Ciney, Belgium

A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer

Prospective, Multicenter, Single-Arm Observational Study to Confirm the Safety and Clinical Performance of the Oscar Peripheral Multifunctional Catheter for the Dilatation of Lesions in the Femoral, Popliteal and Infrapopliteal Arteries (BIO-OSCAR First)

This is a prospective, multicenter, all-comers observational study. Primary endpoint was procedural success (defined as a combination of successful primary target lesion crossing, residual stenosis of ≤30% following vessel preparation and before definite treatment) and absence of procedural complications (defined as target vessel perforation or rupture, acute occlusion, and distal embolization).

The Dragon PLC Trial (DRAGON-PLC)

Primary liver cancer (PLC) is the third most common cause of cancer death worldwide. Surgical resection is the mainstay for a curative approach as contemporary chemotherapy and immune-based therapies only lead to a median survival of 10-14 months. A complete surgical resection increases the median survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at an advanced stage and >70% of PLC patients are ineligible for an immediate surgical approach. There are different reasons that make a patient ineligible for surgery, one important reason is the risk of liver failure after the surgery due to a small remnant liver. This study aims to improve the oncological, radiological and surgical strategy to allow more patients to undergo liver resection safely, to improve quality of life and to extend overall survival at acceptable costs. Adequate function of the future liver remnant (FLR) is a prerequisite for surgical resectability. This is necessary in order to avoid liver failure after surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this risk, regenerative strategies based on preoperative calculation of the FLR volume and function are essential. Patients with technically resectable disease but predicted insufficient FLR volume or function are referred to as primarily unresectable or potentially resectable (PU/PR). These patients can undergo strategies that capitalize on the regenerative capacity of the liver which aim to preoperatively increase the FLR volume and function in order to allow surgery. Many of the patients that are primarily unresectable due to an insufficient FLR can become ultimately and safely resectable after the induction of adequate FLR-hypertrophy by the current standard, portal vein embolisation (PVE). However, 25% of patients do not show sufficient FLR growth after PVE and are unable to safely undergo resection. A new approach has been developed to improve this. Combined portal and hepatic vein embolisation (PVE/HVE) has great promise in terms of increasing FLR growth, resection rate (RR), safety and potentially, overall survival. Establishing PVE/HVE as the new standard could result in increased survival and a better quality of life (QoL) for patients.

Cisplatin (CIS) Administered As Dry Powder for Inhalation (DPI) in Patients with Stage IV Non-Small Cell Lung Cancer

The survival of patients with metastatic lung cancer has significantly improved with platinum-based treatments and, more recently, with targeted therapies and immunotherapies. However, despite therapeutic advances, lung cancer remains the world's leading cause of cancer-related death (approximately 2 million per year), due to innate or acquired tumour resistance to treatments. The combination of chemotherapy (platinum-doublets) and immunotherapy (immune checkpoint inhibitors) shows promising results in terms of overall survival (OS) and progression-free survival (PFS) for the treatment of first-line stage IV non-small cell lung cancer (NSCLC) patients, leading to such combinations becoming a real backbone of the Standard of Care (SoC) for NSCLC patients. These results may be attributable to the immunogenic effects of chemotherapy-induced tumour cell death, which, when used with immune checkpoint inhibitors, is an approach that may improve the clinical outcomes of cancer patients. However, conventional chemotherapy's severe systemic toxicities represent a limiting factor in terms of administered dose and frequency, requiring long rest phases (i.e., interruption of treatment) leading to a relatively limited frequency of chemotherapy treatment in current clinical practice (4 to 6 cycles of intravenous (iv) administration, all separated by a 3-week interruption period). This limitation, associated with high mortality, especially in the advanced stages of lung cancer, demonstrates that the treatments/combinations currently used are far from optimal. Administration of cisplatin by inhalation (pulmonary route) is a promising additional approach that may overcome the limitations of conventional chemotherapy and increase the efficacy of the current SoC via sustained local attack on the lung tumours of patients treated using immune checkpoint inhibitors with or without iv chemotherapy. Use of a dry powder inhaler (DPI) enables a high therapeutic response by delivering high local concentrations of a well-established active substance without the usual undesired reactions that limit the use of high doses when administered through the conventional systemic route. Thanks to limited systemic exposure to the cytotoxic active ingredient with the use of a dry powder inhaler, such add-on treatment enables considering 5 times weekly administration of inhaled chemotherapy at the patient's home. Increasing the frequency of local chemotherapy treatment in this way may enhance activation of the systemic anti-tumour immune response via local activation and stimulation of tumour-specific antigen release as a result of a safe, sustained and prolonged local effect, compared to the peak/short effect of iv chemotherapy. This study may provide insights into whether this add-on treatment might be a safe option for NSCLC patients.

Stereotactic Body Radiation Therapy for Inoperable Non-metastasized Pancreatic Adenocarcinoma

The occurrence of pancreatic cancer is increasing in Belgium. Although this type of cancer is severe, there are only a limited number of treatment options. The preferred treatment is usually surgery. However, this is only possible in certain circumstances. If surgery is not possible, chemotherapy is administered to improve survival. A combination of chemotherapy and SBRT followed by surgery if possible has already been used in some studies and will be investigated in a larger number of subjects with the TORPEDO study. A patient needs to sign an informed consent form before participating in the TORPEDO study. Participation in the TORPEDO study consists of the following phases: screening, induction chemotherapy, restaging and randomization, treatment, resectability assessment whether or not followed by surgery and a follow-up phase. During the screening phase, eligibility of the patient to participate in the study will be assessed. Demographics data, information regarding medical history, prior medications and adverse events will be recorded. Moreover, a clinical assessment, blood tests to assess general blood parameters, a CT chest/abdomen and MRI pancreas will be performed. Eligible patients (according to the inclusion criteria and exclusion criteria) will receive induction chemotherapy (standard of care) during 12 weeks. Either 6 cycles of mFOLFIRINOX or 3 cycles of gemcitabine / nab-paclitaxel will be administered. If, within one week after the end of chemotherapy (restaging), CT chest/abdomen and MRI pancreas do not show extrapancreatic disease and in absence of massive gastric or intestinal invasion, subjects will be randomized 1:1 to either treatment with chemotherapy (arm A) or treatment with a combination of chemotherapy and SBRT (5 x 8 Gy) (arm B). During the treatment phase, all subjects will receive 4 weeks of chemotherapy (either 2 cycles of mFOLFIRINOX or 1 cycle of gemcitabine/nab-paclitaxel). 7 to 28 days after the end of this chemotherapy treatment, subjects randomized in arm B will undergo SBRT (5 fractions of 8 Gy), preceded by the implantation of fiducial markers and simulation. 28 days after the end of the chemotherapy (arm A) or after the last SBRT fraction (arm B), various data will be collected (e.g. clinical assessment, blood tests such as determination of tumor marker CA19-9 level, CT chest/abdomen and MRI pancreas, questionnaires regarding quality of life and the occurence of adverse events) and resectability will be multidisciplinary determined. At 6 weeks (+/- 2 weeks) after chemotherapy (arm A) or SBRT (arm B), subjects considered suitable will have surgery. All subjects will receive another 8 weeks of chemotherapy (4 cycles of mFOLFIRINOX or 2 cycles of gemcitabine/nab-paclitaxel). The follow-up phase consists of ten-weekly follow-up visits during 2 years. These follow-up visits consist of a clinical assessment, CT chest/abdomen imaging, blood sampling, elicitation of AE's and assessment of the subject's quality of life through questionnaires. After these 2 years, patients will be followed by standard of care, six monthly during the following 3 years. After five years, patients will be followed on a yearly basis (standard of care). Follow-up data (survival status) will be collected.

Separation Surgery Followed by Stereotactic Ablative Body Radiotherapy (SABR) Versus SABR Alone for Spinal Metastases

In this study, patients with malignant epidural spinal cord compression (MESCC), Bilsky grade 1c, 2 and 3 who are ambulatory with or without aid (rollator, cane, one persons help) will be treated by separation surgery followed by SABR (5x 8.0 Gy postoperative) (control arm) or SABR alone (5x 8.0 Gy) (study arm). The primary objective of the study is investigating the effect of SABR compared to separation surgery followed by SABR in ambulatory patients with MESCC on retaining ambulatory function. The primary endpoint of the study is ambulatory function 3 months post treatment defined as: being able to walk 10m without aid; being able to walk 10m with aid (cane, rollator, one persons help, ...); not being able to walk. Secondary outcomes are local control, progression free survival, early and late adverse effects, quality of life, effect on pain and need for reintervention. For each participant, the study starts once written informed consent is provided and is composed by 4 study phases: a screening phase, randomisation, a treatment phase and a follow-up phase. The screening phase will allow for assessment of subject eligibility before randomisation and treatment. Demographic data, disease and spinal metastases characteristics and previous anticancer therapies will be recorded. Once all screening procedures are completed, eligibility will be determined according to the inclusion/exclusion criteria. Randomisation will be performed in a 1:1 ratio to the control arm (separation surgery followed by SABR) and the study arm (SABR) using an electronic randomisation tool in the eCRF. Treatment will be aimed to start as soon as possible, but certainly within 21 days after randomisation (surgery or upfront SABR). Surgical planning is done by the treating neurosurgeon in the participating center where the patient was included. Image-guided fractionated SABR using a SIB technique to the high-dose PTV will be delivered in 5 fractions of 8 Gy to a total of 40 Gy and to the conventional-dose PTV delivered simultaneously in 5 fractions of 4 Gy to a total of 20 Gy. At 6 weeks (+/-1 week) after the last RT session following information will be obtained (preferentially by digital consult): 1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, ...), not being able to walk 2. WHO performance status 3. Acute and late toxicity assessment: as measured with CTCAE version 5.0 4. Need for re-intervention, date and type of reintervention (surgery or radiotherapy), reason (wound infection, neurologic decline, loss of ability to walk or other) 5. Pain response: VAS pain score 6. Survival data (survival status, date of death, primary cause of death) At 3 and 6 months (+/-3 weeks) after the last RT session following information will be obtained by physical or digital consult: 1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, ...), not being able to walk 2. WHO performance status 3. Concomitant medications and systemic anticancer therapies 4. QoL according to the EORTC QLQ-C15 & BM22 questionnaires 5. Acute and late toxicity assessment: as measured with CTCAE version 5.0 7. Need for re-intervention, date and type of reintervention (surgery or radiotherapy), reason (wound infection, neurologic decline, loss of ability to walk or other) 6. Pain response: VAS pain score 7. Physical examination: body weight 8. Local control 9. Survival data (survival status, date of death, primary cause of death) At 12 and 24 months (+/-3 weeks) after the last RT session following information will be obtained (preferentially by digital consult): 1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, ...), not being able to walk 2. Need for re-intervention, type of reintervention 3. Survival data (survival status, date of death, primary cause of death) 4. Local control (only if information is available in medical record as per standard of care)

Proactive TDM Versus Standard Use of Biologics in Psoriasis

Rationale: Biologics are effective agents for the treatment of psoriasis. The newest generation of biologics block interleukin 17 and 23. Physicians always prescribe these drugs in a fixed dose, but this may lead to under- and overdosing in some patients. Underdosing may lead to inadequate response or loss of response over time. Overdosage, on the other hand, can lead to higher risk of side effects and higher costs for the healthcare system. In daily clinical practice, physicians often tackle this real-world issue by blind trial- and- error dose modifications or switching to another biologic. In this study, we want to rationalize these dose modifications and optimize dosing based on the drug concentrations, measured in the blood of the patient (i.e. therapeutic drug monitoring). Objectives: The primary goal is to assess if proactive TDM is non-inferior compared to standard of care with respect to sustained disease control, defined as an absolute PASI ≤ 2 OR a delta PASI from baseline ≥ 50% during at least 80% of all 3-monthly study visits over a period of 18 months, in patients with moderate to severe psoriasis treated with novel biologics (secukinumab, ixekizumab or guselkumab). Secondary goals are: To compare proactive TDM to standard of care with respect to disease activity, quality of life, treatment satisfaction and costs of treatment (cost-effectiveness) To identify baseline predictors for sustained disease control. To evaluate the cost-effectiveness of proactive TDM To evaluate the safety of proactive TDM. Study design: A multicentre, pragmatic, randomised, controlled, non-inferiority trial. Study population: Patients with moderate-to-severe psoriasis, treated with secukinumab or ixekizumab (IL-17 inhibitors) or guselkumab (IL-23 inhibitor) in daily clinical practice for at least 6 months on standard dosing (maintenance phase). A total of 210 patients will be randomized (1:1) to the intervention group (TDM based dosing) or continuation of usual care. Intervention: Stepwise treatment modifications based on drug levels: if the drug level is below/above the target, the dose of the biologic will be increased/decreased by stepwise interval shortening/lengthening - first modified by 33% and then 50% increase or decrease. If the target is still not reached at the next study visit, the dosing interval will be shortened or prolonged with one additional week at each additional visit until the target is reached. In case the dosing regimen shifts from dose increase to dose decrease or vice versa, the dosing interval will be shortened or prolonged with one additional week at each additional visit until the target is reached.

Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers

Approximately 360 evaluable patients determined to have high-risk localized or locally advanced PCa, with PSMA positive non-localized disease or a Decipher high score (> 0.6) will be enrolled to the Phase 3 trial. Subjects with PSMA positive non-localized disease for which a Decipher result cannot be obtained, will also be enrolled to the Phase 3 study. All Phase 3 subjects will be randomly assigned in a 1:1 ratio to receive darolutamide plus Luteinizing hormone releasing hormone (ant)-agonists (LHRHA), or darolutamide matched placebo plus LHRHA, for up to 96 weeks (24 months). All Phase 3 subjects will also receive primary standard of care (SOC) radiation therapy (RT). Subjects in Phase 3 should be commenced on an LHRHA and darolutamide or placebo within 14 days after randomization (unless started earlier) plus SOC RT. Only patients with a PSMA PET-CT showing more than 5 M1 lesions are allowed to receive docetaxel in both arms of the Phase 3 trial. Docetaxel should be started within 4 weeks from randomization. Randomization of Phase 3 subjects will be stratified by 1 versus > 1 high-risk features, N1 versus M1 PSMA positive versus PSMA negative disease, Decipher low/ intermediate versus high versus unknown score and clinical trial site. Approximately 133 evaluable patients determined to have localized PCa by PSMA PET/ CT (PSMA negative) with a low/ intermediate Decipher test score (≤ 0.6) will enter the non-randomized, Phase 2, single treatment arm, de-intensification study. Subjects with localized PCa by PSMA PET/ CT who return a high Decipher score (> 0.6) will be enrolled and randomized into the Phase 3 study. Subjects with localized PCa by PSMA PET/ CT for which a Decipher result cannot be obtained, will be deemed ineligible for study participation. All Phase 2 study subjects will receive darolutamide for the study duration for up to 96 weeks (24 months) and primary SOC RT.

Continuous Glucose Monitoring for Women with Gestational Diabetes

At diagnosis of GDM, women will receive education on the management of GDM with lifestyle and need to monitor glucose with SMBG. Within one week of GDM diagnosis, all participants will be asked to use a blinded CGM (Freestyle Libre Pro IQ,) during a run-phase. Women randomized to the control arm, will be asked to intermittently wear a blinded CGM sensor (Freestyle Libre Pro IQ) during 14 days at least two time points in pregnancy (at 31.0-33.6 weeks and between 36.0-38.6 weeks). For women diagnosed with early GDM (<20 weeks), blinded CGM will be needed 3 times in pregnancy with a first time at 20.0-23.9 weeks. Women randomized to the intervention arm will be recommended tu use the rt-CGM (Freestyle Libre 3) till the delivery. In line with normal routine, a 75g OGTT will be performed between 6-24 weeks postpartum to screen for glucose intolerance. Participants will be asked to also wear a blinded CGM (Freestyle Libre Pro IQ) at this last study visit.

First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)