Nijmegen

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Carcinoma of unknown primary origin CUP is a group of cancers where metastatic disease is present but the original tumor cannot be found despite extensive tests. This condition limits treatment options since therapies often target known primary tumors. Researchers are evaluating whether a new imaging test called 18FF-fluoro fibroblast activation protein inhibitor F-FAPI PET-CT can detect the primary tumor in patients diagnosed with CUP after standard diagnostic scans including FDG PET-CT. This multi-center, prospective clinical study involves 50 adult patients with CUP to better understand the usefulness of this new scan method. Each participant will undergo a single 18FF-FAPI PET-CT scan at one of the six study centers. Images from this scan will be centrally reviewed and shared with the treating doctor, who may recommend further tests or treatments based on the findings. After six months, results from the F-FAPI PET-CT will be compared with clinical, radiological, and pathological follow-up data. A multidisciplinary panel will then review all information to decide how valuable the 18FF-FAPI PET-CT is for identifying the primary tumor in CUP patients. Participants will be involved in one main scanning visit and followed for six months through routine clinical assessments. The study team will monitor detection of the primary tumor using the new scan as the main outcome, and also assess the tests accuracy measures like sensitivity and specificity. Participation requires being able to undergo the scan and complete follow-up, with the entire process lasting about two years for outcome measurement. This study is sponsored by Erasmus Medical Center.

Researchers are evaluating the use of 68GaBED003, a diagnostic imaging agent, in detecting multiple types of cancer including colorectal, gastric, pancreatic ductal adenocarcinoma, invasive lobular breast carcinoma, and epithelial ovarian cancer. This Phase 2, open-label, single-arm study aims to assess how well 68GaBED003 performs in identifying these cancers through imaging techniques. Each participant will receive an injection of 68GaBED003 followed by positron emission tomography PETcomputed tomography CT scans during the imaging visit. The study includes a screening period, the imaging procedure, and a brief safety follow-up. The main focus is on the diagnostic accuracy of 68GaBED003, including tumor uptake and optimal imaging timing and dosage. Participants will undergo screening to confirm eligibility, including performance status and pregnancy testing for women of childbearing potential. They will receive the imaging agent and have PETCT scans at the imaging visit. Safety and tolerability are monitored up to 48 hours after injection, with follow-up assessments up to 42 days. The study measures how well 68GaBED003 detects cancer in the peritoneum and other sites, with the entire participation lasting a few weeks around the imaging and follow-up visits.

Researchers are studying SELENON-related myopathy SELENON-RM and LAMA2-related muscular dystrophy LAMA2-MD, which are rare neuromuscular disorders characterized by progressive muscle weakness, spinal rigidity, scoliosis, and breathing difficulties. There are currently no curative treatments, but promising preclinical research is underway. This extended study builds on previous 1.5-year data to better understand the natural history of these diseases and prepare for future clinical trials and care improvements. The study is an observational natural history study involving Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD. Participants will have two follow-up visits at 3 and 5 years after their initial visit. During these visits, they will undergo various assessments including neurological exams, functional tests, questionnaires, muscle ultrasound, MRI scans, lung function tests, and activity monitoring using accelerometers. The tests are tailored to each participants age and abilities. Participants will be carefully evaluated over time with measures such as motor function, physical activity, muscle condition, pulmonary function, pain, fatigue, and quality of life. These assessments help track changes from baseline at 3 and 5 years. The study poses minimal risk and aims to provide detailed health information to participants while supporting the development of future treatment trials. The total participation duration spans at least five years from the first visit.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

This research investigates treatments for metastatic castration-resistant prostate cancer mCRPC focusing on a drug called ifinatamab deruxtecan I-DXd. The study aims to assess the safety, how well participants tolerate the treatments, and appropriate dosing levels of I-DXd alone or combined with other therapies. Researchers will also monitor participants prostate specific antigen PSA levels during treatment to understand its effects. Participants are assigned to one of several treatment groups. One group receives docetaxel every three weeks for up to 10 cycles. Other groups receive I-DXd alone or combined with either opevesostat or androgen receptor pathway inhibitors such as abiraterone acetate or enzalutamide. I-DXd is given every three weeks until unacceptable side effects, disease progression, death, or withdrawal, while the other drugs continue until specific discontinuation criteria are met. Premedication is required before each I-DXd dose to prevent nausea and vomiting. Throughout the study, participants undergo various assessments including monitoring of dose-limiting toxicities, adverse events, and PSA response rates. Researchers also track objective response rates, progression-free survival, overall survival, and other clinical outcomes over up to approximately 54 months. The study involves regular evaluations to assess safety and treatment effects until study completion.

Researchers are studying MK-8294, a targeted therapy designed to treat advanced solid tumors, including various squamous cell carcinomas and breast, endometrial, and bladder cancers. This phase 1 open-label study aims to evaluate the safety of MK-8294, determine if patients can tolerate it, and identify the highest dose level that participants can handle. The study enrolls adults with confirmed advanced or metastatic solid tumors who have limited or no standard treatment options. Participants will receive MK-8294 as a monotherapy in escalating intravenous doses starting from 30 micrograms up to 70 milligrams, given on Days 1, 8, and 15 of each 21-day cycle. There is no maximum number of treatment cycles, and participants will continue treatment until criteria for stopping are met. Some participants may also undergo optional PET imaging using a CD8 tracer to help assess treatment effects. Throughout the study, participants will be carefully monitored for side effects and treatment tolerance, with dose-limiting toxicities tracked up to about 35 days. Researchers will also observe adverse events and reasons for discontinuing treatment for up to approximately two years. Blood samples will be collected during each cycle to measure MK-8294 levels and immune responses. The overall study duration may last up to two years to fully assess safety and treatment effects.

Researchers are studying pulmonary arterial hypertension PAH, a condition where lung blood vessels become thick and narrow, causing high blood pressure in the lungs and making it hard for the heart to work. PAH can cause difficulty breathing and limit activity. While standard treatments help symptoms, they do not stop the disease from worsening. This research focuses on sotatercept, a targeted therapy aimed at specific proteins involved in PAH, to learn about its long-term safety and tolerability when added to usual PAH treatments. Participants in this long-term follow-up study, who previously took part in certain sotatercept trials, may continue receiving sotatercept by subcutaneous injection every three weeks. Those coming from blinded studies start at 0.3 mgkg with possible increases up to 0.7 mgkg, while those from unblinded studies continue their current dose with possible titration to 0.7 mgkg. The study monitors participants over an extended period to assess continued effects alongside their usual PAH therapy. During the study, participants will have regular assessments including monitoring for adverse events, blood tests for blood components and chemistry, body weight, blood pressure, and ECG readings. Researchers will also evaluate exercise capacity, heart function markers, and risk scores related to PAH. The study aims to follow participants for up to approximately 7 to 8 years to understand long-term safety, treatment tolerability, and health changes while using sotatercept with standard PAH care.

Researchers are evaluating the effectiveness and safety of an investigational drug called BNT323 also known as DB-1303 compared with standard chemotherapy in women with recurrent endometrial cancer. The study includes two groups based on the level of HER2 protein in the tumor Cohort 1 with HER2 levels 1 or 2 who have been previously treated with immune checkpoint inhibitors, and Cohort 2 with HER2 level 3. The study aims to understand how well BNT323 or chemotherapy controls cancer progression and how the drug affects patients immune response and quality of life. Participants in Cohort 1 will be randomly assigned to receive either BNT323 or chemotherapy drugs such as doxorubicin, paclitaxel, or docetaxel. In Cohort 2, participants will receive BNT323 alone. Treatments are given intravenously and continue until the cancer progresses, unacceptable side effects occur, or consent is withdrawn. The study includes screening, treatment, safety follow-up, efficacy follow-up, and a long-term survival follow-up lasting up to about 53 months. During the study, participants will undergo regular assessments including tumor evaluations, safety monitoring, and quality of life questionnaires. Researchers will measure progression-free survival in Cohort 1 and tumor response rate in Cohort 2. Safety is monitored by tracking adverse effects and drug levels in the body. Participants can expect to be followed for up to 53 months after treatment to assess long-term outcomes and survival.