The Hill

Researchers are evaluating the effectiveness and safety of adding Tersolisib (LY4064809/STX-478) to other anti-cancer drugs as the first treatment for adults with advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This phase 3 study focuses on participants whose cancer has a specific genetic change called a PIK3CA mutation and who have not received prior treatment for advanced breast cancer. The study aims to understand how well this treatment combination works and its safety over time. Participants will receive Tersolisib or a placebo, combined with a CDK4/6 inhibitor (Ribociclib, Palbociclib, or Abemaciclib) and endocrine therapy (Anastrozole, Letrozole, Exemestane, or Fulvestrant). All drugs are given orally except for Fulvestrant, which is given by injection into the muscle. The study includes two parts: Part 1 allows participants who have had up to two prior treatments for advanced breast cancer, including chemotherapy; Part 2 includes those with no prior treatment for advanced disease and classifies them as endocrine sensitive or resistant based on their cancer history. During the study, participants will be regularly assessed for cancer response, progression-free survival, and side effects. Researchers will monitor measurable disease or bone involvement and track overall response rates, including complete or partial tumor shrinkage. The study will continue as long as the treatment is helping without causing unbearable side effects. Follow-up may last up to five years to observe long-term outcomes and safety.

Researchers are evaluating how tirzepatide affects body weight and cardiovascular risk factors in adolescents with obesity who also have multiple weight-related health issues. This Phase 3 study aims to assess the safety and effectiveness of tirzepatide combined with healthy nutrition and physical activity. The study includes adolescents aged 12 to 17 years with obesity defined by a high body mass index (BMI) and at least two weight-related comorbidities such as hypertension, prediabetes, or high triglycerides. Participants will receive either tirzepatide or a placebo, both administered by subcutaneous injection once weekly during the primary 72-week study period. Alongside medication, all participants will follow lifestyle interventions focusing on nutrition and physical activity. After completing the initial 72 weeks and a 4-week safety follow-up, eligible participants who have not been off treatment for more than 12 weeks can continue tirzepatide treatment for an additional 156 weeks with ongoing lifestyle support. Throughout the study, up to 23 visits will monitor participants' BMI changes and improvements in weight-related health conditions. Researchers will measure the percentage change in BMI and assess whether participants show significant improvement or normalization in at least two comorbidities without new or worsening conditions over 72 weeks. Safety and efficacy will be closely tracked during the treatment periods and follow-up visits to understand tirzepatide's impact on adolescent obesity and related health risks.

Researchers are evaluating the effects of BMS-986368, a FAAH/MAGL inhibitor, on spasticity in people with Multiple Sclerosis (MS). This Phase 2 study aims to assess the drug's efficacy, safety, and tolerability by comparing three different doses of BMS-986368 to a placebo in participants who have experienced MS-related spasticity for at least six months. Participants will receive oral doses of BMS-986368 or placebo at specified times. The study includes four groups: three groups receive different doses of BMS-986368, and one group receives a placebo. Treatment is administered according to a set schedule, and the trial is conducted at multiple centers with a double-blind design to ensure unbiased results. During the study, participants' spasticity levels will be measured using the Total Numeric-transformed Modified Ashworth Scale focusing on the most affected lower limb at week 6. Additional evaluations include safety and tolerability assessments. Participants are monitored throughout the treatment period for changes in spasticity and any side effects. The study includes adults aged 18 to 70 years with specific MS-related disability and spasticity criteria.

Researchers are evaluating the addition of stereotactic body radiotherapy and durvalumab to a well-tolerated two-week chemotherapy and radiation treatment regimen for adults with locally advanced or metastatic esophageal cancer. This phase II clinical trial aims to see if combining chemotherapy, radiation, and immune therapy can better prevent cancer progression and improve swallowing difficulties in people with esophageal or gastro-esophageal junction cancer. Participants will receive 10 daily radiotherapy treatments over two weeks targeting the primary esophageal tumor, along with weekly intravenous chemotherapy including carboplatin and paclitaxel during the same period. Durvalumab, an immune therapy drug, will be given intravenously every four weeks starting at the beginning of radiation therapy and continued for up to 24 months or until the cancer worsens. Those with metastatic tumors will receive an additional three doses of radiotherapy given in one week, four weeks after the initial radiotherapy. Throughout the study, safety blood tests will be collected every two weeks starting at week 2 and then every four weeks from week 9 onward, with additional tests as needed. CT scans to assess tumor response will be done every six weeks until week 24, then every 12 weeks or until cancer progression. Participants will also complete questionnaires about their wellbeing and nutrition during the study. The primary outcome measured is progression-free survival at six months, meaning participants are alive without cancer worsening by that time.

Researchers are evaluating whether accelerated BEP chemotherapy is more effective than the standard BEP chemotherapy in males with intermediate and poor-risk metastatic germ cell tumors. This phase 3 trial focuses on patients with these tumor types, aiming to improve cure rates beyond those achieved with current treatments. The trial is led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group and addresses the need for better first-line treatments due to limited success and higher toxicity of previous strategies. The study compares two treatment regimens: standard BEP chemotherapy given every 3 weeks for 4 cycles and accelerated BEP chemotherapy given every 2 weeks for 4 cycles. Both regimens include Bleomycin, Etoposide, and Cisplatin administered intravenously at specified doses, plus supportive treatments with Pegylated G-CSF (Pegfilgrastim) and Filgrastim to help manage blood cell counts. The accelerated arm includes additional weekly doses of Bleomycin after the initial 4 cycles. These regimens are designed to test if faster cycling of chemotherapy drugs improves outcomes. Participants will be closely monitored from the time of randomization through up to 5 years for progression-free survival, which measures time until disease progression or death. Assessments include laboratory tests to check bone marrow, liver, and kidney function, as well as evaluations of overall health status. Participants must be able to start treatment within 14 days of randomization and comply with all study procedures. Safety and effectiveness of the treatments will be tracked throughout the study duration to determine if the accelerated regimen offers improved results.

Long bone defect (LBD) is a focal loss of bone tissue in any long bone of the arms or legs, often caused by trauma, tumors, or infection, with post-traumatic defects being the most common. Limb reconstruction for these defects is complex and currently lacks strong evidence-based treatment guidelines. This international, multicenter registry aims to collect detailed information about the prevalence, treatments, complications, and outcomes of long bone defects over a three-year period. The registry includes any treatment used for long bone defects, with treatment decisions made by individual clinicians based on patient characteristics. No specific treatment is dictated by the registry. The study plans to enroll at least 600 patients from participating sites worldwide. Surgical interventions and other therapies applied to treat bone defects will be documented along with patient-related and other defined outcome measures. Participants will undergo assessments at multiple time points including pre-operative, intraoperative, and follow-up visits up to 12 to 18 months after bone union. These assessments cover baseline characteristics, bone defect details, trauma evaluation, surgical findings, functional outcomes, quality of life, and radiological results. Data collected will help understand treatment strategies, identify challenges, and improve clinical evidence for managing long bone defects.

Fetal growth restriction (FGR) affects many pregnancies and is a major risk factor for stillbirth, preterm birth, and long-term health problems including brain injury. This trial studies whether giving melatonin to pregnant women with early-onset severe FGR can protect the fetal brain and improve children's neurodevelopmental outcomes. It is a phase 3, triple-blind, randomized, placebo-controlled trial involving multiple centers in Australia and New Zealand. Participants receive either melatonin tablets (10 mg three times daily, up to 30 mg per day) or placebo tablets that look identical but contain no active ingredient. Treatment begins after diagnosis of severe FGR between 23 and 31+6 weeks of pregnancy. The study includes sub-analyses based on gestational age at diagnosis to compare effects in early versus late-onset FGR. Throughout the study, children's neurodevelopment will be measured at 2 years of age. Researchers will monitor maternal and fetal health, fetal wellbeing, and collect data on birth outcomes. The main outcome is neurodevelopmental performance assessed between 24 and 36 months corrected age. Safety and tolerability of melatonin supplementation during pregnancy will also be evaluated over the course of the trial.

Researchers are evaluating the use of non-vitamin K oral anticoagulants (NOACs) compared to no anticoagulation in people who have experienced transient atrial fibrillation episodes triggered by stress and have additional risk factors for stroke. This multinational, investigator-initiated Phase 4 trial aims to prevent stroke and other serious cardiovascular events in this group by assessing the effects of NOACs on two main outcomes: the occurrence of non-hemorrhagic stroke or systemic embolism, and a combination of vascular death and other major cardiovascular problems, over a follow-up period lasting until the last participant reaches 24 months of observation. Participants in the study are randomly assigned to either receive one of several NOAC medications—edoxaban, apixaban, dabigatran, or rivaroxaban—with dosing adjusted as needed and chosen by their prescribing doctor, or to receive no oral anticoagulation. The treatment continues throughout the follow-up period. The trial is open-label, meaning both researchers and participants know which treatment is given. The study specifically focuses on patients who had transient atrial fibrillation related to stress, such as after certain surgeries or acute medical illness. During the study, participants undergo regular monitoring to track the incidence of stroke, embolism, vascular death, heart attacks, blood clots, and other cardiovascular events. Researchers collect information over up to two years to evaluate these outcomes. Safety and adherence to treatment are also monitored. This thorough follow-up helps determine the impact of NOAC treatment compared to no anticoagulation in this particular patient population.

Researchers are establishing an Australian group of patients diagnosed with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) to study its clinical features and how the condition progresses over time. They will assess participants using neuropsychological tests, brain imaging, genetic analysis, blood biomarkers, and retinal imaging to better understand CADASIL in this population. This observational study takes place across six sites in three Australian states, involving clinics, hospitals, and universities. Participants will undergo clinical examinations and complete questionnaires to gather medical history. Neuropsychological evaluations and brain MRI scans are included to monitor brain changes. Blood samples will be collected to analyze genetic status and biomarkers, while retinal imaging will provide additional insights. The study aims to track these measures over several years to observe disease progression. Participants are involved in regular assessments including online medical questionnaires, physical measurements like weight and height, blood pressure checks, various cognitive tests, and brain MRI scans at baseline and at intervals up to four years. The study measures cognitive function and neurological status through several standardized tests and imaging techniques. Safety and health monitoring continue throughout the study to understand long-term outcomes in CADASIL patients.

Researchers are studying the usefulness of family-based whole-genome sequencing (WGS) to test for cancer predisposition syndromes (CPS) in children and adolescents newly diagnosed with cancer. CPS are inherited disorders caused by mutations in specific genes that increase cancer risk. This study aims to understand how often CPS occurs in Australian children with cancer and to assess the psychosocial effects of germline sequencing on patients and their families. The main goal is to compare the ability of family-based WGS to identify CPS against traditional clinical methods like family history and tumor type analysis. Participants will undergo germline whole-genome sequencing involving the child and their family (trio sequencing). Identified genetic variants will be discussed in multidisciplinary meetings to decide on referrals to Cancer Genetics Clinics for further evaluation, follow-up, and genetic counseling. Additionally, a psychosocial study will examine the impact of this genetic testing on families. This approach is evaluated in every newly diagnosed child with cancer up to 21 years old. Throughout the study, researchers will assess the proportion of patients whose CPS is identified by WGS compared to those identified by clinical information over a two-year period. Participants aged 12 years and older, their parents or caregivers, and involved healthcare professionals will be part of the psychosocial component. The study collects information on genetic findings, clinical outcomes, and family experiences to determine the benefits and effects of family-based WGS in pediatric cancer care.