Phase II Study Evaluating Treatment Effectiveness by Monitoring Minimal Residual Disease with ctDNA in HR-positiveHER2-negative Early Breast Cancer

What this Trial Is About

Researchers are studying treatments for patients with hormone receptor-positive HR-positive and HER2-negative early-stage breast cancer who are at higher risk of relapse after surgery. This phase II, open-label study focuses on using a biomarker called circulating tumor DNA ctDNA to monitor minimal residual disease. The goal is to identify patients at molecular relapse and evaluate whether treatment at this stage can improve outcomes. The study involves multiple centers and is designed to test different treatment options based on ctDNA results. The study has three phases pre-screening, molecular follow-up ctDNA surveillance, and treatment. After giving consent, about 976 eligible patients will enter the ctDNA surveillance phase where tumor tissue and blood samples are collected to create a personalized mutation panel. Blood samples will be analyzed every three months during the first year and every six months thereafter to detect ctDNA. When ctDNA positivity is confirmed, up to 40 patients will be assigned sequentially to one of four treatment arms continuing standard endocrine therapy ET, giredestrant alone, giredestrant with abemaciclib, or giredestrant with inavolisib. Treatments are taken orally in cycles lasting 28 days and may continue up to five years or until disease recurrence or unacceptable side effects. Male and premenopausal participants receive additional hormone therapy LHRH agonist as needed. Participants will undergo regular blood sample collections during surveillance and treatment to monitor ctDNA levels and correlate changes with treatment response. Safety and side effects will be tracked throughout the treatment phase, which can last up to five years. After stopping treatment, patients enter a follow-up period where survival and new cancer therapies are recorded every three months. The primary outcome is measuring a decrease or clearance of ctDNA three months after starting treatment. Secondary outcomes include various ctDNA changes over time and treatment-related adverse events. Additional treatment arms may be added based on ongoing results.

A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population