Leidschendam

Researchers are evaluating the safety and effectiveness of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as initial treatments for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC) whose tumors express PD-L1. This Phase III, randomized, double-blind, global study focuses on patients whose tumors meet the PD-L1 expression threshold of 1% or higher and do not have certain genetic mutations or rearrangements that would require other targeted therapies. Participants receive either rilvegostomig or pembrolizumab intravenously on the first day of each 21-day treatment cycle. Both groups also receive platinum-based chemotherapy drugs such as carboplatin or cisplatin, administered intravenously up to four cycles, along with pemetrexed given intravenously on Day 1 of each cycle. The study monitors these treatments as first-line therapy for metastatic non-squamous NSCLC. During the study, participants undergo regular assessments including imaging scans to measure tumor size and response, as well as evaluations of organ and bone marrow function. Researchers track overall survival and progression-free survival for up to approximately five years. Safety is closely monitored throughout, and patients are followed long-term to assess outcomes related to treatment effectiveness and tolerability.

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

Researchers are investigating the use of elacestrant compared to standard endocrine therapy in patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer who have a relapse detected by circulating tumor DNA (ctDNA). This international, multi-center, randomized, open-label phase III trial aims to determine if elacestrant offers a benefit over current endocrine treatments in this group of patients without distant metastases. The study includes a lengthy ctDNA screening phase to identify eligible participants and monitor their disease status over time. The study begins with a ctDNA screening phase, where patients receive standard adjuvant endocrine therapy such as tamoxifen, letrozole, anastrozole, or exemestane, and have blood collected every six months for ctDNA testing until about 5.7 years after enrollment ends. Those who test positive for ctDNA and show no distant metastasis on imaging will be randomized within four weeks to continue their current endocrine therapy or switch to elacestrant taken orally at 400 mg daily. Treatment duration varies based on prior endocrine therapy exposure, ranging from two to seven years. After treatment, further care is at the physician's discretion. Participants will have frequent follow-up visits with ctDNA testing at weeks 4 and 16 post-randomization and every 16 weeks thereafter for up to three years. Imaging studies including mammograms, bone scans, and CT scans will be conducted regularly to monitor for distant metastases or new cancers. The main outcome measured is distant metastasis-free survival, assessed up to 6.25 years following the first patient enrollment. The study ends when all patients complete their visits or discontinue for reasons such as withdrawal, loss to follow-up, or death, and data is fully analyzed and finalized.

Researchers are investigating the treatment of multiple myeloma using a combination of medicines called daratumumab-lenalidomide-dexamethasone (Dara-Rd). This standard treatment in the Netherlands often suppresses the disease for a long time and continues until it stops being effective. The study aims to find out if stopping treatment temporarily, compared to continuing it without breaks, can improve quality of life by reducing side effects and allowing recovery from toxicity, without reducing survival time. The study involves patients who have completed 12 cycles of Dara-Rd treatment and have responded with at least a partial response without biochemical progression. These patients will be randomly assigned to either continue Dara-Rd treatment continuously or take a treatment-free interval. The medications involved include daratumumab injections, lenalidomide capsules, and dexamethasone. Reduced dosing of lenalidomide is allowed but not below 5 mg, and prior dexamethasone dose changes are permitted. The trial is a nationwide, open-label, randomized Phase III study. Participants will be followed for up to approximately 57 months to compare event-free survival and up to 69 months to compare progression-free survival after randomization. Researchers will monitor disease status, side effects, and overall health during this time. Patients must provide informed consent and will undergo regular assessments to evaluate the impact of continuous versus interrupted therapy on their disease and quality of life.

This research evaluates a new radiotherapy approach for treating brain metastases, comparing the current standard stereotactic radiotherapy (SRT) delivered in one or three fractions to fractionated stereotactic radiotherapy (fSRT) given in five fractions. The study aims to find a potentially safer treatment method with fewer long-term side effects such as brain necrosis, which can affect up to 40% of patients depending on the tumor size and radiation dose. It is a randomized phase II trial focusing on survival, side effects, and quality of life. Participants receive either standard SRT treatment in one or three sessions or fSRT treatment spread over five sessions. The study carefully monitors both groups to compare the effects of these two radiation schedules on tumor control and brain health. Both treatments are forms of precise radiotherapy aimed at targeting brain metastases while minimizing damage to surrounding healthy tissue. During the study, participants undergo regular assessments including imaging scans and quality of life questionnaires. Researchers track the occurrence of side effects like radio necrosis and tumor recurrence over a two-year period after treatment. The study measures overall survival, toxicity, and patient-reported outcomes to evaluate the treatments. Participants are followed closely to ensure safety and to collect comprehensive data on treatment effectiveness.

Researchers are evaluating treatments for patients with locally recurrent rectal cancer in a phase III, multicenter, open-label study. The trial compares two treatment approaches: one group receives induction chemotherapy followed by chemoradiotherapy and surgery, while the other group receives chemoradiotherapy and surgery alone. The goal is to determine which treatment better supports clear removal of cancer during surgery. The experimental treatment involves induction chemotherapy using either CAPOX, FOLFOX, or FOLFIRI regimens, with cycles and dosages determined by the oncologist. Patients showing stable or responding disease may continue chemotherapy before proceeding to chemoradiotherapy. Chemoradiotherapy uses capecitabine alongside radiotherapy, with radiation doses adjusted based on prior treatments. Surgery varies depending on tumor location and involvement of nearby tissues, with optional intraoperative radiotherapy. Participants will be closely monitored for treatment effectiveness and safety, including the proportion of patients achieving clear margins after surgery. Assessments include imaging and clinical evaluations, with follow-up to observe outcomes. The study requires patients to be adults with confirmed resectable locally recurrent rectal cancer and good overall health status. Total participation time and detailed monitoring schedules are structured according to treatment phases and evaluations.

Researchers are studying breast cancer patients who have cancer that has spread to lymph nodes and are treated with neoadjuvant systemic therapy (NST), which includes chemotherapy and sometimes immunotherapy. The study focuses on how to best check and treat the lymph nodes after NST, comparing less invasive methods to the traditional axillary lymph node dissection (ALND). The goal is to see if less invasive techniques can offer similar cancer control and quality of life benefits. This multicenter observational study includes patients with positive lymph nodes who receive NST followed by breast and axillary treatment. Data on patient characteristics, tumor details, staging before and after NST, and treatments will be collected into a national database. Patients will complete quality of life questionnaires at diagnosis, and then 1 and 5 years later to understand the impact of different axillary treatment strategies. Participants will be followed for 5 years to evaluate disease-free survival, breast cancer-specific survival, overall survival, and rates of cancer returning in the lymph nodes. Quality of life will be measured using multiple questionnaires over time. The study aims to provide evidence to improve national guidelines and support shared decision-making about axillary treatment options for node positive breast cancer patients.

Researchers are evaluating a comprehensive treatment approach for men with high risk prostate cancer. This study aims to determine whether combining several recent advances in prostate cancer radiotherapy is safe, focusing on oncological outcomes and side effects. Key background includes improvements shown by previous trials in focal boosting, elective lymph node irradiation, and hypofractionation, as well as reducing androgen deprivation therapy to minimize side effects. None of these treatments have been combined before in one protocol for high risk prostate cancer. The treatment being studied is called HYPOPRIME, which involves hypo fractionated pelvic radiotherapy targeting the prostate tumor with a higher dose boost and elective lymph node irradiation. Androgen deprivation therapy is minimized as much as possible to reduce toxicity. Participants will receive this combined radiation treatment, which has been shown safe in separate studies but is now being tested together in this prospective cohort study with a contemporary matched control group. During the study, participants will be monitored for biochemical recurrence-free survival over 5 years and assessed for late gastrointestinal, genitourinary toxicity, and erectile dysfunction at 6 months and 2 years. The study involves standard clinical follow-up without extra tests or visits beyond usual care. Researchers will carefully observe the safety and side effect profile of this combined treatment approach, estimating that associated risks are very limited.