Schiedam

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are evaluating the safety and effects of the medicine PF-07248144 combined with fulvestrant for treating hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. This type of breast cancer involves cancer cells that grow in response to hormones like estrogen and progesterone but have little or no HER2 protein. The study focuses on people whose breast cancer worsened after treatment with cyclin dependent kinase (CDK) 4/6 inhibitor therapy. The trial is a phase 3, open-label, randomized study comparing PF-07248144 plus fulvestrant to other therapies chosen by doctors. Participants will receive either PF-07248144 tablets daily at home in 28-day cycles combined with fulvestrant injections at the clinic, or the usual treatment of everolimus tablets with endocrine therapy (either exemestane or fulvestrant). The study doctor will help decide the hormone therapy before starting treatment. The trial compares the experiences of those taking PF-07248144 plus fulvestrant with those receiving standard treatments to assess safety and effectiveness. During the study, researchers will monitor participants for disease progression or death, using blinded independent central review based on standard tumor response criteria. The main outcome measure is progression-free survival for up to about 2 years from randomization. Regular assessments, including clinical visits for injections and evaluations, will help track treatment effects and safety throughout the study.

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 evaluating the safety and effectiveness of combining JSB462 (luxdegalutamide) at doses of 100 mg and 300 mg once daily with abiraterone, compared to an androgen receptor pathway inhibitor (ARPI) such as abiraterone or enzalutamide in adult men with metastatic hormone-sensitive prostate cancer (mHSPC). This Phase II study aims to select the recommended dose of the combination for further Phase III trials by assessing overall efficacy, safety, tolerability, and pharmacokinetics in participants. Participants receive JSB462 orally every day at either 100 mg or 300 mg doses continuously from randomization until disease progression, unacceptable side effects, death, or decision to stop treatment. Alongside this, abiraterone (1000 mg daily) or enzalutamide (160 mg daily) is also given continuously under the same conditions. The study includes a 28-day screening period, followed by the treatment period and then a 30-day post-treatment safety follow-up. After this, a long-term follow-up phase collects ongoing safety, efficacy, and survival data until the study ends. Throughout the study, participants undergo monitoring for prostate specific antigen (PSA) response, adverse events, dose adjustments, and duration of treatment exposure. Safety visits occur 30 days after treatment stops, and long-term follow-up tracks participant health until study completion. The total participation duration varies depending on individual treatment response and follow-up schedules, with assessments continuing for up to approximately 75 months from randomization.

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.

Researchers are evaluating the effects of survodutide in adults aged 18 years and older who have a confirmed liver condition called non-alcoholic steatohepatitis (NASH) or metabolic-associated steatohepatitis (MASH). Eligible participants must have a body mass index (BMI) of 27 kg/m2 or higher, or at least 25 kg/m2 if they are Asian. The study excludes those with other chronic liver diseases or a history of significant alcohol use. The main goal is to see if survodutide can improve liver function and delay progression of liver damage over time. Participants are randomly assigned to receive either survodutide or a placebo, with twice the chance of receiving survodutide. Both treatments are given as weekly injections under the skin using a pre-filled syringe. Alongside treatment, all participants receive regular counseling to encourage healthy diet and exercise habits. The study lasts up to four and a half years, with frequent visits or remote video calls during the first year and five months, then quarterly visits thereafter. During the study, doctors monitor participants' health, including body weight and liver function using imaging tests at certain visits. Participants complete symptom questionnaires to help assess their condition. Researchers track outcomes such as survival, need for liver transplant, worsening liver disease, and liver-related complications. Safety and any side effects are closely watched throughout the study period to understand the treatment's impact.

Researchers are evaluating the effects of survodutide on adults living with obesity who have a liver disease called non-alcoholic steatohepatitis (NASH) or metabolic associated steatohepatitis (MASH), along with moderate or advanced liver fibrosis. The study focuses on whether survodutide can improve liver function and reduce liver damage in these participants. This Phase III trial aims to assess both the effectiveness and safety of survodutide over a long-term period. Participants are randomly assigned to one of two groups: one receiving weekly injections of survodutide and the other receiving placebo injections that look like the medicine but contain no active drug. The doses of survodutide are gradually increased until the target dose is reached. All participants receive counseling to support healthy diet changes and regular exercise throughout the study. The study lasts up to 7 years, with frequent visits to the study site or remote video calls. In the first year, visits occur every 2 weeks, then every 4 to 6 weeks, and later every 3 months alternating between in-person and remote. Throughout the study, researchers monitor participants' health, liver condition through imaging and biopsies, body weight, digestive system effects, and questionnaires about symptoms and quality of life. The main outcomes include liver fibrosis improvement, resolution of MASH without worsening fibrosis, and long-term safety and efficacy measures.

Researchers are investigating the effectiveness of adding liothyronine (LT3) to levothyroxine (LT4) treatment in patients with autoimmune hypothyroidism who continue to experience significant tiredness despite normalized thyroid hormone levels on LT4 alone. This phase 3 trial addresses the issue that LT4 monotherapy may not achieve the natural balance of thyroid hormones, as some patients still feel tired. The study also explores genetic factors that might influence treatment response. The study begins with a run-in period where all participants switch to a standardized LT4 preparation to stabilize thyroid hormone levels. During this 4-8 month period, doses are adjusted to maintain normal TSH levels, and patients with unstable TSH or heart abnormalities are excluded. Those with persistent tiredness and stable hormone levels then enter a 1-year double-blind randomized trial, receiving either LT4 combined with LT3 or LT4 with placebo. Regular visits occur at baseline and weeks 8, 16, 26, 39, and 52, including dose adjustments and comprehensive assessments. Participants complete questionnaires about tiredness, quality of life, and medical resource use at every visit. Additional blood tests for genetics and thyroid metabolites occur at baseline and 52 weeks, along with monitoring of bone, cardiovascular, metabolic, and brain health through scans, ECGs, and neurocognitive tests in subgroups. The main outcome is the change in tiredness scores over 52 weeks, with safety and treatment effects closely monitored throughout the study.

Researchers are evaluating whether chemotherapy can be safely skipped for people with certain early-stage triple-negative breast cancers that have favorable features, after they have had surgery and radiation treatment. The study also looks at whether avoiding chemotherapy improves quality of life. Participants make their treatment choice together with their doctor, deciding whether to receive chemotherapy or not. The study compares two groups: one receiving adjuvant chemotherapy following local or national guidelines, and another group receiving no adjuvant chemotherapy. All participants have already undergone curative breast surgery and radiation if needed. The study focuses on those with low stage triple-negative breast cancer who have high levels of specific immune cells (stromal tumor-infiltrating lymphocytes) in their tumor tissue. Participants will be followed for up to 96 months after the last patient joins the study to measure how long they remain free from disease recurrence. Researchers will monitor cancer outcomes and quality of life during this time. The study includes assessments based on pathological tumor features, imaging to confirm no spread of disease, and reviews of tissue samples to confirm immune cell levels. Safety and treatment effects will be carefully observed throughout the follow-up period.

Researchers are evaluating the Photo Acoustic Imager 3+ (PAM3+) device to detect breast lesions, both malignant and benign, in women referred to an outpatient breast clinic. This Phase 2 study aims to assess the negative predictive value of the PAM3+ and also evaluates its diagnostic accuracy in locating and measuring breast lesions compared to BI-RADS scores, breast density, and conventional imaging methods. Additional goals include assessing usability, patient satisfaction, and safety while developing a PAM3+ lexicon to support clinical use. In this study, patients will lie face down with one breast placed in the aperture of the PAM3+ device, supported by a plastic cup filled with water. Infrared light is emitted onto the breast, absorbed by red blood cells, causing tiny movements in the water detected by ultrasound sensors. These signals combine to create a 3D image of the breast. The study is conducted in an outpatient setting, focusing on females over 18 years old referred for possible breast lesions. Participants will undergo the PAM3+ scanning procedure while researchers collect data on the device's performance throughout the study, which lasts about one year on average. Researchers will monitor diagnostic accuracy, patient satisfaction, and safety. Participants must complete questionnaires and provide informed consent. The study includes ongoing assessments to confirm the PAM3+ device's ability to detect breast lesions reliably and safely in clinical practice.