Sao Luis

Researchers are evaluating the efficacy and safety of opevesostat combined with daily corticosteroids compared to alternative treatments abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer mCRPC who have previously been treated with one next-generation hormonal agent NHA. The study aims to determine if opevesostat offers better control of disease progression assessed by radiographic progression-free survival, including participants with and without androgen receptor ligand binding domain mutations. Overall survival has also been included as a secondary outcome measure. Participants are randomly assigned to one of two groups. One group receives opevesostat 5 mg orally twice daily, plus dexamethasone 1.5 mg and fludrocortisone acetate 0.1 mg orally once daily, continuing until disease progression. Hydrocortisone is available as a rescue medication if needed. The other group receives either abiraterone 1000 mg once daily with prednisone 5 mg twice daily or enzalutamide 160 mg once daily, also until disease progression. This open-label, phase 3 study compares these two treatment approaches in a parallel design. During the study, participants undergo regular assessments including imaging scans to measure disease progression, safety monitoring, and evaluations of overall survival and quality of life. Researchers track radiographic progression-free survival for up to 52 months and secondary outcomes such as overall survival, time to new treatments, pain progression, and prostate-specific antigen PSA responses for up to approximately 82 months. Participants are closely monitored for adverse events and treatment tolerability throughout the study duration, which spans several years.

Researchers are conducting a Phase III, randomized, open-label multicenter study to evaluate the effectiveness and safety of giredestrant compared with fulvestrant. Both drugs are combined with the investigators choice of a CDK46 inhibitor palbociclib, ribociclib, or abemaciclib in participants with estrogen receptor-positive ER, HER2-negative advanced breast cancer who have become resistant to prior adjuvant endocrine therapy. Participants will be randomly assigned to one of two groups one group will receive giredestrant 30 mg orally daily on Days 1-28 of each 28-day cycle, while the other will receive fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and Day 1 of subsequent 28-day cycles. Both groups will also receive a CDK46 inhibitor chosen by the investigator, with dosing schedules depending on the specific inhibitor selected. Preperimenopausal women and men will receive a luteinizing hormone-releasing hormone LHRH agonist during treatment. Participants will be assessed for progression-free survival over up to 5 years, with additional measures including overall survival, response rates, duration of response, clinical benefit, and quality of life. Safety will be monitored through adverse event reporting, vital signs, and laboratory tests during treatment and up to 28 days after the last dose. The study is led by Hoffmann-La Roche and aims to provide detailed information on the treatments effects in this patient population.

Researchers are investigating the effects of crizanlizumab compared to a placebo in adolescents and adults with Sickle Cell Disease who experience frequent vaso-occlusive crises VOCs. This Phase III, randomized, double-blind study involves patients aged 12 years and older who have had 4 to 12 VOCs managed by healthcare professionals in the past year. The study evaluates the safety and effectiveness of crizanlizumab with or without standard hydroxyureahydroxycarbamide therapy. Participants are randomly assigned in a 21 ratio to receive either crizanlizumab at a dose of 5 mgkg or a placebo, both given alongside standard care. The treatment is administered intravenously as a concentrate for infusion. The study is stratified by hydroxyurea use and geographical region to ensure balanced groups. The main treatment period lasts for one year. During the study, participants will attend regular visits for treatment and monitoring. Researchers will assess the number of healthcare-managed VOCs, including those treated in person or via remote consultation, and measure various other outcomes such as time to first VOC, VOC duration, antibody development to crizanlizumab, adverse events, and changes in hemoglobin levels. Safety and efficacy will be observed over two years, with detailed documentation of VOC events and other health assessments throughout participation.

Researchers are evaluating whether the combination of vicadrostat BI 690517 and empagliflozin helps adults with heart failure who have symptoms and a left ventricular ejection fraction LVEF of 40% or more. This phase III study is designed to compare the effects of vicadrostatempagliflozin tablets versus placeboempagliflozin tablets on heart failure outcomes. The study aims to understand if this combined treatment improves health and reduces heart-related events. Participants are randomly assigned to one of two groups one group takes vicadrostat plus empagliflozin tablets once a day, and the other takes placebo plus empagliflozin tablets once a day. The study has no fixed duration and continues as long as participants benefit and tolerate the treatment. Throughout the study, participants visit their doctors regularly for health checks, and study staff may also contact them by phone to monitor well-being and any side effects. During the study, researchers monitor participants health through regular doctor visits and phone contacts. They collect data on heart-related events such as cardiovascular death, hospitalizations for heart failure, and urgent visits for heart failure over up to 42 months. Participants also answer questions about their symptoms and well-being. The study carefully tracks safety and treatment tolerance while gathering information to determine if the combined treatment helps people with heart failure.

Researchers are conducting a retrospective observational cohort study to evaluate clinical, pathological, and treatment data of people diagnosed with adrenocortical carcinoma since the year 2000. This rare cancer has a notably higher incidence in certain regions of Brazil, partly due to a common genetic mutation called TP53-R337H. The study aims to characterize this patient group and identify factors that influence outcomes, focusing on cases from major Brazilian treatment centers. Participants in this study are identified based on past clinical records rather than receiving new treatments. The study collects data from medical evaluations and follow-ups conducted at reference centers, including initial diagnosis and recurrences from 2000 onward. There are no interventions or experimental treatments given during this observational study. Participants involvement includes reviewing their medical history and clinical data over approximately 18 months. Researchers will analyze demographic and clinical characteristics from existing records to better understand the disease in this population. The study does not involve active treatment but focuses on data collection and analysis for improved knowledge of adrenocortical carcinoma in Brazil.

This research aims to map breast and prostate cancer in patients treated through the Brazilian Unified Health System by performing complete sequencing of tumor somatic and germline exomes. It focuses on understanding molecular variants in tumors, which can affect treatment response and disease prognosis. The project also seeks to identify hereditary genetic syndromes and collect data on the populations ancestry for the Brazilian Ministry of Healths National Precision Genomics and Health Program, Genomas Brasil. The study includes two groups 745 patients with HER2-positive and triple-negative breast cancer who underwent neoadjuvant therapy followed by surgery, and 137 patients with metastatic prostate cancer. Sequencing involves somatic and germline whole exome analysis for prostate and HER2-positive breast cancer, and somatic whole exome with germline whole genome sequencing for triple-negative breast cancer. Participants will provide tumor tissue and blood samples for genomic analysis. Researchers will characterize complete somatic and germline exomesgenomes within 12 months, identify genetic variants related to tumor prognosis and treatment response, and count patients with mutations in cancer-predisposing genes. The study runs until 2026 and data will support precision oncology efforts in Brazil.

Researchers are evaluating palazestrant OP-1250 compared to standard endocrine therapies for adults with ER-positive, HER2-negative advanced or metastatic breast cancer that has progressed after endocrine therapy combined with a CDK46 inhibitor. This international phase 3 trial aims to assess the safety and effectiveness of palazestrant versus fulvestrant or aromatase inhibitors such as anastrozole, letrozole, or exemestane. Participants are randomly assigned to receive either palazestrant daily on a 28-day cycle at doses of 90 mg or 120 mg during the dose-selection phase, or the standard-of-care endocrine therapy including fulvestrant administered on specific days or one of the aromatase inhibitors given daily on similar cycles. The trial includes an initial dose-selection period with about 120 participants, followed by a larger randomized phase with approximately 390 participants receiving the selected dose of palazestrant or standard treatment. Throughout the study, participants will be monitored for adverse events, dose adjustments, and drug discontinuations up to 16 weeks. Researchers will measure progression-free survival for up to two years and overall survival for up to four years after randomization. Regular assessments will include clinical evaluations and safety monitoring to observe the effects and tolerability of the treatments during the trial.

Researchers are evaluating the safety, tolerability, and effectiveness of acalabrutinib combined with rituximab in elderly andor frail patients with diffuse large B-cell lymphoma DLBCL who have not received prior treatment and are unsuitable for standard chemotherapy. This Phase II study focuses on patients aged 65 and older, aiming to find treatment options for those who cannot undergo usual frontline chemoimmunotherapy. Participants will receive oral acalabrutinib starting on Cycle 1 Day 1 for up to 28 cycles or until disease progression or other reasons for stopping. Additionally, rituximab will be given intravenously on Cycle 1 Day 15, followed by subcutaneous injections from Cycle 2 Day 1 through Cycle 8. The study involves a single treatment arm with this combination therapy. Each participant will be involved for up to 108 weeks, including up to 28 days for screening and 104 weeks for treatment and follow-up. Researchers will assess adverse events, objective response rate, progression-free survival, overall survival, and functional mobility using the Timed Up and Go test. Safety monitoring continues throughout the study, including up to 30 days after treatment ends, to evaluate treatment-emergent adverse events and long-term outcomes.