cancers (MK-5909-005)

Researchers are looking for new ways to treat certain types of advanced gastrointestinal (GI) cancers. The study medicine raludotatug deruxtecan (also called MK-5909, R-DXd, or DS-6000a) is a type of medicine called an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goal of this study is to learn if the cancer responds to treatment (gets smaller or goes away).

Study of Patritumab Deruxtecan in Participants With Gastrointestinal Cancers (MK-1022-011) (HERTHENA-PanTumor02)

Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain gastrointestinal (GI) cancers. The GI cancers being studied are advanced (the cancer has spread to other parts of the body). The goals of this study are to learn: * About the safety and how well people tolerate of patritumab deruxtecan * How many people have the cancer respond (get smaller or go away) to treatment

A Study on the Effects of Exercise on Side Effects From Treatment for Gastrointestinal Cancers

The purpose of this study is to find the level of aerobic exercise (AT) that is practical, is safe, and has positive effects on the body that may reduce the side effects of therapy. The study will also look at the way the body responds to exercise and whether there are differences in treatment. This will include looking at the highest treatment dose participants receive, how many people stop, delay, or reduce the treatment, and whether additional medication is needed to treat side effects of therapy.

Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies

Background: Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is hyperthermic (heated) chemotherapy that washes the inside of the abdomen. CRS with HIPEC may help people with peritoneal carcinomatosis. These are tumors that have spread to the lining of the abdomen from other cancers. Researchers think they can improve the results of CRS with HIPEC treatment on these tumors by choosing the chemotherapy drugs used in HIPEC. Objective: To see if HIPEC after CRS can be improved, using either a model called the SMART (Sustained Microenvironment for Analysis of Resected Tissue) System or using 3-D cell culture (organoid) models, in order to test different chemotherapy drugs on tumors that were surgically removed prior to HIPEC treatment (these models are not attached to the body) versus tumors that were treated with HIPEC while still inside the body before being immediately surgically removed. Eligibility: Adults ages 18 and older who have peritoneal carcinomatosis that cannot be fully removed safely with surgery. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Electrocardiogram (EKG) Computed tomography (CT) scan Other imaging scans, as needed Tumor biopsy, if needed Laparoscopy (small cuts are made in the abdomen, and a tube with a light and a camera is used to see the organs in the abdomen), if needed Participants will enroll in NIH protocol #13C0176. This allows their tumor samples to be used in future research. Some screening tests may be repeated in the study. Participants will have CRS. As many of their visible tumors will be removed as possible during surgery except for a few specific tumors left to receive the HIPEC treatment. Then they will receive HIPEC and the remaining tumors will be immediately removed. Participants will be in the hospital for 7-21 days after this surgery (CRS with HIPEC). Participants will give tumor, fluid samples (from the abdomen during surgery), blood, saliva, cheek swab, and stool for research. They will complete surveys about their health and quality of life. Participants with peritoneal mesothelioma (mesothelioma primary only) will have genetic (DNA) testing to determine clinical (CLIA level) germline BAP1 status for research use. Participants will have follow-up visits for up to 5 years from CRS with HIPEC. If there is disease progression, participants may have CRS with HIPEC again. Participants will then have follow-up visits for up to 5 years from the date of last CRS with HIPEC.

Safety, PK and Efficacy of QXL138AM in Patients With Solid Tumors and Multiple Myeloma

Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with locally advanced un-resectable and/or metastatic solid tumors and multiple myeloma. The study is an open-label, multicenter, first in human study to be conducted in two major parts which are further organized into two sub-parts. Part A Dose Escalation is a modified 3+3 with the first two cohorts consisting of one subject each based on the low clinical starting dose. Dose escalation in solid tumors (Part A1) will be followed by dose finding in multiple myeloma (Part A2). Part B consists of dose expansion in solid tumors (Part B1) and multiple myeloma (Part B2) using the recommended dose for expansion from Part A