Neoplasms

Background: Cancers that begin in the colon, adrenal glands, or bile ducts may spread to the liver. These liver tumors are often treated using a hepatic artery infusion (HAI) pump. The HAI pump is installed in the artery that goes to the liver; drugs are administered directly to the liver through this pump. But these tumors often return after treatment. Carfilzomib (CFZ) is a drug approved to treat another kind of cancer. Researchers want to find out if this drug may be helpful when administered through the HAI pump directly to the liver for people with colon, adrenal glands, or bile duct cancer that has spread to the liver. Objective: To test the safety of carfilzomib (CFZ) delivered via a hepatic artery infusion (HAI) pump directly to the liver in people with cancer in their liver. Eligibility: People aged 18 years or older with cancers of the colon, adrenal glands, or bile ducts that spread to the liver and persist after treatment. They must have a functioning hepatic artery infusion (HAI) pump in place from previous treatment of HAI pump therapy. Design: Participants will be screened. They will have a physical exam, blood tests, imaging scans, and a test of their heart function. They will also have a test to show how the blood flows through their liver: A radioactive substance will be injected into a vein, and a special camera will take pictures of the blood flow for up to 1 hour. Participants will receive the study drug for about 6 months. They will visit the clinic once a week. Their HAI pump will be filled with the drug at each visit; the drug will slowly drain from the pump into the liver. Blood tests and imaging scans will be repeated during the study. Participants will have follow-up visits 1 and 3 months after their last dose of study drug. An optional liver biopsy (tissue sample) for research purposes may be done before the study drug is given, and again (optional) within 28 days after first receiving the study drug. Individuals may participate in the study even if they do not agree to have the biopsies done. ...

Background: Prostate cancer is the second most common cause of cancer-related death among men in the United States. Early-stage, low-grade prostate cancer is managed with active monitoring. However, 35% of men with this cancer will need treatment within 5 years because of tumor growth. Researchers want to know if a new vaccine that targets 3 anti-cancer proteins (TriAdeno) plus a drug (N-803) approved for bladder cancer can help stop prostate tumors from growing. Objective: To test TriAdeno and N-803 in people with early-stage prostate cancer. Eligibility: People aged 18 years and older with early-stage low- or medium-risk prostate cancer. Design: Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have an imaging scan. They may have a rectal exam. TriAdeno is injected under the skin of the upper thigh; N-803 is injected under the skin of the abdomen. Participants will be treated in up to four 21-day cycles. They will get both injections on the first day of each cycle. Participants may opt to complete a memory aid: They may record all of their symptoms for 7 days after each injection. They may also complete a questionnaire about their prostate symptoms. Blood tests, imaging scans, and other tests will be repeated during the study. A tissue sample (biopsy) of the tumor will be collected during or after cycle 2; a second biopsy may be taken about 1 year later. Participants will have follow-up phone calls for 5 years....

The purpose of this study is to check how well LY35327021 works and how safe it is for controlling nausea and vomiting caused by chemotherapy. Participants who join this study will be in it until all parts are finished, which could take about 2 months.

This is a multi-site, global, open-label study that includes a phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with brain metastases from estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER-2) negative breast cancer. Phase 1b was designed to select the recommended phase 2 dose (RP2D) and is followed by an ongoing phase 2 evaluation of elacestrant in combination with abemaciclib in participants with active brain metastases from ER-positive, HER-2 negative breast cancer.

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....

Advanced cancer patients often experience significant physical and emotional symptoms, which can lead to frequent hospital visits and reduced quality of life. Although palliative care can help manage these symptoms and improve well-being, it is often introduced too late. A proactive symptom monitoring model, SPARKLE-2 aims to identify patients who need palliative care earlier by regularly checking their symptoms using a simple questionnaire. Patients with concerned symptoms will receive timely support from the palliative care team, with the goal of improving their quality of life, reducing unnecessary hospital admissions, and helping more patients receive care in the community rather than in hospital. In the earlier SPARKLE-1 study, it showed the improvement of patients' physical wellbeing. SPARKLE-2 seeks to test the effectiveness among advanced cancer patients with unplanned hospital visits while simultaneously collecting data on real-world implementation.

Background: \- Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome. Objectives: * To learn more about the types of cancers that occur in individuals with LFS. * To study the role of the TP53 gene in the development of cancer. * To look for other possible genes that cause LFS * To study the effect of LFS diagnosis on families. * To determine if environmental factors or other genes can change a person s cancer risk associated with LFS. Eligibility: * Individuals with a family or personal medical history of cancers consistent with LFS. * Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome) * Individuals with certain rare cancers * Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s). Design: * Participants will fill out a medical history questionnaire and a family history questionnaire. * Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams. * Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed. * Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.

Obstructive uropathy is a serious complication frequently seen in cancer patients, occurring when urine flow from the kidneys is blocked by tumor compression, invasion, or benign etiologies such as radiation-induced strictures and stones. If left untreated, this blockage leads to hydronephrosis, acute kidney impairment, and interruptions in cancer therapy. When internal ureteral stenting fails or is not possible, percutaneous nephrostomy (PCN), which involves inserting a small drainage tube through the back directly into the renal collecting system, is required to decompress the kidney and preserve renal function. Traditionally, PCN is performed under fluoroscopy, exposing patients and healthcare staff to ionizing radiation. Ultrasound guidance provides continuous real-time visualization of the renal structures while completely eliminating radiation hazards. The primary purpose of this prospective interventional study is to evaluate the technical success, safety, and complication rates of ultrasound-guided percutaneous nephrostomy in oncology patients presenting with urinary tract obstruction. Participants in this study undergo ultrasound-guided PCN under local anesthesia using the standard Seldinger technique to place an 8Fr pigtail drainage catheter. The study evaluates the technical success rate of the procedure, procedural and post-procedural complications (such as bleeding or sepsis), recovery of kidney function measured by changes in serum creatinine levels, and hospital length of stay.

The purpose of this trial is to evaluate a new drug, HTL0039732, that will be administered on its own (as a monotherapy) and in combination with atezolizumab or with other approved anti-cancer therapies, in participants with advanced solid tumours.

This study aims to evaluate the safety and tolerability of RO7673396 in participants with advanced solid tumors harboring RAS mutation(s). This study consists of two stages: Stage 1 (Dose Escalation) and Stage 2 (Dose Expansion). Stage 1 will define the recommended dose(s) for expansion (RDEs) of RO7673396. Stage 2 will evaluate preliminary anti-tumor activity of the RDE(s) defined in Stage 1 and of other doses of interest for future development in selected solid tumor indications.

Background: People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing. Objective: To learn if nilotinib and paclitaxel will benefit people with rare cancers. Eligibility: People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors. Participants will repeat the screening tests during the study. Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle. Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have. Participants may have optional tumor biopsies. Participants can stay on the study until their disease gets worse or they have intolerable side effects. Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

The purpose of this research study is to collect and analyze information from patients being treated with various forms of radiation therapy.

The purpose of Part 1 of this study is to determine a safe, tolerable, and feasible recommended total dose of intratumorally administered JNJ-1761981. The purpose of Part 2 of this study is to identify the optimal volumetric dose of JNJ-1761981 for the treatment of tumor lesions.

The purpose of this study is to determine the safety, feasibility, recommended dose(s) and regimen(s) of JNJ-87704916 as monotherapy and in combination with cetrelimab.

The purpose of this study is to determine safety and recommended phase 2 dose(s) (RP2Ds) of JNJ-87890387 and to determine the safety of JNJ-87890387 at the RP2D(s).

The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D\[s\]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.

This study tests whether an artificial intelligence (AI) system can help doctors write medical notes during cancer consultations. After a cancer patient is seen by a multidisciplinary team (a group of specialists who decide on the best treatment), they have a consultation with their oncologist to discuss the treatment plan. During this consultation, doctors must write detailed medical notes, which takes significant time and effort. In this study, an ambient AI system called VOCALI is used during oncology consultations at the National Cancer Center in Vilnius, Lithuania. Before the consultation begins, the doctor loads relevant pseudonymized clinical data from the electronic health record (such as diagnosis and treatment plan) into the system. During the consultation, VOCALI records the conversation (with the patient's consent) and combines it with the loaded clinical data to automatically generate a draft medical note in Lithuanian. Patients may ask the doctor to stop the recording at any time. The doctor then reviews the draft, makes any necessary corrections, and approves the final document. The AI does not make any medical decisions - the doctor is always responsible for the final note. What the study measures: The study has three main goals: * To assess the quality of the AI-generated notes, rated by two independent reviewers using the PDQI-10, a standardized documentation quality instrument translated into Lithuanian using forward-backward translation * To measure the time doctors spend reviewing and approving the AI-generated draft * To monitor safety - whether any AI errors could affect patient care The study also collects information on doctor workload, ease of use of the system, and patient satisfaction with the consultation. Who can participate: Adult patients (age 18 or older) attending a primary oncology consultation at the National Cancer Center in Vilnius, Lithuania, after a multidisciplinary team decision, who speak Lithuanian and provide written consent. Study details: 250 patients will be enrolled over 12 months. Each participant attends one consultation and completes a short satisfaction questionnaire (about 5 minutes). No additional visits are required. There is no comparator group - all participants receive the AI-assisted documentation. This is the first study to evaluate ambient AI documentation in the Lithuanian language and in the Lithuanian oncology setting.

The goal of this clinical trial is to test a new medicine called GSK5764227, which delivers a toxin directly to cancer cells to destroy them while sparing healthy cells. The study will combine GSK5764227 with standard treatments to evaluate its safety, examine how the body processes it, check if it triggers any immune responses, and assess whether it can shrink or control cancer.

The purpose of this study is to investigate a new drug GSK5533524 in adults with certain advanced cancers to find a safe dose and learn how well people tolerate it, so researchers can choose the best dose for the next stage of testing. The study will also check whether the drug can shrink tumours or slow cancer growth, monitor how the body absorbs and breaks down the drug, and look for any immune reactions that the body might develop against the treatment.

Background: Blood, tissue, and tumor cells contain genes. Genes are made up of DNA. DNA is the "instruction book" for each cell. In some people with cancer, the genes that might have slowed the growth of their tumor were "turned off." Researchers want to see if a new drug can turn the genes back on and slow the tumor growth. The drug is called Aza-TdC. Objective: To test the safety of Aza-TdC, and to find out the dose of this drug that can be safely given to humans. Eligibility: People ages 18 and older who have advanced cancer that has gotten worse after standard treatment, or for which no effective therapy exists Design: Participants will be screened with: Medical history Blood and urine tests Scans to measure their tumors Test to measure the electrical activity of the heart Participants will take the study drug by mouth. The drug is given in cycles. Each cycle is 21 days (3 weeks) long. Week 1 and week 2: participants will take the study drug once a day for 5 days. Then they will have 2 days without the drug. Week 3: no study drug is taken. This completes one cycle of treatment. For cycle 1, participants will repeat the screening tests several times. For all other cycles, participants will have blood tests and pregnancy tests. They will have scans of their tumor every 6 weeks. The cycle will be repeated as long as the participant tolerates the drug and the cancer is either stable or gets better. Sponsoring Institute: National Cancer Institute

This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all pediatric and adult participants exposed to Gene-modified (GM) T-cell therapy participating in a previous Celgene sponsored or Celgene alliance partner sponsored study. Participants who received at least one infusion of GM T cells will be asked to enroll in this LTFU protocol upon either premature discontinuation from, or completion of the prior parent treatment protocol.

Solid tumours are abnormal lumps of tissue that can occur in different parts of the body. The tumours involved in this study have specific genetic characteristics that can make them more aggressive and challenging to treat. The study will test whether GSK5460025 alone or in combination (potential combinations may be included in future amendments to the protocol) with other anti-cancer agents can decrease tumor size, is safe, well-tolerated, and how the drug is processed in the body over time.

Background: -Patients who are being evaluated and/or treated at the NIH Clinical Center and adult patients at participating sites will be entered onto this tissue procurement protocol for collection of tissue specimens. Objectives: * To obtain samples from adult and pediatric patients for research purposes from tests and procedures that are done as required by the primary research protocol(s) to which a patient is enrolled or as part of their standard-of-care treatment. * To obtain samples for research purposes from non-surgical procedures, such as percutaneous biopsies, performed for the sole purpose of obtaining tissue specimens or biological fluids for this protocol. Eligibility: -Adult patients (18 years of age and older) and pediatric patients (younger than 18 years of age) who are being evaluated for and/or treated for cancer at the NIH Clinical Center participating sites. Design: * This is a multicenter tissue procurement protocol with NCI as the coordinating center. * For adult patients: specimens for research purposes, as outlined in this protocol, will be obtained from tests and procedures that are done as required by the primary research protocols to which a patient is enrolled or as part of their standard-of-care treatment. Non-surgical procedures, such as percutaneous biopsies, may also be performed for the sole purpose of obtaining tissue specimens or biological fluids for this protocol. Tissues and biological fluids to be procured may include but are not limited to blood, serum, urine, tumor tissue, normal tissue, pleural fluid, CSF, saliva, bronchial alveolar lavage (BAL), circulating tumor cells, hair follicles, and bone marrow. These specimens will be stored with unique identifiers and used to perform only those research studies that are outlined in this protocol. * For pediatric patients: tumor biopsy/resection tissue used for pediatric preclinical model development will only be from tissue already being obtained as part of a procedure necessary for the patient s clinical care or as part of a primary research protocol; blood specimens will be collected as part of a blood collection already scheduled for the patient s clinical care or as part of the planned pre-procedure bloodwork; volumes collected will not exceed institutional research limits. * Given the risks associated with any invasive procedure, such as tumor biopsy, the procedure will be discussed in detail with the patients and their parents/guardian (as indicated), including the side effects, prior to obtaining a separate consent for each procedure. A separate consent will not be signed prior to obtaining samples by minimally invasive measures, such as venipuncture. * This study has two separate consent forms at the NIH Clinical Center: one for adult patients to donate specimens for ongoing research on assay development and studies of molecular pathways, and one for adult and age-appropriate pediatric patients to donate samples for the generation of preclinical models. The study also has consent form templates for adult and pediatric patients at participating sites to donate specimens to create preclinical models. * Patients may remain on study for the duration of their consent or completion of the planned procedure, whichever comes first.

Background: People who join a study in the Developmental Therapeutics Clinic (DTC) have tests. These include blood draws and biopsies. Researchers collect data from these samples. Some people take part in more than one study at the DTC. At this time, data are connected only with one single study. Researchers want to access people s medical records. This will allow them to link the research data from all their studies they have or will take part in. Researchers also want to collect medical data about their diagnosis and treatment history. This will allow them to see how their cancer reacted to different drugs over time. Objective: To enter people into a master protocol to connect research sample and treatment data across DTC studies. Eligibility: People ages 18 and older who are being evaluated or treated for cancer in the DTC Design: Participants will allow researchers to look at all the data from their research samples. This includes those from their current, past, and any future NIH studies. Participants will allow researchers to access some of their medical data. This includes age, diagnosis, treatment history, and response to treatment. Participants will provide no new samples. ...

The Human Observatory Study is a prospective observational and ecological surveillance study building a continuously-updating world model for human health, disease, and death at the individual and population level. Individual multi-system clinical data from enrolled participants are linked to a continuously-ingested ecological data infrastructure spanning environmental exposures, social determinants, genealogical and family history records, mortality data, and population health databases at geographic resolutions from home address to global scale and beyond. The resulting model generates individual screening recommendations informed by population-level causal estimates, and population-level causal forecasts anchored by present-timepoint individual clinical biology. This linkage creates a feedback architecture designed to improve both simultaneously.