Clinical Research Directory

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.

A Study to Evaluate the Safety and Efficacy of Intracranial Venous Blood Sampling for Liquid Biopsy in the Diagnosis of Brain Cancers

To learn if drawing blood directly from veins inside the brain is safe and can effectively provide the same kind of detailed information about high-grade glioma as traditional surgical biopsy.

Guiding Value of Urinary Tumor DNA Testing in Cystoscopy for High-Risk/Very High-Risk Non-Muscle-Invasive Bladder Cancer

Non-muscle-invasive bladder cancer (NMIBC) is usually treated with surgery to remove the tumor (transurethral resection of bladder tumor, or TURBT), often followed by bladder-instilled medications to reduce the chance of the cancer coming back. Even with this treatment, high-grade NMIBC can return or progress, so patients need regular check-ups, usually with cystoscopy (a camera examination of the bladder) and urine cytology. Cystoscopy is effective but invasive, can cause discomfort, and carries risks such as infection and bleeding. This makes follow-up costly and sometimes burdensome for patients. This study is testing whether a urine tumor DNA (utDNA) test - a type of "liquid biopsy" that detects cancer-related DNA changes in urine - can help guide the timing of cystoscopy for people with high-risk or very high-risk NMIBC. utDNA testing is non-invasive and has shown high accuracy in detecting bladder cancer, sometimes spotting signs of recurrence earlier than standard methods. By combining utDNA testing with cystoscopy, we hope to safely reduce the number of unnecessary cystoscopies without missing cancer recurrences. The study will evaluate whether this approach can make bladder cancer follow-up more comfortable, more precise, and more efficient.

The Guiding Value of Liquid Biopsy Based on Urinary Tumor DNA/RNA in the Second Transurethral Resection of High-risk Non-muscle Invasive Bladder Cancer

High-risk non-muscle-invasive bladder cancer (NMIBC) carries a substantial risk of residual disease after initial transurethral resection of bladder tumor (TURBT). Current guidelines recommend a second TURBT (re-TURBT) within 2-6 weeks for patients with stage T1 disease to remove residual tumor, confirm staging, and obtain additional pathological information. However, the actual survival benefit of routine re-TURBT for all high-risk patients remains debated, and the procedure may pose surgical risks, increase healthcare costs, and impact patient quality of life. Urine tumor DNA (utDNA) and urine tumor RNA (utRNA) are molecular biomarkers detectable through non-invasive "liquid biopsy" methods. In urothelial carcinoma, tumor-derived nucleic acids can be shed into urine, where they can be detected with high sensitivity and specificity. These biomarkers may help identify patients most likely to harbor residual disease after initial TURBT, and thus most likely to benefit from re-TURBT. This prospective, open-label, observational, single-center study aims to evaluate the clinical value of utDNA/utRNA testing in guiding re-TURBT for patients with high-risk NMIBC. The study will assess whether molecular urine testing can improve patient selection for re-TURBT, potentially reducing unnecessary procedures while maintaining oncological safety.

Guiding Value of Urinary Tumor DNA Testing in Repeat Transurethral Resection of Non-Muscle-Invasive Bladder Cancer

Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 75% of newly diagnosed bladder cancers and is characterized by a high risk of recurrence and progression. Current guidelines recommend that patients with stage T1 NMIBC undergo a second transurethral resection of bladder tumor (re-TURBT) within 2-6 weeks after the initial surgery to remove residual tumor, confirm staging, and obtain additional pathological information. However, the benefits of routine re-TURBT for all high-risk patients remain controversial, as many patients may not have residual disease, while the procedure carries surgical and anesthetic risks, physical and psychological burden, and additional healthcare costs. Urine tumor DNA (utDNA) refers to DNA fragments shed by tumor cells into urine. It can be detected using molecular assays with high sensitivity and specificity, offering a non-invasive method for bladder cancer diagnosis and surveillance. Previous studies have shown that positive utDNA results after initial TURBT may be associated with residual disease and higher recurrence risk. This multicenter, randomized controlled trial aims to evaluate whether utDNA testing can accurately identify NMIBC patients who are most likely to benefit from re-TURBT, thereby guiding the decision to perform the procedure. The goal is to optimize patient selection for re-TURBT, reduce unnecessary surgeries, and improve patient quality of life while maintaining oncologic safety.

Using Liquid Biopsy Testing to Identify, Monitor, Predict Recurrence in Urothelial Carcinoma

Application of Multi-Component Liquid Biopsy (ctDNA, utDNA, Exosomes, and Protein Biomarkers in Blood and Urine) for Auxiliary Diagnosis, Therapeutic Response Evaluation, and Recurrence Monitoring in Urothelial Carcinoma

Liquid Biopsy in Early Colorectal Lesions

Early colorectal cancer screening increasingly detects small superficial colonic lesions, but current diagnostic tools still struggle to distinguish benign from malignant lesions and to assess lymph node risk. As histology after resection has limited accuracy, many patients undergo unnecessary surgery. Liquid biopsy, analyzing circulating biomarkers such as tumor DNA, extracellular vesicles, and nucleosomes, offers a non-invasive way to better classify these lesions. Emerging evidence suggests it may outperform current criteria for predicting lymph node involvement in T1 colorectal cancer. This study will establish a biobank of 1,000 patients to identify blood-based signatures that predict tumor stage and lymph node status. The hypothesis of the study is that circulating biomarkers can accurately differentiate benign from malignant lesions and identify patients with or without lymph node metastasis.

A Prospective Feasibility Study Evaluating Extracellular Vesicles Obtained by Liquid Biopsy for Neoadjuvant Treatment Response Assessment in Rectal Cancer

Routine clinical and radiological assessment of response of patients with rectum cancer to neoadjuvant chemoradiotherapy does not allow accurate identification of complete pathological response, and leads to frequent false positive and negative results. Molecular markers reflecting the initial and post-nCRT status of the tumor would be ideal to select patients eligible for organ preservation. This project will test the detection of tumor extracellular vesicles (EVs) in liquid biopsy as a reliable marker for the identification of poor versus good responders to nCRT.

French Assessment of MRD by Liquid Biopsies in Stage III CRC Patients (FRENCH.MRD.CRC)

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for colorectal cancer, the methods used to decide who gets additional post-surgery treatment are suboptimal. Some patients get too much treatment, while others do not get enough. There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment after surgery. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points. The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient. FRENCH-MRD-CRC is the French study of the european GUIDE.MRD project.

French Assessment of MRD by Liquid Biopsies in PDAC Patients (FRENCH.MRD.PDAC)

The overall objective of this GUIDE.MRD consortium is to confirm that ctDNA detected after curative intended treatment for PDAC is a marker of residual disease and for risk-of-recurrence, and applicable in clinical practice. Primary objective To confirm that ctDNA analyses performed after PDAC treatment can identify patients with a high risk-of-recurrence. Specifically, the investigators want to determine the association between disease-free survival (DFS) and ctDNA detection status after 1. curative-intended surgery and 2. adjuvant chemotherapy. FRENCH.MRD.PDAC is the French study of the european GUIDE.MRD project

Liver Cancer and Immunotherapy in the Liquid Biopsy Era

The goal of this prospective clinical trial is to identify a predictive biomarker in patients with advanced HCC (stage B and C) using a combinatorial approach of the liquid biopsy. The main questions it aims to answer are: * Is multi-omic liquid biopsy approach able to identify a strong predictive biomarker of immunotherapy efficiency? * Is there a correlation between tissue biopsy (PD-L1 tissue level of expression) and liquid biopsy (detection of CTC expressing PD-L1) in HCC patients? Participants blood will be collected at several time points.

BRAINFUL (BRAIN Tumor Focused Ultrasound-enabled Liquid Biopsy) Trial

Background: Accessing brain tumor material for pathological diagnosis requires invasive procedures that carry risk to patients including brain hemorrhages and death. Liquid biopsies are emerging non-invasive alternatives to direct tumour biopsies but the abundance of circulating tumor DNA (ctDNA) is relatively low and this limits our ability to accurately make the molecular diagnosis of brain tumors. We have recently shown promising results that suggest that the analysis of blood samples can distinguish brain tumor types. We now want to couple liquid biopsies with high intensity focused ultrasound (HIFU) to enhance the release of tumor DNA into the circulation and increase the sensitivity/and specificity of liquid biopsies for brain tumors. The aim of this project is to build on our preliminary findings and investigate the the time dependent changes associated with HIFU of a tumor to see if it improves accuracy of diagnosis and specifically molecular subtyping of tumors based on peripheral blood and cerebrospinal fluid (CSF) circulating tumor derived markers following HIFU.

Versatile Ampification Single-Molecule Detection in Liquid Biopsy

The trial will test a paradigm-changing in vitro diagnostic device for Liquid Biopsy enabling facile simultaneous detection of protein and nucleic acid analytes with sensitivity at single-molecule level, e.g. not achievable with any alternative technology. A novel affinity-mediated transport amplification (AMT) method will be tested allowing for the multiplexed quantification of rare biomarkers circulating in blood. The Versilib AMT photonic biosensor will test two analytes: the known actionable DNA mutation BRAF p.V600E, and a melanoma-restricted protein antigen. The results will be compared to digital PCR and ELISA methods.

Clinical Studies of Endometrial Cytology and Cervical Methylation Assays in Endometrial Cancer Screening and Fertility-Preservation Evaluation

The current study aims to assess high-risk patients using both liquid-based cytology and cervical methylation testing. The results will be compared with the traditional hysteroscopic pathological findings to determine the sensitivity and specificity of these methods for early detection of endometrial cancer, thereby evaluating their potential application in early screening. Primary Objectives： 1. To evaluate the sensitivity, specificity, and accuracy of endometrial cytology for screening endometrial cancer. 2. To assess the sensitivity, specificity, and accuracy of methylation testing for screening endometrial cancer. 3. To perform further molecular testing on tissue samples obtained from endometrial cytology and cervical methylation tests, aiming to explore early screening-sensitive indicators. Secondary Objectives： 1. To determine the value of endometrial cytology in evaluating the efficacy of fertility-sparing treatments for endometrial cancer. 2. To assess the value of methylation testing in evaluating the efficacy of fertility-sparing treatments for endometrial cancer.

French Assessment of MRD by Liquid Biopsies in Colorectal With Liver Metastasis Patients (FRENCH.MRD.CRLM)

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for colorectal cancer, the methods used to decide who gets additional post-surgery treatment are suboptimal. Some patients get too much treatment, while others do not get enough. There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment after surgery. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points. The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient. FRENCH.MRD.CRLM is the French study and part of the european GUIDE.MRD project.

Observational Study of Viral BIOmarkers and microRNAs in Tumors Orofarynx and Occult Tumors Positive for Papilloma Virus

Based on the evidence summarized in the introduction, the clinician hypothesize that the detection of the presence and expression of HPV-DNA, certain miRNAs, and a certain mutational profile in the tissues and biological fluids of these patients, may have important prognostic and diagnostic value not only in HPV-related OPSCCs but also in HPV+ occult T. Accordingly, this study aims to aim to better characterize their potential as biomarkers and to detect the possibility of their their use to implement the sensitivity and specificity of radiological methodologies (PET-CT and MRI), already in use in clinical practice, for monitoring disease progression in this specific subgroup. Finally, by using the collected material to generate organoids and Patient Derived Xenograft (PDX), the study also aims to identify possible new molecular drugs, which could solve the problem of resistance to radiochemotherapy.

The Jinling Cohort

The Jinling Cohort is a prospective, multicenter cohort study in which 15,000 eligible individuals aged 45-75 in Nanjing China will be enrolled.

ProSpecTive sAmpling in dRiver muTation Pulmonary Oncology Patients on Tyrosine Kinase Inhibitors (START-TKI)

The study is perfomed with adult patients with non-small cell lung cancer treated with tyrosine kinase inhibitor. The objective is to collect repeated samples of blood from patients (starting) on a tyrosine kinase inhibitor, for liquid mutation testing, and pharmacokinetic analysis.