Optimize Neoadjuvant Therapy in HER2-Positive Early-Stage Breast Cancer (EUREKA)

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.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Early-stage Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel; Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mridula A George; Phone Number: 732-235-9692; Email: mridula@cinj.rutgers.edu

Study Locations

• United States
  • New Jersey
    • Elizabeth, New Jersey, United States, 07202
      • Recruiting
      • RWJBarnabas Health - Trinitas Hospital and Comprehensive Cancer Center
      • Contact: Mridula George, MD; Phone Number: 7322359692; Email: mridula@.rutgers.edu
    • Hamilton, New Jersey, United States, 08690
      • Recruiting
      • RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton
      • Contact: Mridula George, MD; Phone Number: 7322359692; Email: mridula@.rutgers.edu
    • Long Branch, New Jersey, United States, 07740
      • Recruiting
      • RWJBarnabas Health - Monmouth Medical Center
      • Contact: Mridula George, MD; Phone Number: 732-235-9692; Email: mridula@rutgers.edu
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute
      • Contact: Mridula A George, MD; Phone Number: 732-235-9081; Email: mridula@rutgers.edu
    • Newark, New Jersey, United States, 07112
      • Recruiting
      • RWJBarnabas Health - Newark Beth Israel Medical Center
      • Contact: Mridula George, MD; Phone Number: 7322359692; Email: mridula@.rutgers.edu
    • Somerville, New Jersey, United States, 08876
      • Recruiting
      • RWJBarnabas Health - Robert Wood Johnson University Hospital, Somerset
      • Contact: Mridula George, MD; Phone Number: 7322359692; Email: mridula@.rutgers.edu
    • Toms River, New Jersey, United States, 08755
      • Recruiting
      • RWJBarnabas Health - Community Medical Center
      • Contact: Mridula George, MD; Phone Number: 732-235-9692; Email: mridula@rutgers.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inclusion Criteria

  1. Tumor size greater than 2cm or lymph node positive by imaging or clinical exam (cT2-T3 N0-2)
  2. Tumors must be HER2 positive either by IHC (3+) or by IHC 2+ and FISH positive.
  3. Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry
  4. Patient must have adequate tumor for HARPS testing.
  5. Patients must have ctDNA collection prior to treatment on trial.
  6. Patient must be able to do breast MRI as determined by the study
  7. Baseline LVEF > 50% (Most recent within the last 5 years)
  8. No prior history of systemic treatment with anthracyclines-based chemotherapy.

  9. Adequate bone marrow function:

     • ANC ≥ 1500/uL
     • platelet count ≥ 100,000/uL
     • hemoglobin ≥ 9.0 g/dL

  10. Adequate hepatic function:

      • Total bilirubin ≤ 1.5 X ULN
      • AST (SGOT) ≤ 5 X ULN
      • ALT (SGPT) ≤ 5 X ULN
  11. Patients with biliary obstruction must have restored biliary flow by placement of an endoscopic common bile duct stent or a percutaneous drainage.
  12. Adequate renal function, Creatinine < 1.5x institutional ULN or calculated creatinine clearance ≥ 50 mL/min as estimated using the Cockcroft-Gault formula.
  13. Ability to understand the nature of this study protocol and give written informed consent.
  14. Willingness and ability to comply with scheduled visits and treatment plans
  15. Prior cancers allowed if no evidence of disease in last 5 years. Prior history of ipsilateral invasive breast cancers are not allowed.

Exclusion Criteria:

1. Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer. Exception: patients can start upto 1 cycle of HP prior to starting treatment on study.
2. cT4 and/or cN3 tumors
3. Evidence of metastatic disease by routine clinical assessment
4. Bilateral breast cancer
5. History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma
6. Left ventricular ejection fraction (LVEF) below 50% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO)
7. No active liver disease.
8. Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
9. Pre-existing sensory neuropathy > grade 1.
10. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
11. Serious non-healing wound, ulcer, or bone fracture
12. Patient with uncontrolled and/ or active infection with HIV, Hepatitis B or Hepatitis C.
13. Patient who has a history of allergy or hypersensitivity to any of the study drugs.
14. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HARPS POSITIVE COHORT; Arm A HARPS POSITIVE COHORT PART A: Patients with HARPS positive HER2 positive breast cancer will be treated with trastuzumab and pertuzumab for three cycles. PART B: Patients who have adequate treatment response after 3 cycles, continue trastuzumab and pertuzumab every 3 weeks for a minimum of 8 cycles in the neoadjuvant setting ARM B: HARPS-NEGATIVE COHORT Patients with HARPS negative tumors must have baseline detectable ctDNA. If patients do not have detectable ctDNA, they will be taken off study. These patients will be replaced.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) Assessed by CTCAE v5.0	The HARPS assay will be used to identify patients with HARPS positive and HARPS-negative HER2-positive breast cancer. Patients with Stage I-III who meet the specified eligibility criteria would be enrolled in the adaptive clinical trial. The study aims to understand whether the HARPS assay can help optimize the treatment regimen for patients diagnosed with HER2 positive breast cancer. The study will evaluate the pCR rates in patients treated with the adaptive trial regimen. The hypothesis of the study is that the adaptive treatment regimen will help improve pCR rates in patients diagnosed HER2-positive breast cancer based on the HARPS status of the tumor.	up to 36 months

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Trastuzumab; Carboplatin; pertuzumab
• Other Study ID Numbers: 042507; Pro2025002581 (Other Identifier: Rutgers Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes