Clinical Research Directory

Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors

AI-061 is a co-formulation drug product (DP) consisting of 1:1 ratio mix of AI-025, an anti-PD-1 antibody, and ONC-392, an anti-CTLA-4 antibody. This is a dose escalation study to identify the maximum toxicity dose (MTD) or the recommended phase 2 dose (RP2D).

Evaluation for NCI Surgery Branch Clinical Research Protocols

Background: The National Cancer Institute Surgery Branch (NCI-SB) 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 allow patients to under screening and evaluation for participation in NC-SB Protocols. Eligibility: Patients 18 years or older must meet the minimum eligibility criteria for an NCI-SB treatment protocol. Design Patients will undergo testing and evaluations as required by the appropriate NCI-SB treatment protocol. ...

A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors

The purpose of the study is to explore the safety and effects of the study drug (PF-08046876) in people diagnosed with advanced cancer of the bladder, lung, head and neck, esophagus, or pancreas. PF-08046876 is an investigational anticancer therapy called an 'antibody drug conjugate' or 'ADC'. ADCs are anticancer drugs designed to stick to cancer cells and kill them. The study drug will be given to participants through a needle in a vein (intravenous infusion). This study includes multiple parts. In the first part of the study, there will be different groups of people receiving different doses of the study drug. The study may also test different schedules.

Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy

Immunotherapy (checkpoint inhibitors) is approved as first and second line treatment to patients with metastatic bladder cancer. However, response rates are low and no biomarkers have yet shown strong predictive value for patient selection. Moreover, the term 'metastatic' is based on metastases visible on conventional CT scans and, thus, require a certain size of tumour load. Clinical trials are currently being conducted that investigate the use of adjuvant immunotherapy for this group of patients (treatment to all), which will result in massive over-treatment and huge costs to the healthcare system. This project has the primary objective to identify new indications for initiating immunotherapy in patients with metastatic bladder cancer. Sensitive molecular techniques for detection of tumor DNA in the blood will be used to identify patients with early signs of metastatic disease. In addition, comprehensive biomarker analysis will be performed to identify predictors of treatment response.

Germline Alterations of Tumor Susceptibility Genes in New York Cancer Patients

The basic premise of this research proposal is to determine whether there is any significant association between germline polymorphisms and cancers of colon, bladder, breast, testicular, prostate, ovaries, kidney, lung, lymphoid organs, and head and neck. This is an exploratory study designed to generate hypotheses for further research.

Detecting CREPT in Urine for Bladder Cancer Diagnosis and Monitoring

This study will, for the first time, establish a non-invasive diagnostic model for bladder cancer based on CREPT expression levels in exfoliated urothelial cells using a multicenter cohort, and validate its value in the non-invasive diagnosis and recurrence monitoring of bladder cancer. Its high sensitivity is expected to overcome the technical limitations of existing biomarkers and provide an innovative solution for establishing an integrated precision diagnosis and treatment system encompassing "screening, diagnosis, and monitoring."

Determinants of Bladder Cancer Recurrence Study (The DETER Study)

The purpose of this study is to learn how different lifestyle factors, such as cigarette smoking and body weight, change after a diagnosis of bladder cancer, and how they influence who gets a bladder cancer recurrence and who does not.

Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder

This study evaluates the post cystectomy CD8+ tumor response of patients receiving Nivolumab plus Urelumab versus Nivolumab alone. Half the patients will receive Nivolumab plus Urelumab, while the other half will receive Nivolumab alone.

En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device

Background: Bladder cancer is the sixth most common cancer in the United States. The way that doctors remove tumors in bladder surgeries may leave some cancer . Also, many people have their tumors return or progress after surgery. Researchers want to test a modified device. It might tell doctors more about bladder tumors. Objective: To see if using a modified standard device with bladder surgery can provide better information about tumors in bladder specimens. Eligibility: People ages 18 and older who need to have their bladder removed at the NIH. Design: Participants will be screened with: Medical and prior surgical history Review of existing MRI, x-ray, or CT scans Review of existing specimens and reports Pregnancy test for women of childbearing age CT or MRI: Participants will lie in a machine. The machine will take pictures of their body. Participants will have bladder surgery. This will occur in the same way as if they did not take part in this study. A member of the research team will cut the removed bladder using the modified device. This will most likely be done on a separate back table in the operating room. The bladder and samples after cutting will be sent out for review. The will occur just as it would if the participants were not in this study. The only difference is the way that the specimen is prepared for review. Participants follow-up care will occur per standard of care. Or it will occur as part of any other study in which they might also be enrolled.

A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors

This is a multicenter clinical study to evaluate the safety, efficacy, and Pharmacokinetics (PK) of IDE892 as monotherapy and in combination with other agents including IDE397 in participants with methylthioadenosine phosphorylase (MTAP)-deleted advanced solid tumors within indications of interest.

A Study Evaluating the Safety, Efficacy, and Pharmacokinetics (PK) of EVOLVE104 in Participants With Advanced Urothelial and Squamous Cell Carcinomas

The goal of this study is to evaluate the safety and effectiveness of EVOLVE104 in participants with advanced urothelial and squamous cell carcinomas who have previously taken standard treatment options, have declined or have been ineligible for treatment with these medications. Participants with advanced or metastatic cancer who meet all eligibility criteria may be eligible to participate in the study.

KEYMAKER-U04 Substudy 04D: A Clinical Study of New Treatments Given With Enfortumab Vedotin and Pembrolizumab in People With Urothelial Cancer (MK-3475-04D/KEYMAKER-U04)

Researchers are looking for new ways to treat people with urothelial cancer (UC) that is locally advanced or metastatic. The standard treatment for locally advanced or metastatic UC is enfortumab vedotin (EV) given with pembrolizumab. The goals of this study are to learn about: * The safety of the study treatment when given with standard treatment and if people tolerate it * The number of people who have the cancer respond (cancer gets smaller or goes away) with the new study treatment when given with standard treatment.

Care of the Urothelial Cancer Patient and Prospective Procurement of Urothelial Cancer Tissue

Background: Urothelial cancer is cancer of the bladder, ureter, and urethra. Researchers want to better understand what changes in a person s cells and genes cause this cancer to form. This may help them find new ways to treat it. Objective: \- To perform DNA sequencing to help researchers learn the differences between normal tissue and tumor tissue. Also, to learn how molecular changes - including gene changes - might help predict the course of disease and how people respond to therapy. Eligibility: \- Adults age 18 and older who have or are suspected of having urothelial cancer or an inherited disorder that raises their risk of getting bladder cancer. Design: * Participants will be screened with a physical exam. Their medical records and tissue samples will be reviewed. * Eligible participants will give tissue blocks of their original tumor. The blocks will be put in a tissue bank. * Participants medical records may be reviewed. * Participants may have a medical history and physical exam. * Participants may have blood and urine tests. They may have imaging scans. They may give urine, blood, and saliva samples. These samples may be used in future research. * If participants need surgery for their cancer, researchers will keep some of the tissue (both tumor and normal tissue). The tissue may be used in future research. * Participants will go back to the Clinical Center in 6 months. They may give saliva, urine, and blood samples. After 6 months, they will be seen by their local doctor for standard post-surgical visits. * Participants will be called every 6 months to give health updates.

A Clinical Study of MK-3120 in People With Bladder Cancer (MK-3120-003)

Researchers are looking for new ways to treat high-risk non-muscle invasive bladder cancer (HR NMIBC). NMIBC is cancer in the tissue that lines the inside of the bladder and has not spread to the bladder muscle or outside of the bladder. In standard treatment for HR NMIBC, doctors first remove the tumor with a procedure called transurethral resection of the bladder tumor (TURBT). Researchers want to learn if using MK-3120, the study medicine, can treat HR NMIBC after TURBT. The goal of this study is to learn about the safety of MK-3120 and if people tolerate it.

Exploration of Novel AI-enabled Blue Light Enhanced Cystoscopy

Blue light cystoscopy (BLC) is a diagnostic procedure in bladder cancer where the inside of the bladder is observed with a camera to detect bladder lesions. Unlike regular white light cystoscopy, blue light cystoscopy makes use of a drug that induces fluorescence under blue light preferentially in neoplastic and malignant cells that helps visualize bladder lesions during the cystoscopic procedure. Blue light cystoscopy has shown to improve detection of bladder cancer. Cystoscopy, including blue light cystoscopy, is a procedure involving assessment of the visual appearance of the bladder surface, leading to decisions of taking biopsies, remove suspicious areas and assign treatment options. The assessment is subjective and has a large operator variability. These shortcomings show an opportunity for computer aided detection (CADe) medical device to add value to both clinicians and patients. The objective of this data collection study is to build a high-quality, diverse data set of video, image recordings and relevant clinical data from BLC procedures performed as part of routine clinical practice to train a computer-aided detection (CADe) algorithm for real- time lesion detection during cystoscopy. The data will be used to support the training, non-clinical technical development and testing of such AI algorithms for use during cystoscopy and to provide documentation needed for training of such algorithms and to assist in guiding future validation of such algorithms. Exploratory purposes of the study is to use data to explore future AI algorithms in bladder cancer, such as computer-aided diagnosis (CADx) AI algorithms, image enhancement and cystoscopy improvement algorithms, including bladder mapping, tumor visualization, cystoscopy documentation, and combination models of image and clinical data including risk assessment, clinical outcomes, and disease modeling

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.

A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) to Treat Urothelial Cancer (MK-2870-031)

Researchers are looking for new ways to treat locally advanced or metastatic urothelial cancer (UC). Current treatments for locally advanced or metastatic UC include chemotherapy, immunotherapy, and targeted therapy. Researchers want to know if giving sacituzumab tirumotecan (sac-TMT), the trial medicine, can treat locally advanced or metastatic UC that got worse after certain treatments. The goal of this trial is to learn if people who receive sac-TMT live longer than those who receive certain non-platinum chemotherapies.

DESTINY-PANTUMOUR04

This study will evaluate the effectiveness of T-DXd in patients with HER2-positive (IHC 3+) locally advanced, unresectable, or metastatic solid tumors who have received prior systemic treatment for metastatic or advanced disease and have no satisfactory alternative treatment options in a real-world setting in the US

Urinary Tumor DNA-Guided Systemic Immunotherapy for Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer

This study aims to evaluate whether urinary tumor DNA (utDNA) can guide treatment duration in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) who achieve complete clinical response after systemic immunotherapy. Participants will receive systemic immunotherapy followed by response assessment using pathology, cystoscopy, urine cytology, and utDNA testing. Patients who achieve complete clinical response will receive a short additional course of immunotherapy before stopping treatment according to the study protocol. The study hypothesizes that a shortened duration of systemic immunotherapy guided by utDNA monitoring may maintain favorable oncologic outcomes in this population.

Dutasteride in Patients With Low Grade Non-muscle Invasive Bladder Cancer

Low grade non-muscle-invasive bladder cancer (NMIBC) often recurs after treatment, requiring repeated surgeries, especially in older patients. These recurrences can cause complications, reduce quality of life, and increase healthcare costs. Currently, there is no well-tolerated preventive treatment routinely used for patients with low-risk disease. This study will evaluate whether dutasteride, an oral medication that blocks androgen activity, can reduce the risk of bladder cancer recurrence. Dutasteride is generally well tolerated and easy to take. The study will also assess its safety in women. The goal of this study is to determine whether dutasteride can provide a simple and effective way to prevent recurrences of low grade non-muscle invasive bladder cancer.

Relevance of the Urine Bacterial Culture Performed Before TransUrethral Resection of the Bladder for Post-operative Febrile Urinary Tract Infections Prevention: a Non-inferiority Randomized Controlled Trial

The main objective of the study is to demonstrate that not performing a systematic UC before the TURB procedure is non-inferior to performing a systematic UC in terms of the incidence of febrile UTIs during the first 30 postoperative days

A Study of Radiation Therapy to Treat Solid Tumor Cancer That Has Spread to Soft Tissue

The purpose of this study is to find out whether lattice radiation therapy (LRT) is an effective radiation therapy technique when compared to standard stereotactic body radiation therapy (SBRT). The study will also study how the different radiation therapy techniques (LRT and SBRT) affect how many immune cells are able to attack and kill tumor cells (immune infiltration).

Bintrafusp Alfa (M7824) and PDS01ADC Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies

Background: Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug PDS01ADC triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. Objective: To learn if M7824 and PDS01ADC, with or without SBRT, can help the immune system to fight cancer better. Eligibility: People 18 and older with cancer that started in the bladder, kidneys, or other genitourinary organs (but not the prostate) and has spread to other parts of the body. Design: Participants will be screened with: medical history physical exam ability to do their normal activities blood tests urine tests electrocardiogram body scans. Participants will give a tumor sample or have a tumor biopsy. Screening tests will be repeated during the study. Participants will get PDS01ADC . It is injected under the skin every 4 weeks. They will also get M7824 through an intravenous (IV) infusion every 2 weeks. For this, a small plastic tube is put into a vein in the arm. They will get these drugs in 28-day cycles until they leave the study. They may have SBRT. Participants will give tissue and saliva samples. Participants will have a follow-up visit 30 days after treatment ends. Then they will get phone calls or emails every 12 weeks indefinitely.

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Background: Fibroblast-activation protein (FAP) is an enzyme that appears in high numbers in cancer-associated fibroblasts of certain cancer types. \[18F\]FAPI-74 is a new PET (positron emission tomography) tracer, a substance that is injected into a person s body before an imaging scan. Researchers believe that \[18F\]FAPI-74 PET imaging may be able to visualize cancer more effectively than the approved tracers. If so, the new tracer would make it easier to find FAP-positive tumors in the body. Objective: To see if \[18F\]FAPI-74 PET scan is as good or better than other imaging methods for detecting certain cancers. Eligibility: People aged 18 years or older with one of these cancer types: pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma, hepatocellular carcinoma (HCC), gastric cancer, bladder cancer, ovarian cancer, pheochromocytoma/paraganglioma (PPGL), small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancer (EP-NEC), mesothelioma or sarcoma. Participants must be scheduled or intended to receive treatment for cancer. Design: Participants will have 2 baseline scans: an \[18F\]FAPI-74, and the approved tracer \[18F\]-FDG. The \[18F\]FAPI-74 will be infused through a needle inserted into a vein. About 1 hour later, the participant will undergo imaging. Within 1 week, participants will undergo the same scanning procedures with the approved tracer. If the baseline scan with \[18F\]FAPI-74 shows the tumor(s), scans with this tracer will be repeated when their regular treatment regimen calls for scans again. If the scan with the regular FDG also show tumors, this scan will be repeated within the same week as the repeated \[18F\]FAPI-74 scan. If \[18F\]-FAPi PET scan shows no tumor(s), scans will not be repeated. If the participant's cancer progresses within 2 years, scans may be repeated. Follow-up calls will continue for 2 years.