Alfenas

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor CDK46i and letrozole compared to placebo plus CDK46i and letrozole in adults with endocrine-sensitive PIK3CA-mutated hormone receptor-positive HR, HER2-negative advanced breast cancer. This phase III, randomized, double-blind study focuses on participants who have measurable disease and meet specific hormone receptor and HER2 status criteria. Participants are randomly assigned to receive either oral inavolisib once daily along with letrozole and CDK46i or placebo once daily with letrozole and CDK46i. The CDK46i is given on a schedule of either Days 1-21 or Days 1-28 of each 28-day cycle. The study includes parallel groups to compare these treatment combinations over time. During the study, participants will be monitored for progression-free survival, overall survival, response rates, duration of response, clinical benefit, and changes in pain, physical function, and global health status. Safety will be assessed by tracking adverse events and patient-reported treatment side effects using questionnaires. The study will follow participants for up to seven years, with regular evaluations to track disease status and quality of life.

Researchers are evaluating camizestrant against standard endocrine therapy for patients with ER-positive, HER2-negative early breast cancer who have an intermediate or high risk of disease recurrence. These patients must have completed locoregional therapy and at least 2 to 5 years of standard adjuvant endocrine therapy. The study is a Phase III open-label trial focused on improving outcomes for these patients over a long-term period. Participants are randomly assigned to receive either camizestrant orally or continue with the standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors exemestane, letrozole, anastrozole or tamoxifen. Treatment in each group lasts for 60 months. The study allows prior use of CDK46 inhibitors and includes a follow-up period extending up to 10 years from the last patient randomization. During the study, participants will undergo regular assessments to monitor invasive breast cancer-free survival and other outcomes such as invasive disease-free survival, distant relapse-free survival, overall survival, and safety. Researchers will also evaluate symptoms like joint pain, hot flushes, and vaginal dryness using specific scales, along with quality of life measures and pharmacokinetics. Safety monitoring continues up to 28 days after the last dose, and participants remain under observation for up to 10 years total.

Researchers are evaluating the combination of capivasertib with CDK46 inhibitors and fulvestrant in adults with hormone receptor-positive and HER2-negative locally advanced or metastatic breast cancer. This Phase IbIII study aims to determine the safe dose for the combination treatment in the initial Phase Ib part and then compare its effectiveness and safety to standard treatment in the Phase III part in participants who have not received prior endocrine therapy in the advanced setting. In the Phase Ib portion, participants receive capivasertib combined with one of the CDK46 inhibitorspalbociclib, ribociclib, or abemacicliband fulvestrant to establish recommended doses. In the Phase III part, participants are randomly assigned to receive either capivasertib plus fulvestrant with a chosen CDK46 inhibitor palbociclib or ribociclib or fulvestrant with a CDK46 inhibitor alone. Treatments are given in 28-day cycles with specific dosing schedules for each drug, including oral doses of capivasertib and CDK46 inhibitors and injections of fulvestrant. Participants undergo screening and regular monitoring throughout the study, including assessments of treatment side effects, tumor progression, and blood samples for pharmacokinetics and biomarker analysis. The primary outcomes include dose-limiting toxicities and adverse events in Phase Ib and progression-free survival in Phase III, with follow-up lasting up to several years to evaluate overall survival, response rates, physical functioning, and quality of life.