This phase II trial tests whether a molecular biomarker test (HER2 activation response predictive signature [HARPS]) in combination with circulating tumor deoxyribonucleic acid (DNA) (ctDNA) monitoring can be used to adapt and optimize treatment prior to surgery (neoadjuvant) in patients with early-stage breast cancer that is HER2-positive. HER2-positive breast cancer is a type of breast cancer that grows more quickly and is driven by extra copies of the HER2 gene. Most patients with stage II or III HER2-positive breast cancer are treated before surgery with a combination of chemotherapy drugs (docetaxel, paclitaxel, carboplatin, doxorubicin, and/or cyclophosphamide) and HER2-targeted medications. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell’s DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s DNA and may kill cancer cells. It may also lower the body’s immune response. Treatments that target HER2, such as trastuzumab, pertuzumab, and hyaluronidase-zzxf/pertuzumab/trastuzumab (Phesgo), have greatly improved outcomes for patients with this disease. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to HER2 receptors. When pertuzumab or trastuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that these medications will have a greater effect. Hyaluronidase also allows pertuzumab and trastuzumab to be given by injection under the skin and shortens their administration time compared to pertuzumab or trastuzumab alone. Although this approach with combination chemotherapy and HER2-targeted therapy is effective, chemotherapy can cause significant side effects that may affect quality of life or lead to long-term complications. Recent research suggests that some patients may respond very well to HER2-targeted therapy alone, without needing chemotherapy. The HARPS biomarker assay is a new test designed to identify which patients may safely reduce or avoid chemotherapy while still achieving a good response. This study may help determine if using the HARPS test can help doctors personalize treatment for patients with HER2-positive breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07402473.
Locations matching your search criteria
United States
New Jersey
Elizabeth
Trinitas Hospital and Comprehensive Cancer Center - Williamson Street CampusStatus: Approved
Contact: Trishala Meghal
Phone: 800-994-8000
Hamilton
The Cancer Institute of New Jersey HamiltonStatus: Approved
Contact: Meera Yogarajah
Phone: 609-631-6960
Jersey City
Jersey City Medical CenterStatus: Approved
Contact: Allan Louie Espino Cruz
Phone: 201-915-2000
Livingston
Saint Barnabas Medical CenterStatus: Approved
Contact: George Raptis
Phone: 972-322-5200
Long Branch
Monmouth Medical CenterStatus: Approved
Contact: Patrick Lee
Phone: 732-222-1711
New Brunswick
Rutgers Cancer Institute of New JerseyStatus: Approved
Contact: Mridula Annette George
Phone: 732-235-9692
Newark
Newark Beth Israel Medical CenterStatus: Approved
Contact: Sari Jacoby
Phone: 973-926-7230
Somerville
Robert Wood Johnson University Hospital SomersetStatus: Approved
Contact: Kathleen C. Toomey
Phone: 908-972-8702
Toms River
Community Medical CenterStatus: Approved
Contact: Seth D. Cohen
Phone: 732-505-1500
PRIMARY OBJECTIVE:
I. To evaluate the rate of pathologic complete response (pCR) using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) as assessed by the local pathologist at the time of definitive surgery in subjects with HARPS-positive and HARPS-negative HER2-positive breast cancer treated using an adaptive neoadjuvant trial design.
SECONDARY OBJECTIVES:
I. To assess 3-year invasive disease-free survival (iDFS) in patients with HARPS-positive and HARPS-negative HER2-positive breast cancer.
II. To correlate changes in ctDNA with treatment outcomes in patients with HARPS-positive and HARPS-negative HER2-positive breast cancer.
III. 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.
EXPLORATORY OBJECTIVE:
I. To understand resistance mechanisms in patients who have residual disease post-neoadjuvant therapy by analyzing the primary and residual tumor. (HARPS-positive and HARPS-negative)
OUTLINE: Patients are assigned to 1 of 2 cohorts based on HARPS status.
HARPS POSITIVE COHORT:
PART A: Patients receive trastuzumab IV and pertuzumab IV or hyaluronidase-zzxf/pertuzumab/trastuzumab (Phesgo) SC on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo MRI and blood sample-based ctDNA measurement and proceed to Part B.
PART B:
NEOADJUVANT THERAPY: Patients with adequate treatment response after 3 cycles continue receiving trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each cycle. Cycles repeat every 21 days for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Patients with progression or without adequate treatment response after 3 cycles receive docetaxel IV on day 1 or paclitaxel IV on days 1, 8, and 15 of each cycle in combination with trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may instead receive docetaxel IV on day 1 or paclitaxel IV on days 1, 8, and 15 and carboplatin IV on day 1 in combination with trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each 21-day cycle for 4 cycles in the absence of disease progression or unacceptable toxicity, at the discretion of the investigator. After 4 cycles of combination therapy, patients receive trastuzumab IV and pertuzumab IV or Phesgo SC alone on day 1 of each 21-day cycle until the time of surgery (for up to 8 cycles of neoadjuvant therapy). After 8 cycles of neoadjuvant therapy, patients proceed to breast surgery.
ADJUVANT THERAPY: Following surgery, patients receive treatment at the discretion of the treating physician. Patients who demonstrate pathologic complete response may receive trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Patients without pathologic complete response may receive trastuzumab emtansine (T-DM1) IV on day 1 of each cycle. Cycles repeat every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
HARPS NEGATIVE COHORT:
PART A: Patients receive docetaxel IV on day 1 or paclitaxel IV on days 1, 8, and 15 and carboplatin IV on day 1 in combination with trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo blood sample-based ctDNA measurement and proceed to Part B.
PART B:
NEOADJUVANT THERAPY: Patients with adequate treatment response after 4 cycles continue receiving docetaxel IV on day 1 or paclitaxel IV on days 1, 8, and 15 and carboplatin IV on day 1 in combination with trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each cycle. Cycles repeat every 21 days for up to 2 additional cycles in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV and pertuzumab IV or Phesgo SC alone on day 1 of each cycle. Cycles repeat every 21 days until the time of surgery in the absence of disease progression or unacceptable toxicity. Patients without adequate treatment response after 4 cycles receive either doxorubicin IV and cyclophosphamide IV on day 1 of each cycle or trastuzumab deruxtecan (T-DXD) IV on day 1 of each cycle, per the treating physician's choice. Cycles of doxorubicin and cyclophosphamide repeat every 14 days and cycles of T-DXD repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles of neoadjuvant therapy, patients proceed to breast surgery.
ADJUVANT THERAPY: Following surgery, patients receive treatment at the discretion of the treating physician. Patients who demonstrate pathologic complete response may receive trastuzumab IV and pertuzumab IV or Phesgo SC on day 1 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Patients without pathologic complete response may receive T-DM1 (or T-DXD, per treating physician's discretion) IV on day 1 of each cycle. Cycles repeat every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
All patients undergo collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up in months 3, 6, 9, 12, 18, 24, and 36.
Lead OrganizationRutgers Cancer Institute of New Jersey
Principal InvestigatorMridula Annette George
