NCT07402473

EUREKA Study:Phase 2 Study to Optimize Neoadjuvant Therapy in HER2-positive Early-stage Breast Cancer

EUREKA Study: Phase 2 Study to Optimize Neoadjuvant Therapy in HER2-positive Early-stage Breast Cancer Using ctDNA and HARPS Biomarker Assay

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Rutgers, The State University of New Jersey · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

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.

Conditions

• HER2-positive Early-stage Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab	Trastuzumab is a targeted antibody therapy used to treat HER2-positive breast and stomach cancers by blocking the growth-stimulating HER2 protein
DRUG	Pertuzumab	targeted therapy, a monoclonal antibody, used with other drugs (like trastuzumab and chemotherapy) to treat HER2-positive breast cancer, blocking HER2 proteins on cancer cells to stop their growth, and used for metastatic, locally advanced, or early-stage high-risk cases before or after surgery
DRUG	Docetaxel	will be used with HARPS Negative: intravenous chemotherapy medication used to treat breast, lung, prostate, gastric, and head/neck cancers
DRUG	Carboplatin	will be used with HARPS Negative: a platinum-based chemotherapy drug used primarily to treat advanced ovarian cancer, often in combination with other agents, as well as lung, head and neck, and brain cancers

Timeline

• Start date: 2026-03-01
• Primary completion: 2027-12-31
• Completion: 2028-06-30
• First posted: 2026-02-11
• Last updated: 2026-02-11

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study