Leidschendam

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as a first-line treatment for patients with locally advanced or metastatic non-squamous non-small cell lung cancer NSCLC whose tumors express PD-L1 at levels of 1% or higher. This Phase III, randomized, double-blind, global study aims to compare these treatments to improve outcomes for this patient group. Participants will receive either rilvegostomig or pembrolizumab, each given intravenously on Day 1 of every 21-day cycle, combined with platinum-based doublet chemotherapy either carboplatin or cisplatin also given on Day 1 of each cycle for up to four cycles. After chemotherapy cycles, patients continue with rilvegostomig or pembrolizumab monotherapy combined with pemetrexed maintenance. The study follows patients for up to approximately six years to monitor treatment effects and safety. During the study, participants undergo assessments including imaging scans to measure tumor size, blood tests to evaluate organ function, and questionnaires about symptoms and quality of life. Researchers monitor overall survival and progression-free survival as primary outcomes, alongside other measures such as response duration and physical functioning. Safety is closely observed throughout, with study visits scheduled regularly during treatment and follow-up periods, lasting up to six years in total.

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with platinum-based chemotherapy compared to pembrolizumab combined with platinum-based chemotherapy as a first treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer mNSCLC whose tumors express programmed death-ligand 1 PD-L1. This Phase III global study focuses on patients with PD-L1 tumor cell expression of 1% or higher and aims to determine which treatment provides better overall and progression-free survival. Participants will be randomly assigned to one of two study groups one group will receive rilvegostomig plus carboplatin and either paclitaxel or nab-paclitaxel chemotherapy, while the other group will receive pembrolizumab plus the same chemotherapy options. Rilvegostomig and pembrolizumab are both given intravenously on Day 1 of each 21-day cycle, with chemotherapy given up to 4 cycles. Nab-paclitaxel may be administered on Days 1, 8, and 15 of each cycle. Treatment continues with rilvegostomig or pembrolizumab until disease progression or other criteria are met. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests to monitor organ function, and patient questionnaires about physical function and quality of life. Researchers will track overall survival, progression-free survival, response rates, and duration of response for up to approximately 6 years. Safety and immune response to rilvegostomig will also be evaluated. Participants will be closely monitored throughout the treatment and follow-up periods.

Researchers are evaluating the efficacy and safety of the combination of divarasib and pembrolizumab compared with pembrolizumab combined with pemetrexed and either carboplatin or cisplatin. This study focuses on adults with previously untreated, advanced or metastatic non-squamous non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The goal is to assess these treatments as first-line options in this specific lung cancer population. Participants will be randomly assigned to one of two groups. One group will take divarasib orally once daily and receive pembrolizumab through an intravenous infusion every three weeks. The other group will receive pembrolizumab, pemetrexed, and either carboplatin or cisplatin via intravenous infusions every three weeks. Treatment continues with these schedules, following the study protocol for up to approximately five years of follow-up. During the study, participants will have regular assessments to monitor their health and response to treatment. These include imaging and clinical evaluations to measure progression-free survival and overall survival for up to five years. Researchers will also track quality of life, symptom changes, treatment side effects, and adverse events using questionnaires and patient-reported outcomes. Safety monitoring and detailed evaluations will help understand the effects of the treatments over the study duration.

Researchers are evaluating 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 focuses on patients without distant metastasis who show ctDNA positivity during screening. The study aims to assess whether elacestrant can improve outcomes over the current standard endocrine treatments. The study consists of two phases. First, during the ctDNA screening phase, patients on standard adjuvant endocrine therapy will have plasma samples collected every six months for about 5.7 years to detect ctDNA. Patients who test positive will undergo imaging to confirm no distant metastasis and then be randomized 11 to either continue their current endocrine therapy or receive elacestrant 400 mg orally once daily. Treatment duration depends on prior endocrine therapy length, lasting between 2 to 6 years. Intensive follow-up with ctDNA testing and imaging occurs for up to 3 years after randomization. Participants will be monitored closely with blood tests for ctDNA at weeks 4, 16, and every 16 weeks thereafter, along with yearly mammograms, bone scans, and CT scans every 16 weeks to detect metastases or recurrences. Safety, quality of life, and overall survival are assessed throughout, with follow-up continuing until three years after the last patient enrolls. The primary outcome measured is distant metastasis-free survival at 6.25 years after the first randomization.

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 a new method of stereotactic radiotherapy for treating brain metastases in this randomized phase II trial. The study compares the current standard stereotactic radiotherapy SRT delivered in one or three doses with a fractionated approach fSRT given in five doses. The goal is to find a potentially safer treatment that reduces long-term side effects like brain necrosis, which affects up to 40% of patients depending on tumor size and radiation dose. One group of participants will receive SRT in one or three sessions with doses ranging from 8 Gy up to 15-24 Gy. The other group will receive fSRT spread over five sessions with doses of 7 Gy up to 35 Gy, or for brain stem metastases, five sessions of 6 Gy up to 30 Gy. This treatment phase compares these two radiation schedules to assess differences in safety and tumor control. Participants will be monitored for survival, side effects, and quality of life for two years after treatment. Researchers will track the occurrence of brain necrosis or tumor recurrence, need for additional treatments, brain recurrences, corticosteroid and anti-epileptic drug use, and any grade 2 or higher toxicities. This thorough follow-up includes patient-reported outcomes and medical assessments to understand the treatments impact over time.

Researchers are evaluating treatments for patients with locally recurrent rectal cancer in this multicenter, open-label, randomized phase III clinical trial. The study compares two approaches for neoadjuvant treatment before surgery induction chemotherapy followed by chemoradiotherapy and surgery versus chemoradiotherapy and surgery alone. The purpose is to determine whether adding induction chemotherapy improves surgical outcomes and cancer control. Participants will be randomly assigned to one of two groups. The experimental group receives induction chemotherapy using either CAPOX, FOLFOX, or FOLFIRI regimens, followed by chemoradiotherapy and then surgery. The control group receives chemoradiotherapy followed by surgery without induction chemotherapy. Radiotherapy doses vary based on prior treatment history, and surgery type depends on tumor location. Intraoperative radiotherapy is optional. During the study, patients will undergo MRI and clinical assessments to confirm resectability and monitor response to treatment. Researchers will assess the proportion of patients with clear surgical margins within one month of surgery, along with long-term outcomes such as survival and recurrence over five years. They will also evaluate treatment toxicity, compliance, surgical complications, radiological response, and quality of life at multiple time points. Follow-up includes monitoring up to five years after treatment to capture disease progression and survival.

Researchers are studying women with node-positive breast cancer who receive neoadjuvant systemic therapy NST, which includes chemotherapy with or without immunotherapy. The study aims to understand the safety and quality of life effects of using less invasive methods compared to more invasive axillary staging and treatment after NST. This is important because patients whose lymph nodes show no remaining cancer after NST may not benefit from extensive lymph node removal, but more evidence is needed about the safety and impact of less invasive approaches. This multicenter observational study collects detailed information on patients treated with NST for node-positive breast cancer. It gathers data about the cancer, staging methods before and after NST, and treatment details from medical records. Patients complete questionnaires about their quality of life at diagnosis, and then 1 and 5 years later. The study database is maintained by the Netherlands Cancer Registry and aims to inform future treatment guidelines. Participants provide information through patient-reported outcome measures and undergo regular clinical follow-up to monitor disease-free survival, breast cancer-specific survival, overall survival, and rates of cancer recurrence in the lymph nodes over five years. Quality of life is assessed using several validated tools at baseline and during follow-up. The study results will help balance treatment decisions between less and more invasive options and support shared decision making for women with this breast cancer type.

Researchers are evaluating a combined treatment approach for men with high risk prostate cancer to determine if it is safe to use several optimized therapies together. This includes delivering a higher dose of radiation to the tumor while irradiating the prostate and lymph nodes more intensively but with fewer hospital visits. The study aims to reduce androgen deprivation therapy as much as possible to minimize side effects while comparing cancer outcomes and treatment toxicity. The treatment being studied involves hypo fractionated pelvic radiotherapy with a focal boost to the primary tumor in the prostate, along with elective lymph node irradiation and minimized use of androgen deprivation therapy. This approach combines recent advances shown to improve outcomes individually but not previously combined into one comprehensive treatment. The study is designed as a prospective cohort with a matched control group. Participants will undergo regular clinical follow-up without additional tests or visits beyond standard care. Researchers will assess biochemical recurrence-free survival over 5 years and monitor late gastrointestinal and genitourinary side effects, including erectile dysfunction, at 6 months and 2 years. Secondary outcomes include metastasis-free survival, overall survival, and patterns of cancer recurrence. The estimated risks from combining these treatments are considered very limited, and the overall burden for participants is low.