Goes

Researchers are evaluating the effect of PKN605, an oral medication, on atrial fibrillation, a condition affecting heart rhythm. This Phase 2 study is designed as a randomized, double-blind, placebo-controlled trial to assess how well PKN605 reduces the time participants spend in atrial fibrillation, as well as its safety, tolerability, and how the body processes the drug. The study is sponsored by Novartis Pharmaceuticals and aims to provide detailed information about the treatments impact on this heart condition. Participants will first undergo a screening period of up to 90 days to confirm eligibility. Those who qualify will be randomly assigned to receive one of two doses of PKN605 or a matching placebo. The treatment phase lasts 24 weeks, during which participants take the oral study drug and attend clinic visits about once a month. Their heart rhythm will be monitored using ECG devices throughout the study. After completing treatment, participants will have a final safety follow-up visit approximately one month later. During the study, participants will have regular ECG monitoring to measure atrial fibrillation burden and check for recurrence. Additional assessments include pharmacokinetic sampling to measure drug concentration at specific times after dosing. Researchers will evaluate the primary outcome of atrial fibrillation burden over 24 weeks and secondary outcomes related to recurrence and drug levels. Safety and tolerability are closely monitored, and participants usual heart care continues alongside study participation.

Researchers are evaluating a shorter treatment duration with androgen receptor pathway inhibitors ARPIs, specifically Apalutamide or Enzalutamide, in patients with low-volume hormone-sensitive metastatic prostate cancer. This phase 3 clinical trial aims to determine if stopping ARPI therapy after 12 months, with the option to restart if the cancer progresses, is not worse than continuing ARPI treatment. The goal is to reduce side effects and costs while maintaining effective disease control. Participants will be randomly assigned after completing 12 months of ARPI treatment to one of two groups one group will continue androgen deprivation therapy ADT combined with ARPI, while the other will stop ARPI after 12 months but may restart it if a confirmed rise in prostate-specific antigen PSA occurs. The PSA confirmation sample must be taken at least four weeks after the initial rise. Treatment will be monitored closely according to these protocols. During the study, participants will be followed for up to 6 years, including 5 years after randomization to track clinical progression-free survival. Researchers will regularly assess disease status, treatment effects, and possible side effects. The study includes regular visits and monitoring to evaluate how long patients remain free from disease progression while comparing the two treatment approaches.

Researchers are studying patients with non-metastatic stage II colon cancer who are part of the Dutch ColoRectal Cancer cohort PLCRC and who consented to additional blood samples. The study aims to evaluate how many patients with detectable circulating tumor DNA ctDNA after surgery begin adjuvant chemotherapy. This observational and interventional trial includes patients who do not have a standard indication for chemotherapy and involves a randomized design to compare ctDNA-guided treatment with standard care. Patients are randomly assigned to one of two groups the ctDNA-based treatment group or the standard care group. In the ctDNA group, blood samples taken after surgery are analyzed for ctDNA. Those with detectable ctDNA are offered 3 months of adjuvant chemotherapy using CAPOX a combination of fluoropyrimidine and oxaliplatin. Patients without detectable ctDNA receive routine follow-up care. The standard care group receives routine follow-up without knowledge of their ctDNA results. Participants will have blood collected before surgery, after surgery, and during follow-up. Researchers will monitor who starts chemotherapy within 8 to 12 weeks after surgery and will track recurrence rates, disease-free survival, overall survival, time to recurrence, quality of life, and cost-effectiveness over several years. Follow-up assessments occur up to 10 years, allowing detailed long-term evaluation of treatment impact and patient outcomes.

Researchers are studying patients with metastatic breast cancer who experience oligoprogression during palliative treatment that can be treated locally. This phase 2 study focuses on evaluating local ablative therapies such as surgery, stereotactic ablative radiotherapy SABR, and radiofrequency ablation RFA to treat progressing lesions while continuing systemic therapy. The aim is to understand how these local treatments affect disease progression and patient outcomes. The local ablative therapy will target one or two progressing metastatic lesions, which may be located in one organ, the primary tumor, or locoregional lymph nodes. Treatment options include surgery, radiotherapy, or radiofrequency ablation, chosen based on the lesions location and standard care decisions by the treating medical team. Systemic therapy with endocrine, targeted, chemotherapy, or immune-checkpoint blockade will be ongoing for at least six months before and during this local treatment. Participants will be monitored for disease progression, with the primary outcome measuring the number of patients free from progression at 6 months. Evaluations include imaging scans, such as FDG-PET-CT, to confirm oligoprogression and assess treatment response. Secondary outcomes include progression by breast cancer subtype, overall survival up to 120 months, time to next treatment, and complications after local ablative therapy. The study involves informed consent, regular follow-ups, and safety monitoring throughout the trial period.

Researchers are studying whether adjuvant chemotherapy can prevent disease recurrence in adults with high-risk rectal cancer who have detectable circulating tumor DNA ctDNA after surgery. The study aims to determine if this chemotherapy improves disease-free survival compared to standard care. Rectal cancer remains a significant cause of mortality, and while current treatments reduce local recurrence, distant recurrence rates stay high. Identifying patients with residual disease through ctDNA may help target those who might benefit from additional chemotherapy. Participants with detectable ctDNA after surgery will be randomly assigned to receive either standard care or adjuvant chemotherapy consisting of 6 cycles of FOLFOX 5FUfolinic acid and oxaliplatin every 2 weeks or 4 cycles of CAPOX capecitabine and oxaliplatin within 8 to 12 weeks after surgery. The chemotherapy treatment lasts about 3 months. The study is conducted within a prospective colorectal cancer cohort using a randomized controlled design. During the study, participants will have blood samples taken and visits with their physicians before each chemotherapy cycle if assigned to treatment. Researchers will monitor disease-free survival, overall survival, and quality of life using questionnaires over several years. They will also assess the clearance of ctDNA after chemotherapy and study its presence at recurrence. The total follow-up includes up to 2 years for disease recurrence and up to 5 years for survival outcomes.

Researchers are evaluating chemotherapy dosing strategies in older patients aged 70 years and above who have metastatic colorectal cancer and are eligible for first-line palliative chemotherapy. This phase III randomized controlled trial aims to compare upfront dose-reduced chemotherapy with standard full-dose chemotherapy, focusing on progression-free survival PFS. Patients are assessed using the Geriatric 8 G8 questionnaire to determine their risk of chemotherapy toxicity, which guides treatment assignment. The study seeks to balance treatment effectiveness with minimizing toxicity, hospital admissions, and maintaining quality of life QoL and physical functioning. Participants classified as low risk for toxicity G8 score 15 or higher are randomized to receive either doublet chemotherapy a fluoropyrimidine combined with oxaliplatin at full dose or with a 25% dose reduction upfront. Those at high risk G8 score 14 or lower or judged high risk by their oncologist receive fluoropyrimidine monotherapy either at full dose or with a 25% dose reduction. The study also allows the addition of targeted treatments like bevacizumab or EGFR inhibitors. Dose adjustments are made for patients with moderate kidney impairment. Chemotherapy is given orally or intravenously on schedules varying between every two and three weeks, depending on the regimen. Participants will be closely monitored throughout treatment, with assessments including radiological or clinical evaluations for disease progression, quality of life and physical functioning questionnaires at 1, 3, 6, and 12 months, and tracking of chemotherapy toxicity, overall survival, treatment cycles, dose changes, hospital admissions, and cumulative drug dosage. Safety and cost-effectiveness will also be evaluated over an average study duration of eight months and up to one year for some outcomes. The study plans to include 587 patients and will continue until December 2028.

Researchers are evaluating the effects of vicadrostat combined with empagliflozin in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. The study aims to assess whether this combination can help reduce cardiovascular risks compared to a placebo with empagliflozin. This Phase III trial involves adults with these conditions who are already receiving treatment for them. Participants are randomly assigned to one of two groups. One group takes vicadrostat and empagliflozin tablets daily, while the other group takes placebo tablets that look like vicadrostat but have no active medicine, alongside empagliflozin. Treatment lasts from two and a half years up to four years and three months. All participants continue their usual medications for diabetes, blood pressure, and heart disease during the study. Throughout the study, lasting up to four years and three months, participants visit the study site regularly for health checks and blood samples. Doctors monitor cardiovascular events and any side effects experienced. The main outcome measured is the time until the first cardiovascular death or heart failure event. Other health indicators like blood pressure and kidney function are also tracked to understand the effects of the treatment combination.

Researchers are investigating whether taking breaks from the standard combination therapy of daratumumab, lenalidomide, and dexamethasone Dara-Rd for newly diagnosed multiple myeloma patients affects survival and quality of life. This study aims to compare continuous treatment versus planned treatment-free intervals to see if stopping therapy temporarily may reduce side effects, allow recovery from toxicity, and improve overall well-being while controlling the disease. Participants who have completed 12 cycles of Dara-Rd with at least a partial response and no signs of disease progression will be randomly assigned to one of two groups. One group will continue Dara-Rd therapy without interruption until disease progression, while the other group will stop treatment temporarily and restart it at biochemical progression, continuing until disease progression. The trial is open-label and will follow patients for several years to assess outcomes. Throughout the study, researchers will monitor participants event-free survival and progression-free survival for up to about 57 and 69 months, respectively. Additional assessments include side effect burden, patient-reported quality of life, treatment costs, treatment-free interval length, response times, and survival after second-line therapy. Regular evaluations will help determine how treatment interruption affects toxicity, dose intensity, and overall treatment outcomes over the long term.

Researchers are evaluating the benefits and costs of routine follow-up appointments after total hip or knee replacement surgery, particularly focusing on the 1-year follow-up visit. Current guidelines recommend follow-ups with X-rays at 3 months, 1 year, and then every 5 years for knee or hip replacements. However, these frequent visits may require significant time and resources from patients, caregivers, and healthcare providers, and it is unclear if all scheduled visits are necessary. The HAKA trial aims to safely reduce these routine follow-ups and update clinical guidelines accordingly. The trial compares two approaches one group receives standard care with X-rays and clinical visits at 3 months and 1 year after surgery, while the other group has the same 3-month visit but only a 1-year visit if requested by the patient or healthcare provider. This randomized study is part of a larger research program including long-term follow-up and qualitative studies about patient and provider experiences. Participants receive care following these schedules and are monitored over time. Participants will complete questionnaires assessing physical function, pain, and quality of life before surgery and at several intervals up to 24 months after surgery. Researchers will track the number of clinical visits, X-rays, complications, additional surgeries, and related costs during this period. The study monitors outcomes to evaluate whether reducing routine follow-ups is safe and cost-effective. Overall participation lasts about two years, with regular assessments to guide care decisions.

Researchers are comparing robot-assisted radical prostatectomy RARP and external beam radiotherapy EBRT, sometimes combined with androgen deprivation therapy ADT, for men with high-risk non-metastatic prostate cancer. The study aims to understand differences in quality of life, functional outcomes, cost-effectiveness, progression-free survival, and distant metastasis-free survival. There is currently no clear consensus on which treatment is better, leading to variation in hospital practices. Participants will receive either RARP, which may include pelvic lymph node dissection and possibly adjuvant radiotherapy or androgen deprivation therapy, or EBRT delivered at an effective radiation dose, possibly combined with a brachytherapy boost and pelvic lymph node dissection. Positive lymph node findings will not exclude participants and may be treated with lymph node irradiation. Treatment details vary based on clinical decisions. During the study, participants will be followed for up to five years, with key assessments at three years including health-related quality of life and functional outcomes. Cost-effectiveness will also be evaluated at three years, while progression-free and distant metastasis-free survival will be tracked up to five years. The study involves regular monitoring to gather these outcomes and support shared decision-making for future patients.