Clinical Research Directory

Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

Background: Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths in the airways. These growths come back when removed; some people may need 2 or more surgeries per year to keep their airways clear. Better treatments are needed. Objective: To see if a drug called bevacizumab can reduce the number of surgeries needed in people with RRP. Eligibility: People aged 18 and older with recurrent RRP; they must need surgery to remove the growths in their airways. Design: Participants will be screened. Their ability to breathe and speak will be evaluated. They will have an endoscopy: a flexible tube with a light and camera will be inserted into their nose and throat. They will have a test of their heart function and imaging scans of their chest. Participants will have surgery to remove the growths in their airways. Bevacizumab is given through a small tube placed in a vein in the arm. After the surgery, participants will receive 11 doses of this drug: every 3 weeks for 3 doses, and then every 6 weeks for 8 more doses. They will come to the clinic for each dose; each visit will be about 8 hours. Tissue samples of the growths will be collected after the second treatment; this will be done under general anesthesia. Participants may undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the cells needed for the study. The remaining blood will be returned to the body through a second needle. Follow-up will continue for 1 year after the last treatment.

Better Care Closer to Home: Enhancing Primary and Community Care

60 million people in Europe have diabetes (DM) and up to 34% (20.4 million) of them are at risk of developing diabetic foot ulcers (DFUs) in their lifetime (1). However, current primary and community care is suboptimal with 40% of DFUs recurring within a year. Path Active (PA) is a digital health tool composed of smart insoles and a Bluetooth-connected app, which remotely monitors users' DFU risk, reducing their reliance on institutionalised care. This project will use interdisciplinary approaches to assess PA's ability to strengthen primary and community care systems (Subtopic 1) in culturally and socioeconomically diverse settings. We will take an ecosystem approach, incorporating multiple stakeholders including end-user patients,healthcare professionals, policy makers and potential commercial partners, investigating PA through economic, social, and clinical lenses. The project will pilot PA in \>100 individuals across 3 different countries (Canada, Denmark, and Spain) over 18 months. This will allow us to carry out: * Implementation research: Mapping PA implementation in diverse care settings, identifying local barriers to PA's adoption and necessary changes to promote PA integration into community care. * Service and ICT research: End user-testing to facilitate iterative design improvements, ensuring PA is culturally appropriate. * Health economics and policy research: Investigate international policy impact on the health economics surrounding PA and inform PA's market plan for different health systems. * Pilots: Gather evidence on PA's effectiveness in preventing DFUs and investigate/tackle any potential efficacy differences between cultures. * Business development: Scale up PA production and map potential stakeholders in member sites. Overall, STRIDE-COM represents a significant step toward integrating innovative digital health solutions into primary care across Europe/Canada, establishing a replicable model for wearable technologies.

AB-2100, an Integrated Circuit T Cell Therapy in Patients With Recurrent Clear-cell Renal Cell Carcinoma (ccRCC)

This is a multi-center, open-label phase 1/2 trial evaluating the safety and efficacy of AB-2100 cell product. The study may enroll approximately 60 patients in phase 1 and approximately 70 patients in phase 2.

Association Between Exercise, Patient-Reported Outcomes, and Clinical Events in Adult Cancer Survivors

This protocol is a retrospective study using observational data to conduct a target trial emulation to examine the association of exercise on cancer specific endpoints and other clinical outcomes in cancer survivors.

AB-1015, an Integrated Circuit T (ICT) Cell Therapy in Patients With Platinum Resistant Epithelial Ovarian Cancer

This is a multi-center, open-label phase 1 dose escalation trial that uses a modified 3+3 design to identify a recommended phase 2 dose (RP2D) of AB-1015 cell product. Backfill cohorts will enroll additional subjects at doses deemed to be safe for a total enrollment of up to 12 subjects per each backfill cohort on the protocol.

Real-world Study of SKB264 Monotherapy or Combination Therapy in Recurrent or Metastatic HER2-negative Breast Cancer

This study is a multi-center observational real-world study, with a total of 500 patients planned to be enrolled. This study is divided into two cohorts: the triple-negative breast cancer (TNBC) cohort and the hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/ HER2-BC) cohort. The aim of this study is to assess the efficacy and safety of Sacituzumab Tirumotecan (SKB264) monotherapy or combination therapy in patients with unresectable locally advanced, recurrent or metastatic HER2-negative breast cancer in the real-world setting.

Bevacizumab Alone Versus Dose-dense Temozolomide Followed by Bevacizumab for Recurrent Glioblastoma, Phase III

The aim of this Phase III study is to evaluate the superiority of dose-dense temozolomide (ddTMZ) followed by bevacizumab at ddTMZ failure for glioblastoma at first recurrence or progression, comparing to bevacizumab alone.

Vorasidenib Expanded Access Program

This is an expanded access program to provide vorasidenib for treatment of patients 12 years or older with IDH1- or IDH2-mutated glioma. For participants in Japan, DIM-95032-001-JPN will provide access to vorasidenib for Japanese participants aged 12 years and older with IDH1- or IDH2-mutant diffuse glioma who have undergone surgery as their only treatment and have no immediate need for radiotherapy and/or chemotherapy. Participants will receive vorasidenib once daily as long as they continue to see a benefit, do not experience unacceptable reactions, and vorasidenib is not commercially available by prescription. Enrollment will continue until vorasidenib is commercially available in Japan or until the study closes. Participants will transition off the study within approximately 3 months after vorasidenib becomes commercially available by prescription with local reimbursement (price listing) in Japan. A final safety follow-up visit is conducted 30 days after the last dose of treatment on the study.

Predicting Early Tumor Recurrence in Patients With Esophageal Squamous Cell Carcinoma

The prognosis of patients with esophageal squamous cell carcinoma (ESCC) who develop post-operative early tumor recurrence is often relatively poor. Therefore, biomarker that can detect micro metastases before the start of treatment is required. Epigenomic alterations such as DNA methylation have attracted attention as promising biomarkers. The investigators aim to predict early recurrence based on whole genome DNA methylation analysis of esophageal cancer.

Study to Evaluate the Efficacy of Zanzalintinib in the Treatment of Relapsed or Metastatic Adenoid Cystic Carcinomas of the Head and Neck

Adenoid cystic carcinomas are rare cancers of the salivary glands. These cancers are treated with curative surgery, often followed by radiation therapy. Despite this aggressive treatment, approximately 50% of patients will develop a recurrence or metastatic disease (spread of the disease to another part of the body). Treatment of this progressive disease with chemotherapy or targeted therapy has not demonstrated significant efficacy so far, and there are currently no management recommendations from health authorities. The emergence of new drugs offers hope for patients. Zanzalintinib, thanks to its specific mechanisms of action, could be an effective treatment for patients whose disease has progressed.

Non-Thermal Plasma to Reduce Recurrence in Chronic Subdural Hematoma

The goal of this randomized controlled trial is to evaluate whether the adjuvant application of non-thermal plasma (NTP) during standard surgical drainage of chronic subdural hematoma (cSDH) can reduce the recurrence rate at 6 months. The main questions it aims to answer are: * Does NTP application significantly lower the radiological and clinical recurrence rate of cSDH compared to surgery alone? * Is NTP safe when applied to the subdural space and surgical wound bed? * Does NTP improve functional outcomes and time to hematoma resolution? Participants will be randomly assigned to one of two groups: * Experimental group (n = 20): Standard burr hole drainage or craniotomy plus intraoperative NTP application over the exposed dura mater, the residual membrane, soft tissue layers, and the skin incision. * Control group (n = 20): Standard surgical drainage alone (no NTP). Follow-up includes clinical assessments and computed tomography (CT) scans at 1 week, 3 months, and 6 months post-surgery. The primary outcome is recurrence (symptomatic reaccumulation requiring re-intervention or ≥50% volume increase on CT).

Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors

The goal of this clinical trial is to learn if intratumoral administration of DNX-2401 works to treat recurrent and refractory high grade brain tumors in children and young adults. It will also learn about the safety of DNX-2401. The main questions it aims to answer are: * Does a single intratumoral administration of DNX-2401 elicit tumor response and improve survival? * Is a single intratumoral administration of DNX-2401 safe and well tolerated? Participants will: * Undergo surgery for tumor biopsy followed by a single intratumoral administration of DNX-2401 * Visit the clinic periodically for checkups and tests

xDRIVE for Florida-based Cancer Patients

Through this study funded by the Florida Cancer Innovation Fund, First Ascent will demonstrate state-wide feasibility of providing xDRIVE Functional Precision Medicine + Artificial Intelligence platform by assessing patient clinical benefit and health economics impacts. As this is a feasibility study, results will be returned to the physician and the physician may use the data to inform the next line of treatment. The investigator will run a prospective single-arm feasibility study providing the xDRIVE FPM AI platform to n = 210+ cancer patients throughout the state of Florida, especially those from underserved populations (pediatric patients and patients in Black, Brown, Hispanic, and rural communities).

Circulating Tumor DNA Based Adjuvant Chemotherapy in Stage II Colon Cancer Patients: the MEDOCC-CrEATE Trial

Patients in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) with non-metastatic colon cancer that gave consent for additional blood withdrawals are enrolled in the observational PLCRC-MEDOCC substudy. In this study, blood is collected before surgery, after surgery and during follow-up. Within PLCRC-MEDOCC, patients with stage II colon cancer that are not considered to have an indication for adjuvant chemotherapy, can be included in the MEDOCC-CrEATE subcohort under the condition that they gave informed consent in PLCRC for biobanking of tissue and for future studies (Trial within Cohorts design). Patients included in MEDOCC-CrEATE will be randomized 1:1 to the (A) ctDNA-based treatment group versus (B) the standard of care group. A total of 1320 patients will be randomized. Patients randomized to the ctDNA-based treatment group will have their post-surgery samples analysed directly after informed consent for MEDOCC-CrEATE. All patients with detectable ctDNA will be offered adjuvant chemotherapy (3 months CAPOX). Patients with undetectable ctDNA will receive routine follow-up at the surgical department. The aim of this Trial within Cohorts study is to investigate how many patients with detectable ctDNA after surgery start with adjuvant chemotherapy.

Study of the Impact on the Evolution of the Disease in the Medium Term of the Implementation of a System of Extended Follow-up by Telephone Interview of Patients With an Eating Disorder Organized by the Nurses of the Eating Disorder Referral Center

The referral center for eating disorders provides for a systematic many years follow-up of patients under care with an annual assessment at the center. The investigators have recently shown the frequency of relapse in the first 7 years after diagnosis, but the literature remains poor on this epidemiology and on the risk factors for relapse. The investigators would therefore like to extend this follow-up for an additional 3 years after remission with an annual telephone nursing interview for all cured patients.

The Effectiveness and Safety of Body Posture in Preventing Postoperative Recurrence for Chronic Subdural Hematoma

This study aims to investigate the effectiveness and safety of body posture to improve intracranial pressure in preventing postoperative recurrence for chronic subdural hematoma

Holmium Laser Versus Cold Knife Treatment in Urethral Strictures

The goal of this study is to assess the efficacy of optical internal urethrotomy, which uses a holmium laser in comparison to a cold knife, in treating short-segment urethral strictures in our local setting. The study will help standardize treatment protocols for urethral stricture based on functional results. The local findings will encourage adoption of minimally invasive laser techniques in public hospitals, improving access to modern urologic care. The study will help in informed decision making, enabling patients to understand treatment options and their expected outcomes based on evidence.

Fecal Microbiota Transplant vs Standard Treatment for Recurrent Non-Obstructive Cholangitis

Patients with abnormalities of the biliary tract (the system that connects the liver to the small intestine and allows bile to flow) are prone to the development of strictures, dilations, or other problems that impede bile flow and promote the formation of gallstones. All of this leads to the development of infections in this anatomical region known as cholangitis. These infections typically require the patient to be admitted to the hospital, either to a general ward or even the ICU. These are, therefore, serious infections that threaten the patient's survival. Unfortunately, one-quarter of these patients experience not just one, but multiple infections of this type over an extended period of time. This condition is called acute recurrent cholangitis (ARC). It is important to note that the antibiotics used to treat these repeated infections lead to the selection of more resistant and virulent bacteria that remain in the intestine for months or years and, in turn, promote the recurrence of these infectious episodes. ARC affects a more vulnerable population, which, combined with the proliferation of resistant bacteria, increases the risk of serious complications and a reduced response to available treatments. Replacing these dangerous gut bacteria with bacteria from healthy donors is a strategy that has proven effective in reducing recurrent urinary tract infections. A similar approach has been successful in patients with chronic vaginal infection (vaginosis). This gut microbiota replacement is currently being investigated for a wide range of diseases affecting various sites, with promising results in some cases. There is strong evidence that this strategy may also be effective in patients with recurrent episodes of cholangitis. The procedure is considered very safe and is subject to strict safety measures to prevent risks to the recipient of these bacteria (requirements similar to those used for blood transfusions). If this strategy proves effective, it could reduce patient suffering and even mortality, as well as save money spent on hospital stays and medications, and contribute to reducing antibiotic use and the emergence of bacterial resistance. Even if no significant clinical benefit is demonstrated in this clinical setting, the information obtained will contribute to increasing knowledge about the role of the fecal microbiota, the technical and scientific aspects of fecal microbiota transplantation, and its potential uses. It should be noted that a patient association called ALBI España (Association for the Fight Against Inflammatory Biliary Diseases) has participated in the study's design and strongly supports this research, which could lead to a reduction in mortality among its patients and a reduction in adverse effects and costs associated with hospital admissions and antibiotic use. In summary, the use of FMT in patients with AC could have a significant impact on treatment effectiveness, reducing new episodes of cholangitis. This would improve patients' quality of life-including their physical, emotional, and social well-being-by reducing hospitalizations and associated complications. Another clear benefit would be the reduction in the proliferation of resistant bacteria and a lower use of antibiotics. The use of TMF would increase the autonomy of the National Health System (SNS) by enabling it to develop and manage non-commercial, non-profit therapies with low production costs, which would guarantee equitable access for patients to an effective and safe therapy.

Early Detection of Metastatic Recurrence Among Patients With Stage II or III Triple Negative Breast Cancer Using Liquid Biopsy and Imaging

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, often with poor outcomes. Currently, follow-up for TNBC consists of physical exams and annual breast imaging, with additional scans only if symptoms appear. This approach may delay the detection of the cancer coming back until the disease is advanced. A promising new technique is the detection of circulating tumor DNA (ctDNA)-in the blood. Studies suggest ctDNA may identify cancer recurrence months before it becomes visible on scans or causes symptoms. However, it is unknown whether detecting recurrence earlier can actually help patients live longer or feel better. The EINSTEIN-TNBC trial is a study aiming to evaluate the feasibility of ctDNA-guided surveillance for patients with TNBC after surgery. Thirty participants will be randomized to either: Standard of care (routine physical exams and annual breast imaging), or Active surveillance (standard of care plus ctDNA testing, with imaging investigations if ctDNA is detected). This study will assess the feasibility of conducting a ctDNA-based monitoring trial in this patient population. If feasible, EINSTEIN-TNBC will lay the foundation for a larger future clinical trial to determine whether earlier detection of metastatic TNBC can improve survival and quality of life.

Clinical Trial Assessing the Safety and Immunologic Correlates of Heterologous Prime-Boost With pNGVL4a-Sig/E7(Detox)/HSP70 and TA-HPV in Healthy Donors Followed by Peripheral Blood Collection

This healthy related donor clinical trial is linked to a recipient clinical trial protocol for therapeutic purposes. In this healthy donor protocol, haploidentical relatives of a patient with recurrent or metastatic human papilloma virus (R/M HPV) 16-associated malignancy will be invited to be vaccinated with a therapeutic HPV vaccine series (PVX1) to generate HPV-specific white blood cells. In the linked recipient phase 1 clinical trial protocol, patient with incurable, locally recurrent or metastatic HPV 16-associated head and neck cancer will be randomized to one of two arms: Arm A: non-myeloablative (NMA) allogeneic bone marrow transplant (alloBMT) OR Arm B: CD8-depleted donor lymphocyte infusion (DLI) on Day 0 of a dose escalation scheme These two clinical trials are separated so that the healthy donor trial deals exclusively with issues of safety and immunological efficacy of the HPV vaccine series and this companion recipient trial examines the safety, feasibility and clinically efficacy of the allogeneic bone marrow graft and CD8-depleted DLI. The central hypothesis of the clinical trial is that patients with R/M HPV-associated malignancies can be safely and effectively treated by allogeneic bone marrow transplantation and/or CD8-depleted DLI from a healthy related donor that has been vaccinated against HPV16 E6 and E7 proteins.

Evaluation of Outcomes of the Triathlon Hinge Knee (THK) System

This study is a prospectively and retrospectively enrolled, post-market, open-label, non-randomized, single institution evaluation of clinical outcomes of primary or revision knee surgery patients who meet the eligibility criteria and received devices from the Triathlon Hinge Knee System according to its indications for use (IFU). Clinical evaluation for all cases will include data collection of patient demographics, surgical details, early postoperative status, functional and clinical outcomes, and survivorship at 1, 2, 6, and 10-years.

Development and Clinical Validation of Early-stage Lung Cancer Prognostic Kit

Lung cancer is the leading cause of cancer mortality worldwide in spite of the advanced progresses in medication and low-dose CT screening. The early-stage lung cancer accounts for less than 50% of newly diagnosed lung cancer in Taiwan, even in stage IB patients proximately 30% still suffer from recurrence and metastasis. The International Cancer Moonshot Project recently established the first comprehensive proteogenomics profiling of early-stage lung cancer patients in East Asia, revealing a proteomics-informed classification to identify a new "late like" subtype, which can identify a subgroup of early-stage patients with worse clinicopathological features (Cell, Cover story, 2020). This study has been featured in prestigious journals (Nat Rev Clin Oncol; Cancer Discov, 2020) and led to two provisional US patents. In this proposal, taking the discovery from the Cancer Moonshot multiomics database, the investigators aim to translate these findings into clinical utilities. Two subprojects are proposed. (1) Validation of "late-like" protein markers for identifying high-risk early-stage lung cancer: Two IVD kits will be developed, including high-risk early-stage lung cancer IHC prediction kit for tumor staining and high-risk early lung cancer ELISA prediction kit for noninvasive diagnosis. (2) Conducting a prospective clinical trial to evaluate the accuracy of high-risk early-stage lung cancer IHC prediction kit and high-risk early-stage lung cancer ELISA prediction kit.

Adjuvant Anti-PD-1 Therapy in Resected Hepatocellular Carcinoma

Early hepatocellular carcinoma (HCC) recurrence (driven by residual tumors) and late recurrence (driven by de novo tumors) exhibit distinct biological behaviors, suggesting differential therapeutic vulnerabilities. The beneficiaries of adjuvant PD-1 inhibitors (aPD-1) and their efficacy across these temporally divergent recurrence patterns remains unestablished.

Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in HCC

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. While curative resection is pivotal, high postoperative recurrence rates remain a major challenge. Adjuvant immune checkpoint inhibitors (ICIs) show promise in improving outcomes, but biomarkers to identify patients who will benefit are lacking. Current clinicopathological risk factors for minimal residual disease (MRD) are suboptimal in sensitivity and specificity. Circulating tumor DNA (ctDNA) analysis, reflecting real-time tumor dynamics, offers a promising approach for MRD detection. This study focuses on the methylation status of GNB4 and Riplet-genes located within HCC-associated CpG islands-using a bespoke bisulfite-conversion and qPCR assay to sensitively detect methylated alleles, thereby enabling MRD monitoring. To clinically validate this approach, we will conduct a prospective, multicenter cohort study assessing the predictive value of serial \*GNB4/Riplet\* methylation testing for recurrence and adjuvant therapy benefit.