Bethesda

Background: Radiotherapy is a highly effective treatment for localized prostate cancer; however, recurrence is more common in patients with unfavorable intermediate and high-risk prostate cancer, and is usually diagnosed by rising prostate specific antigen (PSA - biochemical failure). Early identification of disease persistence or recurrence before meeting criteria of biochemical failure may allow effective potentially curative salvage treatment, but identification of local recurrence or persistence at early stages is challenging. CT imaging is relatively insensitive at localizing recurrence, while MRI is more sensitive for local recurrence but is non-specific. Prostate specific membrane antigen (PSMA) targeted PET imaging was recently FDA approved for imaging men with suspected prostate cancer metastases who are potentially curable by radiation or surgery. PSMA based imaging has been used in prospective trials to define extent of disease and to alter radiation treatment volumes. 18F-DCFPyL, a second generation PSMA PET agent that binds with high affinity to PSMA yet clears rapidly from the blood pool, has recently been approved by the FDA as a method to stage high risk cancer and detect recurrent disease. Primary Objective: To define 18F-DCFPyL PET/CT imaging response in participants with localized prostate cancer after treatment with stereotactic body radiation therapy (SBRT) with or without androgen deprivation therapy (ADT). Eligibility: Biopsy proven localized prostate cancer in whom prostate SBRT with or without ADT is appropriate therapy Must have at least 1 MRI detected, biopsy proven site of prostate cancer. ECOG 0-2 Design: This is a single center, prospective study aimed at recruiting the following cohorts: Up to 40 evaluable participants with presumed localized prostate cancer (intermediate or high risk) scheduled to undergo radiotherapy with systemic androgen deprivation therapy. Up to 40 evaluable participants with presumed localized prostate cancer (intermediate or high risk) scheduled to undergo SBRT without androgen deprivation therapy. Up to 20 evaluable participants with presumed localized prostate cancer (intermediate or high risk) scheduled to undergo radiotherapy with localized androgen deprivation therapy. Participants receiving neoadjuvant androgen deprivation therapy will undergo a second 18F-DCFPyL PET/CT and multiparametric MRI (mpMRI) at 8 weeks after initiation of ADT but before SBRT. All participants will undergo 18F-DCFPyL PET/CT and mpMRI 6 months following completion of SBRT and at recurrence, if applicable. Participants will be followed for up to 2 years after completion of SBRT to evaluate longitudinal quality of life and biochemical control.

Researchers are evaluating the use of a new PET imaging tracer called [18F]FAPI-74 to detect various types of cancer. This tracer targets fibroblast-activation protein (FAP), which is found in high amounts in cancer-associated fibroblasts present in many tumors. The study aims to compare [18F]FAPI-74 PET imaging to the standard imaging tracer 18F-fluorodeoxyglucose (18F-FDG) and other standard imaging methods like CT and MRI in people with cancers such as pancreatic ductal adenocarcinoma, cholangiocarcinoma, hepatocellular carcinoma, gastric, bladder, ovarian cancers, pheochromocytoma/paraganglioma, small cell lung cancer, extrapulmonary neuroendocrine cancer, mesothelioma, and sarcoma. Participants will receive an intravenous dose of [18F]FAPI-74 before undergoing PET/CT imaging. Each participant will have two baseline scans: one with [18F]FAPI-74 and one with the standard 18F-FDG tracer, done within one week of each other. If the initial [18F]FAPI-74 scan shows tumors, further scans with this tracer will be done at times corresponding to routine cancer restaging. If the tumors are also detected by 18F-FDG, repeat scans with this tracer will be scheduled within the same week as the repeated [18F]FAPI-74 scan. Participants with negative baseline scans will not have repeated scans but will remain in follow-up. During the study, participants will be monitored with scans and follow-up calls for up to two years to assess cancer progression and survival. Researchers will measure outcomes such as the average number of lesions at baseline, after treatment, and if cancer recurs. The study includes safety monitoring with regular assessments and imaging to detect changes or progression of disease over time.

Multiple myeloma (MM) is a cancer of plasma cells that currently cannot be cured and often returns after treatment. Researchers are studying whether a new imaging agent called 18F-fluciclovine is better than the standard 18F-FDG tracer at detecting MM. The goal is to improve early identification of disease relapse, which is critical for timely treatment. This is a phase 2, open-label study including adults with newly diagnosed or relapsed/refractory MM. Participants will receive injections of 18F-fluciclovine and undergo PET/CT scans using both 18F-fluciclovine and 18F-FDG at three time points: baseline, after treatment or 6 months later for relapsed cases, and at 5 years or upon disease progression. Some participants may also have an optional MRI scan and a bone marrow biopsy at each visit. The 18F-fluciclovine dose is approximately 370 MBq given intravenously. During the study, participants will have three visits spread over up to 5 years. Each visit includes two PET/CT scans, optional MRI, and bone marrow biopsy. The study will compare the ability of the two tracers to detect disease. Researchers will also collect blood tests and monitor health status. The primary goal is to determine how well the new tracer matches the current standard in detecting MM.

Background: Methylation-mediated silencing of genes is an epigenetic mechanism implicated in carcinogenesis; agents that inhibit this mechanism are of clinical interest because of their potential to re-activate silenced tumor suppressor genes. Two DNA hypomethylating nucleosides, 5-azacytidine (azacytidine) and 5-aza-2'-deoxycytidine (decitabine) have been approved by the FDA for the treatment of patients with myelodysplastic syndromes and certain leukemias. The nucleoside analog 5-aza-4 -thio-2 -deoxycytidine (Aza-TdC) is incorporated into DNA, where it engages the active site of DNA methyltransferase I (DNMT1), a maintenance methyltransferase that contributes to the hypermethylation and silencing of tumor suppressor genes. DNMT1 can become trapped in a covalent complex with DNA, thus depleting free enzyme and inhibiting the normal maintenance methylation of CpG sites, resulting in re-activation of tumor suppressor genes. Data suggest a correlation between Aza-TdC activity in solid tumor xenograft models and decreased levels of DNMT1. Aza-TdC offers an improvement over traditional DNA methyltransferase inhibitors by virtue of a higher incorporation rate into DNA at lower levels of cytotoxicity; Aza-TdC has greater antitumor activity than another recently developed DNMT1 inhibitor, TdCyd, in some solid tumor xenograft models. Treatment with Aza-TdC is anticipated to result in the inhibition of tumor growth due to DNMT1 depletion at oral doses that are well tolerated in extended dosing schedules. Primary Objective: To establish the safety, tolerability, and MTD of oral Aza-TdC administered daily for 5 days a week for 2 weeks, with one week off, q 21-day cycles, to patients with refractory solid tumors Secondary Objectives: To determine the pharmacokinetics of oral Aza-TdC To document preliminary evidence of Aza-TdC activity To determine effect of study treatment on re-expression of select genes silenced by methylation in circulating tumor cells To determine the effects of Aza-TdC on DNA damage response (DDR) signaling and on genome-wide DNA methylation in tumor biopsy tissue Exploratory Objective: To determine the effects of Aza-TdC on global RNA expression and on levels of DNMT1, DNMT3a, DNMT3b, and other select proteins in tumor biopsy tissue To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with Aza-TdC response or resistance Eligibility: Patients \>= 18 years of age must have histologically documented solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy Study Design: Aza-TdC will be administered orally once a day for 5 days of each week for 2 weeks, with one week off, in 21-day cycles. The trial will follow an accelerated titration design, changing to a traditional 3+3 dose escalation design (3-6 patients per cohort) once specified toxicity criteria are met. Intrapatient dose escalation will be allowed. Blood samples will be obtained for pharmacokinetic analysis and to isolate circulating tumor cells to assess re-expression of genes silenced by methylation. Up to 21 patients will be accrued to a PD expansion cohort at the MTD to further assess pharmacodynamic endpoints in tumor and blood.

Researchers are investigating whether the enzyme phosphodiesterase 4B (PDE4B) is reduced in the brains of people with major depressive disorder (MDD) during a major depressive episode (MDE). This study focuses on comparing PDE4B levels between individuals experiencing MDEs and healthy volunteers. It also aims to find the best scanning duration and evaluate the reliability of a radioactive tracer called [18F]PF-06445974 used in PET scans, as well as to explore if PDE4B binding relates to clinical symptom ratings and whether it can be blocked by the drug apremilast. Participants will undergo up to five clinic visits that include physical exams, blood tests, heart function tests, and psychiatric assessments. Brain imaging involves magnetic resonance imaging (MRI) and positron emission tomography (PET) scans using the injected radioactive tracer [18F]PF-06445974. The PET scan lasts up to four hours with a break and includes monitoring of vital signs and arterial blood sampling. Some participants may have a second PET scan, a lung scan immediately after the brain scan, or receive oral apremilast to study its effect on PDE4B binding. During the study, participants will be closely monitored with clinical assessments and imaging procedures to measure PDE4B distribution volume in the brain over 36 months. Researchers will also observe the tracer’s reliability, scan length, and its relationship with clinical symptoms. Safety monitoring includes blood pressure, heart rate, breathing, and laboratory tests. Participation involves travel to the NIH and adherence to study procedures over several visits.

Researchers are investigating a targeted therapy called [212Pb]VMT-Alpha-NET for people with certain metastatic or inoperable tumors that have high levels of somatostatin receptors (SSTRs). These tumors include gastrointestinal neuroendocrine tumors, pheochromocytoma/paragangliomas, small cell lung cancers, kidney cancers, and specific head and neck cancers. The study aims to determine the maximum tolerated dose and safety of this new treatment. Participants will receive [212Pb]VMT-Alpha-NET intravenously on the first day of four cycles, each lasting 8 weeks. Some participants will also receive a related imaging drug, [203Pb]VMT-Alpha-NET, a few days before the first two treatment cycles to track drug distribution using whole-body scans. After each treatment dose, participants will stay in the hospital for a few nights and have weekly blood tests during the cycles. Throughout the study, participants will undergo physical exams, blood and urine tests, heart function tests, imaging scans, and possibly tumor tissue collection. Researchers will monitor side effects and drug safety for up to 3 years after treatment, with follow-ups continuing up to 6 years to assess long-term health and survival. The main outcomes measured include dose-limiting toxicities and all treatment-related side effects.

Researchers are gathering data and biological samples from people aged 3 to 100 years who have allergic or sinus diseases, including conditions like asthma, eczema, and allergic rhinitis. The study aims to learn more about these conditions by creating a repository of clinical, laboratory, and diagnostic information. This repository will help support research and recruit participants for related clinical studies. Participants will visit the NIH Clinical Center for evaluations and sample collections. Samples collected include blood, nasal brushings and fluids, skin swabs, urine, and occasionally tissue biopsies during routine medical procedures. Allergy skin prick tests and lung function tests will also be performed. Visits will include a baseline, annual follow-ups, and an end-of-study visit, lasting between 1 and 3 years. During their participation, individuals will complete questionnaires about their symptoms and health. Data from physical exams, nasal endoscopies, and other clinical tests will be gathered. Samples and data not used in clinical care will be stored for future research. The primary goal is to create a long-term resource of information and specimens from people with allergic and atopic diseases, with safety and treatment continuing under their regular healthcare providers.

Researchers are investigating whether patients treated for Lyme disease with antibiotics still have active bacteria causing their symptoms. The study focuses on individuals with post-treatment Lyme disease syndrome (PTLDS) and various control groups, including those with chronic Lyme arthritis, seropositive controls without symptoms, recovered controls, multiple sclerosis patients, and healthy volunteers. The goal is to better understand persistent symptoms after treatment and to develop clear diagnostic criteria and future treatment plans. Participants include people aged 13 and older with PTLDS and 18 and older for other groups. The study involves physical exams, blood tests including genetic immune system markers, leukapheresis to collect white blood cells, lumbar punctures to collect spinal fluid, brain MRI scans, neuropsychological tests, hearing tests, and urine collection. Those testing positive for Lyme bacteria may receive antibiotic treatment and have follow-up visits at 1 week, 3, 6, and 12 months, including repeated scans and tests. Participants will be evaluated regularly with blood and urine tests, imaging, and neurological assessments to monitor infection status and treatment response. Some groups will be reevaluated every 6 to 12 months. The study aims to build a detailed database of patient information to support future research and improve care for those with persistent Lyme disease symptoms.

Researchers are evaluating a culturally-tailored, home-based physical activity program designed to improve physical fitness in Hispanic or Latino/Latina adolescent and young adult childhood cancer survivors. These survivors may face long-term effects such as weight gain, fatigue, and reduced fitness after cancer treatment, with Hispanic or Latino/Latina individuals potentially at higher risk. The study aims to increase moderate to vigorous physical activity (MVPA) through a mobile health and social media intervention. The study has two stages. Stage 1 involves developing the intervention using feedback from 20 Latinx survivors who speak either English or Spanish. Stage 2 is a randomized controlled trial comparing the intervention group with a control group that only uses a Fitbit tracker. The intervention group receives Fitbit trackers, weekly reminders, goal-setting sessions, social media peer support 2-3 times a week, badges, monthly Zoom meetings, and may choose a physical activity partner who also receives support. After 12 weeks, a 4-week maintenance phase continues these supports with less structure. The control group wears a Fitbit daily for 12 weeks without additional support. Participants wear Fitbit trackers daily, attend weekly sessions, post on social media, and complete interviews and questionnaires. Researchers measure changes in physical activity levels, sedentary time, quality of life, and cardiometabolic health indicators. Data is collected using Fitbit devices, interviews, and surveys, with follow-up over 12 weeks plus maintenance. Safety and acceptability of the intervention are also assessed throughout the study.

Researchers are evaluating the safety and tolerability of GIGA-564, a minimally blocking anti-CTLA-4 monoclonal antibody, in participants with locally advanced or metastatic solid tumor malignancies. This Phase 1 study aims to identify the maximum tolerated dose and the recommended Phase 2 dose of GIGA-564 for these patients who have tumors not suitable for standard treatment or who have relapsed after prior therapies. Participants receive GIGA-564 through intravenous infusion. The study includes a dose escalation phase to determine safe dosing levels, followed by an expansion phase. Women who can become pregnant must use highly effective contraception. The study excludes participants who recently received certain cancer therapies or have specific medical conditions that could increase risk. During the study, participants will be monitored for treatment-emergent adverse events, including serious and dose-limiting toxicities, over up to 154 days. Evaluations include imaging to measure disease, ECGs, and laboratory tests to assess organ and marrow function. Researchers will track safety, tolerability, and any side effects experienced, with follow-up visits to ensure participant well-being throughout the treatment period.