Nijmegen

Researchers are evaluating a "wait-and-see" approach for patients with rectal cancer who respond completely to neoadjuvant chemoradiotherapy. This study aims to provide both short-term and long-term data on cancer control and patient function when surgery is avoided in good responders. The research also seeks to establish a national network of expert centers to improve organ-preserving care and create a registry to gather more evidence about this treatment strategy. The standard treatment for locally advanced rectal cancer typically involves chemoradiotherapy followed by surgery. In this study, patients who show a complete clinical response after treatment will be observed without immediate surgery under a "wait-and-see" policy. The study is a multicenter prospective observational cohort and implementation study, focusing on patients aged 18 or older who have had a long course of chemoradiotherapy or a short course with a long waiting interval. The main goal is to track disease-free survival without tumor regrowth over two years. Participants will be closely monitored using clinical exams, endoscopy, and advanced MRI scans to confirm their response and detect any regrowth early. Researchers will measure outcomes such as two-year disease-free survival, regrowth rate, local control, overall survival, quality of life, and the ability of centers to provide high-quality organ preservation care. Patients will undergo intensive follow-up to ensure safety and gather comprehensive data on the effects of this less invasive approach over time.

Carcinoma of unknown primary origin (CUP) refers to a group of cancers where metastatic disease is present, but the original tumor is not found despite thorough diagnostic tests. This condition limits treatment options since the primary tumor, which guides therapy decisions, remains unidentified. The study aims to use a new PET-CT scan with a radiotracer called [18F]F-fluoro fibroblast activation protein inhibitor (F-FAPI) to detect the primary tumor in CUP patients. This is a prospective clinical study involving 50 patients aged 18 years and older who have already undergone standard diagnostic work-up including FDG PET-CT without identifying the primary tumor. Participants will undergo a one-time [18F]F-FAPI PET-CT scan at one of six study centers. The images will be centrally reviewed, and results along with recommendations for further tests or treatment will be shared with the treating physician. After six months, the PET-CT findings will be compared with patient follow-up data including clinical, radiological, and pathological outcomes. These results will be discussed in a multidisciplinary meeting to evaluate the clinical usefulness of the [18F]F-FAPI PET-CT scan for CUP patients. During the study, patients will have only this single PET-CT examination with [18F]F-FAPI. Researchers will monitor the detection rate of the primary tumor over two years. The main outcome measured is whether the primary tumor is identified by the scan. Safety and any impact on patient care will also be assessed through follow-up and clinical evaluations. The total duration of patient involvement includes the initial scan and a six-month follow-up for outcome comparison.

Researchers are studying the natural progression of SELENON-related myopathy (SELENON-RM) and LAMA2-related muscular dystrophy (LAMA2-MD), which are rare, inherited muscle disorders causing gradual muscle weakness, spinal stiffness, scoliosis, and breathing difficulties. Currently, no cure exists, but promising preclinical treatments are being developed, with clinical trials expected to begin within five years. To support future trials and clinical care, this extended study builds on earlier data collected over 1.5 years to provide a detailed clinical description of Dutch and Flemish patients with these conditions. This is a long-term observational study involving no medical interventions. Patients will be invited to attend two follow-up visits at 3 and 5 years after their initial participation in the LAST STRONG Study. During these visits, a variety of assessments will be conducted based on age and abilities, including neurological exams, functional tests, questionnaires, muscle ultrasound and MRI scans, lung function tests, and activity monitoring using accelerometers. Participants will undergo evaluations to measure their motor function and overall health status over time. These include standard medical history reviews, physical examinations, imaging, and questionnaires. Data on motor function changes will be collected at 3 and 5 years to better understand disease progression. The study poses minimal risk and offers participants a chance to learn about their own health while helping to prepare for future clinical trials.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd) alone or combined with other treatments in people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to understand how well patients tolerate the treatment, find a safe dose for combining I-DXd with other drugs, and measure prostate-specific antigen (PSA) levels during treatment. The study is part of a larger master screening protocol and includes patients with confirmed prostate adenocarcinoma who have progressive disease despite prior therapies. Participants receive treatments including I-DXd given through intravenous infusion, sometimes combined with other drugs such as docetaxel (IV), MK-5684, abiraterone, or enzalutamide (all oral). Before each I-DXd dose, patients take premedication to prevent nausea and vomiting. The study includes both a safety lead-in phase and an efficacy phase, with ongoing monitoring for side effects and tolerability. The combination therapies are carefully dosed and scheduled according to the study protocol. During the study, participants undergo regular assessments to monitor side effects, measure PSA response, and track any dose-limiting toxicities. Safety is closely followed, particularly during the first 21 days for combination treatments, and throughout up to 54 months for long-term outcomes. Researchers also observe if participants discontinue treatment due to adverse events. The study requires ongoing visits and evaluations to ensure participant health and collect data on treatment effects over time.

Researchers are evaluating MK-8294, a targeted therapy designed to treat various advanced solid tumors, including head and neck squamous cell carcinoma, cervical squamous cell carcinoma, esophageal squamous cell carcinoma, triple-negative breast cancer, estrogen receptor/progesterone receptor positive, HER2-negative breast cancer, endometrial, and bladder cancer. This phase 1 open-label study aims to assess the safety of MK-8294, determine how well participants can tolerate it, and identify the highest dose that can be safely administered. The study includes participants who have previously failed standard treatments, lack standard treatment options, or cannot tolerate standard therapy. Participants receive MK-8294 through intravenous infusions at increasing doses ranging from 30 micrograms to 70 milligrams. The study involves monitoring participants for dose-limiting toxicities and adverse events over the course of treatment, which may last up to approximately two years. Additionally, a CD8 PET tracer is administered via IV infusion as part of the study procedures. During their participation, individuals will undergo regular safety assessments, including monitoring for adverse events and treatment tolerability. Researchers will track any dose-limiting toxicities within about 35 days and continue to observe adverse events and reasons for discontinuation for up to two years. The study involves various evaluations such as laboratory tests and imaging to assess safety and treatment effects throughout the study period.

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Researchers are investigating treatments for women with recurrent endometrial cancer that expresses different levels of the HER2 protein. The study has two groups based on the tumor's HER2 score: Cohort 1 includes patients with HER2 IHC 1+ or 2+ who have previously received immune checkpoint inhibitors and platinum-based chemotherapy, while Cohort 2 includes patients with HER2 IHC 3+. The purpose is to compare the effectiveness and safety of the investigational drug BNT323 (also called DB-1303) against chemotherapy in Cohort 1 and to evaluate BNT323 alone in Cohort 2. The study also looks at how the drug affects the immune system, the body's handling of the drug, quality of life, and potential side effects. Participants in Cohort 1 are randomly assigned to receive either BNT323 via intravenous infusion or a chemotherapy drug chosen by the investigator (doxorubicin, paclitaxel, or docetaxel if paclitaxel is unsuitable). Treatment continues until the cancer progresses, unacceptable side effects occur, or the participant withdraws consent. Those in Cohort 2 receive BNT323 alone until disease progression or other discontinuation criteria are met. The study includes a screening period, a treatment period expected to last about six months, followed by safety monitoring, efficacy follow-up, and long-term survival follow-up lasting up to approximately 53 months. During the study, participants undergo regular assessments including imaging scans to measure tumor response by RECIST criteria, safety monitoring for adverse effects, and evaluations of quality of life. Researchers also study the pharmacokinetics of BNT323 and the immune response. The main outcomes measured are progression-free survival in Cohort 1 and objective response rate in Cohort 2. Safety follow-up ensures ongoing monitoring after treatment to evaluate longer-term effects and participant wellbeing.

Researchers are studying the effect of the hormone therapy drug leuprorelin on liver growth in pre-menopausal women with very severe polycystic liver disease who continue to experience liver growth despite available treatments and are at risk of needing a liver transplant. This phase 2 trial focuses on women aged 18 to 45 who have large livers for their age and ongoing liver growth confirmed by MRI or CT scans. The study aims to evaluate whether leuprorelin can affect the total liver volume over 36 months. Participants are divided into two groups: one starts leuprorelin treatment immediately, and the other receives standard care for the first 18 months before beginning leuprorelin. The treatment starts with monthly injections of 3.75 mg leuprorelin for three months, followed by injections of 11.25 mg every three months. This treatment continues for a total of 36 months in the direct start group. During the study, women will undergo MRI scans to measure liver volume and track liver growth. Researchers will monitor safety and liver changes throughout the 36 months. Participants must provide informed consent and complete study questionnaires. The study also includes careful screening and follow-up to ensure participant safety and accurate measurement of treatment effects on liver volume.