Mons

Despite some encouraging data, systemic treatment of CNS metastases from solid tumors remains experimental. Better knowledge on the evolving epidemiology and biology of BM are key elements for the development of new treatment strategies and identification of promising therapeutic targets for new compounds. Further biological findings may help to better understand the heterogeneity between the primary tumor and the CNS metastases and to identify new targets for therapy thus improving patients' outcome. In this context, the Oncodistinct network and the Jules Bordet institute propose to build a multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm. The BrainStorm program will focus on patients with newly diagnosed non-CNS metastatic solid tumors with high risk of developing CNS metastases and will allow building a large clinico pathological database for CNS metastases including ctDNA analyzes from CSF samples. Substudies will be proposed at each time-period with the final objective to develop innovative treatment approaches and strategies.

Researchers are evaluating the safety and effectiveness of divarasib combined with pembrolizumab compared to pembrolizumab with pemetrexed and either carboplatin or cisplatin. The study focuses on adults with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. This is a Phase III trial aiming to improve first-line treatment options for these patients. Participants will receive one of two treatment combinations. One group will take divarasib orally once daily along with pembrolizumab given through an intravenous infusion every three weeks. The other group will receive pembrolizumab with pemetrexed and either carboplatin or cisplatin, all administered by intravenous infusion every three weeks. Treatment schedules and dosages are carefully monitored during the study. Throughout the study, participants will be regularly assessed for progression-free survival and overall survival, with follow-up lasting up to approximately five years. Researchers will perform various evaluations including tumor measurements and safety monitoring. This long-term observation helps to understand the treatments' effects and safety over time, supporting informed decisions for future lung cancer therapies.

Researchers are evaluating the effectiveness of two treatment combinations, 5-FU with nanoliposomal irinotecan (NALIRI) and 5-FU with nanoliposomal irinotecan plus oxaliplatin (NALIRINOX), for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) that has progressed after initial gemcitabine-based therapies. This phase 2 randomized study focuses on patients who are physically fit with good performance status (ECOG 0-1). The main goal is to measure how long patients live without disease progression after starting these treatments. Participants will be randomly assigned to one of two groups. The control group receives NALIRI with 5-FU and leucovorin, while the investigational group receives NALIRINOX, which adds oxaliplatin to the same combination. Dosing varies between groups: NALIRI is given at 70 mg/m² with 2400 mg/m² of 5-FU and 400 mg/m² of leucovorin, while NALIRINOX includes 50 mg/m² of nanoliposomal irinotecan, 2400 mg/m² of 5-FU, 400 mg/m² of leucovorin, and 60 mg/m² of oxaliplatin. The study assesses safety, side effects, tumor response via imaging and tumor markers, and overall survival alongside progression-free survival. During the study, participants will undergo regular assessments including imaging scans to evaluate tumor size and response, blood tests to monitor safety and tumor markers, and evaluations of side effects using standard criteria. Researchers will track progression-free survival at day 85 from randomization as the primary outcome. The study also monitors overall survival and treatment tolerability. Participants must be monitored for safety throughout, with follow-up visits to assess long-term outcomes and treatment effects.

Researchers are evaluating the effectiveness and safety of a combination treatment called triple therapy, which includes bempedoic acid, ezetimibe, and either atorvastatin or rosuvastatin. This study focuses on patients with primary hypercholesterolemia or mixed dyslipidemia who are at high or very high cardiovascular risk. The goal is to understand how well this combination lowers LDL cholesterol (LDL-C) in a real-world clinical setting. The study observes patients who have already started triple therapy within the last four weeks. No drugs are administered as part of this study; instead, it monitors the ongoing treatment with bempedoic acid combined with ezetimibe and either rosuvastatin or atorvastatin. The study measures LDL-C changes from baseline to eight weeks after starting triple therapy and continues follow-up for one year to assess lipid goal achievement, adherence to therapy, treatment changes, laboratory value shifts, and occurrence of cardiovascular events. Participants will have their LDL-C levels and other lab values assessed at baseline, eight weeks, and one year after starting triple therapy. Researchers will collect data on adverse events, adherence to treatment, and cardiovascular outcomes such as heart attack, stroke, death from cardiovascular causes, and coronary procedures during the follow-up year. The study also tracks treatment pathways and changes over this period to better understand real-world use and effectiveness of this triple therapy approach.

Researchers are investigating the use of Oncobax42-AK, a live bacterial product containing Akkermansia muciniphila, in patients with advanced solid tumors, specifically non-small-cell lung cancer (NSCLC) and renal cell carcinoma (RCC). This study is based on findings that the presence of Akkermansia in the gut is linked to better responses to immunotherapy in these cancers. In preclinical models, giving patients the Akkermansia p2261 strain orally helped reverse resistance to PD-1 immunotherapy, and this trial aims to evaluate this approach in humans. Participants who lack Akkermansia in their gut microbiota, confirmed by stool testing, will receive oral Oncobax42-AK alongside their ongoing immunotherapy treatment. The study focuses on patients with stage IV non-squamous NSCLC or clear cell RCC who meet specific criteria such as PD-L1 expression above 50% for NSCLC and stable disease status by iRECIST criteria. The treatment is administered to improve the effectiveness of their current immunotherapy regimen. During the study, participants will be monitored for tumor response over a 9-month period, with the main outcome being the objective response rate. Evaluations include measuring lesions by iRECIST, assessing blood parameters like hemoglobin and albumin levels, and monitoring for safety and adverse events. Researchers will closely follow performance status and laboratory tests to ensure participant safety throughout the trial.

Researchers are evaluating the effectiveness, safety, and patient-reported outcomes of standard treatments for people with relapsed or refractory multiple myeloma in real-world clinical settings. This study follows participants over 24 months to observe how current standard care works for those who have previously received treatment for this condition. The research includes participants who meet specific diagnostic criteria and have measurable disease based on recognized myeloma guidelines. The study does not involve any experimental treatment; instead, it observes patients receiving standard care as decided by their doctors. Participants include those who have undergone multiple prior therapies, including specific drug classes and targeted treatments, depending on the study period. The study covers different periods with slightly varied eligibility and treatment histories, including a group starting talquetamab treatment for relapsed or refractory multiple myeloma. Participants will be monitored for up to 52 months to evaluate their response to treatment, including overall response rates. Researchers will collect data on their health status, treatment history, and patient-reported outcomes. Safety and effectiveness will be assessed based on clinical evaluations and disease progression as determined by their healthcare providers throughout the study period.

Researchers are evaluating the effectiveness and safety of Afimkibart (RO7790121) as both an induction and maintenance treatment for people with moderately to severely active Crohn's disease in this Phase III, multicenter, double-blind, placebo-controlled study. The goal is to understand how well Afimkibart works compared to placebo in managing symptoms and disease activity over time. Participants will receive either Afimkibart or a matching placebo. Afimkibart is given both as an intravenous infusion and as a subcutaneous injection. This treat-through study means participants continue on the assigned treatment throughout the study period, allowing evaluation of both initial and ongoing therapy effects. During the study, participants will be regularly assessed to measure clinical remission using the Crohn's Disease Activity Index (CDAI) and to check for endoscopic response at week 52. Researchers will monitor safety and treatment effects throughout, with the entire participation lasting up to one year. Assessments include clinical evaluations and endoscopic examinations to track disease changes and treatment impact.

Researchers are evaluating whether adding zilovertamab vedotin to standard treatment helps people with previously untreated diffuse large B-cell lymphoma (DLBCL) live longer without their cancer growing or spreading. This Phase 3 study compares zilovertamab vedotin combined with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) against the standard regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The goal is to see if the new combination improves progression-free survival. Participants receive treatments through intravenous infusions of study drugs including zilovertamab vedotin, rituximab or its biosimilar, cyclophosphamide, doxorubicin, and vincristine, along with oral prednisone or prednisolone as per approved guidelines. Some may receive rescue medication such as granulocyte colony-stimulating factor (G-CSF) if needed. The study is open-label and conducted across multiple centers. During the study, participants are closely monitored for how long they live without their disease worsening, with follow-up up to approximately 50 months. Assessments include imaging scans like PET to evaluate disease status, heart function tests, and regular evaluations of overall health and side effects. Safety is monitored throughout, and researchers measure progression-free survival as the primary outcome to determine the effectiveness of the treatments.

Researchers are investigating a new approach to treat patients with stage IV non-small cell lung cancer (NSCLC) by combining chemotherapy and immunotherapy. This combination has shown promising results in improving overall survival and progression-free survival. However, traditional chemotherapy often causes severe side effects that limit the dose and frequency patients can receive. This trial explores delivering cisplatin, a chemotherapy drug, via inhalation using a dry powder inhaler to increase local drug concentration in the lungs while reducing systemic side effects. This method may offer a safer and potentially effective option for patients with advanced NSCLC. The study tests ascending doses of inhaled dry powder cisplatin (CIS-DPI) administered once daily for five consecutive days followed by two days off each week. Doses range from 2.5 mg up to a theoretical maximum of 30 mg. The inhalation is delivered through a single-use capsule-based device. This treatment is given in addition to the current standard of care, which may include immune checkpoint inhibitors and intravenous chemotherapy. The trial includes a dose escalation phase to determine the maximum tolerated dose and a safety expansion phase to recommend the optimal dose for further studies. Participants will undergo regular assessments including imaging scans, laboratory tests, and lung function measurements to monitor safety and response to treatment. Researchers will evaluate the maximum tolerated dose and safety profile over 12 weeks. Patients must be able to use the inhaler device and comply with scheduled visits and procedures. The study aims to improve treatment by allowing more frequent local chemotherapy administration, potentially enhancing the immune response against lung tumors while minimizing side effects.

Researchers are evaluating and comparing standard neoadjuvant treatment options for older patients, aged 70 years and above, who have high-risk stage II or stage III rectal cancer. This multicenter, open-label, randomized pragmatic clinical trial aims to study the effectiveness and safety of conventional neoadjuvant therapy versus total neoadjuvant therapy in this patient group. Participants will be randomly assigned to one of two treatment groups. The conventional arm includes either short-course radiotherapy (5 daily fractions of 5 Gy) followed by surgery or watch & wait, with optional adjuvant chemotherapy, or long-course chemoradiotherapy (25-28 fractions of 1.8-2.0 Gy combined with chemotherapy) followed by surgery or watch & wait, and optional adjuvant chemotherapy. The total neoadjuvant therapy arm involves different regimens at the investigator's discretion, including RAPIDO, RAPIDO light, and OPRA regimens, combining radiotherapy, chemotherapy, and surgery or watch & wait. Each regimen varies by radiation dose, chemotherapy duration, and sequence. During the study, participants will undergo treatments as per their assigned group. Researchers will monitor overall survival, progression-free survival, peripheral sensory neuropathy, and grade 3 or higher toxicities at 3 years after randomization. The study involves assessments of clinical response and adherence to treatment protocols. Safety and efficacy will be tracked throughout the study period to evaluate long-term outcomes for these older patients with locally advanced rectal cancer.