Clinical Research Directory

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)

Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn: * About the safety of MK-1084 and if people tolerate it when taken with other treatments * How many people have the cancer respond (get smaller or go away) to the treatments

Confocal Laser Endomicroscopy VERification

The goal of this multi-center randomized clinical trial is to evaluate the added value of needle based confocal laser endomicroscopy (nCLE)-imaging to regular diagnostic bronchoscopic peripheral lung lesion analysis on the diagnostic yield in patients with peripheral pulmonary nodules suspect for malignancy. The main question\[s\] it aims to answer are: To determine if the addition of nCLE-imaging to conventional diagnostic bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure). Participants will undergo diagnostic bronchoscopy either with or without the addition of nCLE imaging before each TBNA. Based on the feedback of the CLE images on (in)correct placement of the needle, the needle might be repositioned before sampling. Comparison between the diagnostic yield of these groups will be done including subgroup analysis.

Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01)

The main goals are after treatment given before surgery, to measure the number of people who have no signs of cancer cells in tumors and lymph nodes removed during surgery; and to learn about whether the cancer gets smaller or goes away by measuring the number of people with a certain number of living cancer cells in the tumor removed during surgery.

Benefit of Spectral Information in Patients Suspected for Lung Cancer

Purpose The aim of the study is to investigate the utilization of photon counting CT (PCCT) and the spectral information provided to determine the impact of spectral information on follow-up examinations. As secondary aims we will compare conventional CT, CT + 18Flouro-deoxy-glucose (18F-FDG) positron emission tomography (PET) and PCCT + 18F-FDG PET for the tumor-node-metastasis (TNM) staging of lung cancer patients. PCCT with and without spectral information to assess the need for additional work-up,TNM classification, and sensitivity/specificity for malignant lesions. Patients will be randomized for reading with or without spectral information available within a clinical setting. The clinical readings are performed as a structured reports of all significant findings. Including both malignant and benign findings. Furthermore, in case additional follow-up/work-up is needed based on the guidelines on incidental findings by the American College of Radiology (ACR), this will be reported as well. If lesions suspicious of pulmonary malignancy is present, a provisional TNM classification is provided based on the scan findings. After 3 months, the patient record is reviewed where additional examinations that can be attributed to the PCCT scan are recorded. The financial impact is calculated by a health economist based on the findings. PET/CT, conventional CT and PCCT combined with PET will be assessed retrospectively for comparison. Endpoints are number of supplementary examinations and cost savings. Sensitivity and specificity for any malignant finding. The T, N and M stages are assessed separately as diagnostic measures by the McNemar's test with a reference standard from the Danish Lung cancer register. The number of malignant lesions will be determined by reviewing the patient records incl. pathology assessment if available 12 months after inclusion of the last patient.

Intestinal Low Dose Radiotherapy Combined With Immunotherapy in Immune-resistant Metastatic Malignant Solid Tumors

Preclinical and clinical evidence suggests that intestinal low-dose radiotherapy (ILDR) may enhance antitumor immune responses by modulating the gut microenvironment, thereby improving the efficacy of immune checkpoint inhibitors (ICBs) in refractory solid tumors. Based on these findings, the investigators initiate a multicohort phase II clinical trial to evaluate the clinical benefit and safety of ILDR combined with PD-1/PD-L1 monoclonal antibody therapy in patients with metastatic solid tumors resistant to prior ICB treatment. In this study, patients are stratified into three parallel cohorts by tumor type (lung cancer, esophageal cancer, and other solid tumors), with 16 patients per cohort (48 in total, including subjects enrolled from the ILDR-01 study). Eligible participants includes patients with advanced metastatic solid tumors progressing after monotherapy or combination ICB treatment, meeting criteria of ECOG performance status 0-2, life expectancy ≥3 months, and have at least one measurable lesion. Exclusion criteria encompasses prior pelvic radiotherapy, ongoing infections, major organ dysfunction, or concurrent antitumor therapies. The primary endpoints includes objective response rate (ORR), disease control rate (DCR), progression-free survival after ILDR (PFS2), and the incidence of abscopal effects. Secondary endpoints includes overall survival (OS), treatment safety, α/β diversity changes in gut microbiota, peripheral blood immune cell subset dynamics, and tumor immune microenvironment remodeling characteristics. All patients receives a 1 Gy jejunoileal radiotherapy followed by PD-1/PD-L1 monoclonal antibody administration (in accordance to prior protocols or guidelines) within 24 hours, with maintenance therapy up to 2 years. Therapeutic efficacy is assessed via RECIST v1.1, while therapeutic toxicity is assessed according to CTCAE v5.0. Paired pre- and post-treatment samples (including wumor tissue, stool, peripheral blood etc.) are collected for metagenomic sequencing, metabolomic analysis, and multi-omics integrative modeling to systematically elucidate the regulation mechanism of gut microbiota-metabolite-immune axis mediated by ILDR. This approach aims to provide theoretical foundations for optimizing treatment strategies in immunotherapy-resistant tumors and identify biomarkers that potentially associated with therapeutic efficacy.

Preoperative Sintilimab Combined With Bevacizumab and Chemotherapy for Resectable Non-Small Cell Lung Cancer

Neoadjuvant chemotherapy followed by surgery has been recommended as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. Drugs targeting PD-1/PD-L1 pathway have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents targeting VEGF (bevacizumab) has also been used for the first line treatment of advanced or metastatic NSCLC. Therefore, we conduct this single-arm clinical trial, which aims to investigate the safety and feasibility of neoadjuvant sintilimab combined with bevacizumab and chemotherapy followed by surgery in treating locally advanced and resectable NSCLC.

MONDRIAN: Multi-omics Integrative Modelling for Stereotactic Body Radiotherapy in Early-stage Non-small Cell Lung Cancer

Stereotactic Body Radiotherapy (SBRT) is a form of high-precision radiotherapy playing a major role in patients diagnosed with early-stage non-small cell lung cancer (NSLCL), especially when surgery cannot be performed. It is a non-invasive, well-tolerated treatment, with an excellent ability to control disease recurrence. However, in some patients, disease response is suboptimal: understanding why this happens may open doors to more aggressive approaches, such as the combination with systemic therapies. Hence, the goal of this observational trial is to understand which clinical, imaging, and biological factors are associated with response to SBRT through the development of complex models. In other words, the main question it aims to answer is: "Will this patient respond to radiation treatment based on the characteristics of their disease?". Participants will be treated according to the best clinical practice standards, in agreement with international, national, and internal guidelines. Researchers will compare data collected from patients treated with SBRT with those collected from a similar group of patients, who will be treated with surgery, to see which factors are actual predictors of response to SBRT, or rather are indicators of more or less aggressive disease behavior.

Broadband Collaborative Pulse Ablation Instrument Treating Malignant Pulmonary Nodules

Effectiveness safety and feasibility of the broadband collaborative pulse ablation instrument in treating malignant pulmonary nodules