Optimizing neoadjuvant treatment for HER2‑positive early breast cancer

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

This trial will test whether using a new biomarker called HARPS to guide pre-surgery HER2-targeted therapy (trastuzumab and pertuzumab, with chemotherapy added when needed) improves treatment response for people with HER2‑positive early breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: Rutgers, The State University of New Jersey (Academic / other)
• Drugs / interventions: chemotherapy, radiation, trastuzumab, pertuzumab
• Locations: 7 sites (Elizabeth, New Jersey and 6 other locations)
• Trial ID: NCT07402473 on ClinicalTrials.gov

What this trial studies

EUREKA is an open-label phase II adaptive neoadjuvant approach for patients with cT2–T3 N0–2 HER2‑positive breast cancer that uses a phosphoprotein assay (HARPS) to classify tumors as HARPS‑positive or HARPS‑negative. HARPS‑positive patients begin with three cycles of trastuzumab and pertuzumab and are monitored with ctDNA and breast MRI to decide whether to continue dual HER2 therapy or add a single-agent taxane for nonresponders before surgery. HARPS‑negative patients with detectable ctDNA receive a taxane/platinum plus trastuzumab and pertuzumab regimen and are followed for ctDNA clearance to guide additional cycles. Primary endpoints include pathologic complete response and three‑year invasive disease‑free survival, with correlative analyses of ctDNA dynamics and quality-of-life measures.

Who should consider this trial

Good fit: Ideal candidates are people with cT2–T3 N0–2 HER2‑positive breast cancer who have adequate tumor tissue for HARPS testing, can provide baseline ctDNA, have LVEF >50%, adequate blood and liver function, and no prior anthracycline systemic chemotherapy.

Not a fit: Patients with tumors ≤2 cm, significant cardiac dysfunction, prior anthracycline exposure, or who cannot provide required tissue or ctDNA samples are unlikely to qualify or benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could personalize pre-surgery HER2 therapy to increase effective responses while reducing unnecessary chemotherapy and its side effects.

How similar studies have performed: Dual HER2-targeted neoadjuvant regimens have raised pCR rates in prior trials and ctDNA-guided strategies are promising, but the HARPS phosphoprotein biomarker itself is novel and not yet validated in large randomized studies.

Eligibility criteria

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

Where this trial is running

Elizabeth, New Jersey and 6 other locations

• RWJBarnabas Health - Trinitas Hospital and Comprehensive Cancer Center — Elizabeth, New Jersey, United States (Recruiting)
• RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton — Hamilton, New Jersey, United States (Recruiting)
• RWJBarnabas Health - Monmouth Medical Center — Long Branch, New Jersey, United States (Recruiting)
• Rutgers Cancer Institute — New Brunswick, New Jersey, United States (Recruiting)
• RWJBarnabas Health - Newark Beth Israel Medical Center — Newark, New Jersey, United States (Recruiting)
• RWJBarnabas Health - Robert Wood Johnson University Hospital, Somerset — Somerville, New Jersey, United States (Recruiting)
• RWJBarnabas Health - Community Medical Center — Toms River, New Jersey, United States (Recruiting)

Study contacts

• Study coordinator: Mridula A George

Conditions HER2-positive Early-stage Breast Cancer