EUREKA Study: Phase 2 Study to Optimize Neoadjuvant Therapy in HER2-positive Early-stage Breast Cancer Using ctDNA and HARPS Biomarker Assay
This is an open-label phase 2 study to evaluate the pCR rate in patients diagnosed with HER2 positive breast cancer treated on an adaptive clinical trial design. Tumors will undergo testing using a novel molecular phosphoprotein-based biomarker assay, HER2 Activation Response Predictive Signature (HARPS) to identify HARPS-positive breast cancers. To assess 3-year invasive disease-free survival (iDFS) in patients with HARPS-positive and HARPS-negative HER2-positive breast cancer. To correlate changes in ctDNA with treatment outcomes in patients with HARPS-positive and HARPS-negative HER2-positive breast cancer. To understand the changes in quality of life (QOL) measure in patients with HARPS-positive HER2-positive breast cancer treated using an adaptive neoadjuvant trial design.
⁃ Tumor size greater than 2cm or lymph node positive by imaging or clinical exam (cT2-T3 N0-2)
• Tumors must be HER2 positive either by IHC (3+) or by IHC 2+ and FISH positive.
• Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry
• Patient must have adequate tumor for HARPS testing.
• Patients must have ctDNA collection prior to treatment on trial.
• Patient must be able to do breast MRI as determined by the study
• Baseline LVEF \> 50% (Most recent within the last 5 years)
• No prior history of systemic treatment with anthracyclines-based chemotherapy.
• Adequate bone marrow function:
∙ ANC ≥ 1500/uL
‣ platelet count ≥ 100,000/uL
‣ hemoglobin ≥ 9.0 g/dL
⁃ Adequate hepatic function:
• Total bilirubin ≤ 1.5 X ULN
∙ AST (SGOT) ≤ 5 X ULN
∙ ALT (SGPT) ≤ 5 X ULN
⁃ Patients with biliary obstruction must have restored biliary flow by placement of an endoscopic common bile duct stent or a percutaneous drainage.
⁃ Adequate renal function, Creatinine \< 1.5x institutional ULN or calculated creatinine clearance ≥ 50 mL/min as estimated using the Cockcroft-Gault formula.
⁃ Ability to understand the nature of this study protocol and give written informed consent.
⁃ Willingness and ability to comply with scheduled visits and treatment plans
⁃ Prior cancers allowed if no evidence of disease in last 5 years. Prior history of ipsilateral invasive breast cancers are not allowed.