Optimize Neoadjuvant Therapy in HER2-Positive Early-Stage Breast Cancer
Start Date
3/26/2026
Completion Date
6/30/2028
Summary
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.
Detailed Description
EUREKA is a phase II study that will evaluate optimization of neoadjuvant therapy in patients with stage II-III HER2-positive breast cancer. This adaptive clinical trial will enroll patients with cT2-T3 N0-2 HER2-positive breast cancer. Tumors will undergo testing using HARPS assay to identify HARPS-positive and HARPS negative HER2-positive breast cancers. Patients with HARPS-positive HER2-positive breast cancer will be treated using an adaptive trial design to optimize neoadjuvant therapy such we are maximizing treatment efficacy while reducing risk of treatment related toxicities. Patient will be treated with dual HER2-targeted therapy (trastuzumab and pertuzumab) for 3 cycles. Treatment response will be monitored by ctDNA and MRI breast. If there is treatment response, patients will be treated with 6 cycles of trastuzumab and pertuzumab. If there is no treatment response after 6 weeks, then patients will be treated with the addition of single agent chemotherapy (docetaxel/paclitaxel/Abraxane) with trastuzumab/pertuzumab for 4 cycles followed by 2 cycles of trastuzumab and pertuzumab. Then patients will proceed with breast surgery. Patients with HARPS-negative HER2-positive breast cancer and detectable ctDNA at time of diagnosis will be treated with 4 cycles of Taxane, platinum, trastuzumab and pertuzumab, and they will be monitored with ctDNA for ctDNA clearance. Patients who have ctDNA clearance will be treated with additional 2 cycles of the same regimen and then proceed to have surgery. If patients have detectable ctDNA at 12 weeks, then neoadjuvant therapy will be escalated to add anthracycline based regimen or trastuzumab deruxtecan (T-DXD) pe treating physicians choice. The study will enroll a total of 50 patients- 25 patients with HARPS-positive HER2-positive early-stage breast cancer and 25 patients with HARPS-negative HARPS-positive early-stage breast cancer.
Eligibility Criteria
Age Range: 18 years to 90 years
Interventions
Trastuzumab
Pertuzumab
Docetaxel
Carboplatin
Conditions
Locations
RWJBarnabas Health - Trinitas Hospital and Comprehensive Cancer Center
Elizabeth, New Jersey 07202
United States
RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton
Hamilton, New Jersey 08690
United States
RWJBarnabas Health - Monmouth Medical Center
Long Branch, New Jersey 07740
United States
Rutgers Cancer Institute
New Brunswick, New Jersey 08901
United States
RWJBarnabas Health - Newark Beth Israel Medical Center
Newark, New Jersey 07112
United States
RWJBarnabas Health - Robert Wood Johnson University Hospital, Somerset
Somerville, New Jersey 08876
United States
RWJBarnabas Health - Community Medical Center
Toms River, New Jersey 08755
United States