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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Trastuzumab is a targeted antibody therapy used to treat HER2-positive breast and stomach cancers by blocking the growth-stimulating HER2 protein
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
will be used with HARPS Negative: intravenous chemotherapy medication used to treat breast, lung, prostate, gastric, and head/neck cancers
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
RWJBarnabas Health - Trinitas Hospital and Comprehensive Cancer Center
Elizabeth, New Jersey, United States
RECRUITINGRWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton
Hamilton, New Jersey, United States
RECRUITINGRWJBarnabas Health - Monmouth Medical Center
Long Branch, New Jersey, United States
RECRUITINGRutgers Cancer Institute
New Brunswick, New Jersey, United States
RECRUITINGRWJBarnabas Health - Newark Beth Israel Medical Center
Newark, New Jersey, United States
RECRUITINGRWJBarnabas Health - Robert Wood Johnson University Hospital, Somerset
Somerville, New Jersey, United States
RECRUITINGRWJBarnabas Health - Community Medical Center
Toms River, New Jersey, United States
RECRUITINGIncidence 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.
Time frame: up to 36 months
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