Leeuwarden

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.

Researchers are evaluating the effectiveness of adding LY3537982 (olomorasib) to standard anti-cancer drugs compared to standard treatment alone in participants with untreated advanced non-small cell lung cancer (NSCLC) that has a specific KRAS G12C gene mutation. This pivotal Phase 3 trial includes participants with locally advanced or metastatic NSCLC and considers their programmed death-ligand 1 (PD-L1) expression levels. The study includes multiple parts: Dose Optimization, Part A, and Part B are randomized, while Safety Lead-In for Part B and Part C are non-randomized. Treatments being assessed include LY3537982 taken orally, pembrolizumab administered intravenously, and standard chemotherapy drugs such as cisplatin, carboplatin, and pemetrexed given intravenously. Participants receive these treatments according to their assigned groups based on their PD-L1 expression and tumor histology. Participants will be monitored with regular assessments including measuring disease progression, safety evaluations, and treatment emergent adverse events for up to approximately one year, with overall study participation potentially lasting up to three years depending on individual response and health status. Outcome measures focus on progression-free survival and safety, capturing any adverse events from the start of treatment until disease progression or death.

Researchers are evaluating the effects of the drug orforglipron compared with a placebo on cardiovascular outcomes in adults who have atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). This is a Phase 3, randomized, double-blind, placebo-controlled study designed to investigate major adverse cardiovascular events over a long period. Participants will receive either orforglipron or a placebo orally. The study is event-driven and will continue until the occurrence of major cardiovascular events or up to about 5 years. The treatments are administered without revealing to participants which group they are in to ensure unbiased results. During the study, participants will be monitored for the time to the first occurrence of a major cardiovascular event. Researchers will collect data from baseline through the end of the study, which lasts approximately 5 years. Regular assessments will help evaluate the safety and effects of the treatments on cardiovascular health in this population.

Researchers are evaluating whether adding intismeran autogene to pembrolizumab after surgery can help people with non-small cell lung cancer (NSCLC) remain cancer-free longer compared to pembrolizumab with a placebo. This study focuses on patients with NSCLC whose tumors did not completely respond to treatment before surgery and aims to prevent the cancer from returning. It is a Phase 3 randomized, double-blind study involving participants with resectable Stage II to IIIB (N2) NSCLC. Participants receive treatments including pembrolizumab given as an intravenous infusion and either intismeran autogene or placebo administered as an intramuscular injection. Before surgery, patients have received neoadjuvant pembrolizumab combined with platinum-based doublet chemotherapy, but only those who did not achieve a complete pathological response are eligible. The study compares the effects of pembrolizumab with or without intismeran autogene following surgery. During the study, participants are closely monitored for disease-free survival over a period of up to approximately 97 months. Researchers will assess whether the cancer returns and evaluate overall safety. Participants undergo regular evaluations including clinical assessments and laboratory tests to monitor their health and treatment response throughout the study period.

Researchers are evaluating zolbetuximab combined with pembrolizumab and chemotherapy in adults with locally advanced, unresectable, or metastatic stomach or gastroesophageal junction (GEJ) cancer. This study focuses on cancer cells that are HER2-negative but positive for the Claudin 18.2 protein and PD-L1, exploring how well zolbetuximab helps the immune system attack the tumor alongside immunotherapy and chemotherapy. The trial is a phase 3, randomized, double-blind study designed to compare the overall survival of participants receiving zolbetuximab with pembrolizumab and chemotherapy versus those receiving a placebo with pembrolizumab and chemotherapy. Participants receive study treatment in 6-week cycles, with zolbetuximab or placebo given by infusion every 2 or 3 weeks. Chemotherapy regimens include either CAPOX (capecitabine tablets and oxaliplatin infusion) or mFOLFOX6 (infusions of 5-fluorouracil, folinic acid, and oxaliplatin) administered on schedules matching the cycles. Pembrolizumab is infused every 3 or 6 weeks. Treatment continues until cancer worsens, is not tolerated, or another therapy is needed, with pembrolizumab given for up to 2 years. After initial cycles, some chemotherapy drugs are adjusted to only include oral capecitabine or certain infusions. During the study, participants visit the clinic for treatments, health checks, and scans to monitor cancer changes and side effects. Researchers also track medical problems related to the treatments and may collect tumor samples if cancer worsens. After stopping treatment, participants have follow-up visits and scans every 9 to 12 weeks, along with telephone check-ins every 3 months. The primary outcome measured is overall survival up to 72 months, with ongoing monitoring to evaluate safety and treatment effects.

Researchers are evaluating the combination of the investigational drug PF-06821497 (mevrometostat) with enzalutamide compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC) who have not previously received androgen receptor signaling inhibitors (ARSi) or abiraterone. This global, multicenter Phase 3 study focuses on participants whose cancer has progressed despite androgen deprivation therapy (ADT) or first-generation anti-androgens but who have not started other systemic anti-cancer treatments for mCRPC. The study excludes those with prior treatment using enzalutamide, darolutamide, apalutamide, or abiraterone in any setting, though chemotherapy is allowed in the hormone-sensitive setting. The study includes a Screening Phase, followed by randomization where participants are assigned equally to one of two groups: one receiving PF-06821497 plus enzalutamide, and the other receiving placebo plus enzalutamide. All treatments are taken orally on a continuous basis. After the treatment phase, participants enter a Safety Follow-up and a Long-Term Follow-up period to monitor ongoing effects. Participants will undergo assessments during the study to evaluate radiographic progression-free survival over about three years. Researchers will collect imaging data such as bone scans and CT or MRI scans to monitor disease progression. Additional evaluations include performance status, life expectancy assessments, and safety monitoring for adverse events. The study duration spans from screening through treatment and follow-up phases to gather comprehensive data on the combination therapy's impact on mCRPC.

Researchers are studying the effects of CIT-013, a drug being evaluated for treating adults with moderately active rheumatoid arthritis (RA). This Phase IIa clinical trial aims to determine if CIT-013 reduces disease activity in RA patients and to assess the safety of the drug. The study compares three different doses of CIT-013 to a placebo to see if it improves symptoms and lowers disease activity scores in participants. Participants will receive subcutaneous injections of either low, medium, or high doses of CIT-013 or a placebo every other week for 6 weeks. The study is double-blinded and randomized, meaning neither participants nor researchers know who receives which treatment until the study is complete. Treatment is administered in a controlled manner to evaluate the effect of different dose levels on RA symptoms. During the study, participants will visit the clinic every 2 weeks for checkups and tests. Researchers will monitor disease activity using the DAS28-CRP score at week 6 compared to baseline. Participants will also be monitored for any medical problems or side effects while receiving treatment. This helps researchers understand how well CIT-013 works and its safety profile over the 6-week treatment period.

Researchers are investigating a treatment approach for older adults with acute myeloid leukemia (AML) who are not fit for intensive chemotherapy. The study focuses on combining venetoclax with hypomethylating agents (HMAs) like azacitidine, which have milder side effects suitable for older or medically fragile patients. The addition of cobicistat, a CYP3A4 inhibitor, aims to boost venetoclax exposure, potentially reducing the venetoclax dose and lowering treatment costs while maintaining effectiveness. This is a Phase II trial targeting newly diagnosed AML patients who are unable or unwilling to undergo intensive chemotherapy. Participants will receive azacitidine and venetoclax starting at Cycle 1 and continuing until disease relapse. Cobicistat will be introduced from Cycle 2 during the run-in phase and from Cycle 1 in the extension phase, continuing until relapse. This design evaluates the pharmacokinetic equivalence of cobicistat-boosted venetoclax compared to unboosted venetoclax and monitors overall survival up to 48 months. The trial is single-arm, assessing the combined treatment's safety and effectiveness in the specified patient group. During the study, patients will undergo regular monitoring including pharmacokinetic assessments in early cycles and survival follow-up for up to four years. Researchers will evaluate venetoclax blood levels, overall survival, and treatment safety. Participants must provide informed consent and agree to contraception measures if applicable. The trial excludes patients with certain medical conditions or prior treatments that could interfere with the study. This careful follow-up ensures comprehensive evaluation of treatment impact and patient health throughout the trial.

Researchers are evaluating the use of Autologous Fat Transfer (AFT) with pre-expansion as a full breast reconstruction method for female breast cancer patients who have undergone or will undergo mastectomy. This multicenter prospective cohort study aims to monitor the quality of life, aesthetic outcomes, complications, oncological safety, and cost-effectiveness of AFT. The study builds on the previous BREAST trial that compared AFT with implant-based reconstruction, but here all patients receive AFT. Participants in this study will undergo full breast reconstruction using AFT combined with an external expansion device. This procedure is offered to women who have had or are candidates for mastectomy, including those undergoing preventive mastectomy. The external expansion device must be worn by participants to assist the reconstruction process. There is no comparator group in this study as all patients receive the AFT treatment. During the study, participants will be followed for at least two years to evaluate breast-related quality of life and other outcomes. Researchers will monitor safety, aesthetic results, and complications throughout this period. Patients will be assessed regularly to track their progress and any adverse effects related to the treatment, with particular attention to oncological safety and overall well-being after reconstruction.

Researchers are evaluating the effects of combining two chemotherapy drugs followed by immunostimulants on the immune response within tumors in patients with newly diagnosed metastatic or locally advanced esophagogastric cancer. This Phase 2, multi-center, open-label study focuses on assessing interferon gamma expression and the infiltration of cytotoxic T cells in the tumor environment of patients with mismatch repair-deficient (dMMR) esophagogastric cancer. Participants receive two cycles of chemotherapy with capecitabine and oxaliplatin (CapOx), each cycle lasting three weeks. After chemotherapy, patients are treated with intravenous retifanlimab, an immunotherapy drug, given every four weeks for up to two years. The study plans to enroll 25 patients. During treatment, tissue biopsies, blood, and fecal samples are collected to study immune cells and interferon gamma levels. CT scans are performed before and after chemotherapy and after two to three cycles of immunotherapy to evaluate tumor response. Participants are involved in regular assessments including biopsies, imaging scans, and laboratory tests to monitor immune response and tumor status. Researchers track the effects of the treatments on immune cell infiltration and interferon gamma expression within tumors over 40 months. The study also monitors safety and treatment adherence throughout the treatment period and follow-up.