Phase II Study of Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for Patients With HER2-positive Early Breast Cancer (UC HER Trial) (UC HER)

April 27, 2026 updated by: National Taiwan University Hospital

Phase II Study of Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for Patients With HER2-positive Early Breast Cancer

Although neoadjuvant dual anti-HER2-targeted therapy, pertuzumab and trastuzumab, combined with taxanes increased the pCR rate for patients with early-stage HER2-positive breast cancer when compared with single blockade combined with chemotherapy, certain patients did not achieve pCR after receiving dual blockade or single blockade targeting HER2 combined with taxanes.

Based on the cardiac safety and promising ORR rate of the regimens consisting of PLD and cyclophosphamide and trastuzumab in treating patients with HER2-positive breast cancer in the neoadjuvant or metastatic setting, the investigators hypothesized that dual blockades targeting HER2, trastuzumab and pertuzumab, combined with PLD and cyclophosphamide, will not only increase the pCR rate but also cause less cardiotoxicity for participants with residual cancer via core biopsy or non-clinical CR after receiving taxanes plus trastuzumab and pertuzumab or taxanes plus trastuzumab. The investigators also showed that ctDNA served as the surrogate prognostic marker for participants with HER2-positive EBC who received neoadjuvant trastuzumab-based regimens.

In this study, the investigators will explore whether the combination of PLD (Lipo-Dox®, Liposomal Doxorubicin Injection), cyclophosphamide, trastuzumab, and pertuzumab can increase the pCR rate of participants with HER2-positive EBC if they have residual cancers (core biopsy, non-clinical CR, or positive ctDNA) after receiving a trastuzumab and taxanes-based NAT regimen. In addition, the cardiac safety, adverse effects, and clearance of ctDNA will be explored for these patients. The investigators further assess the feasibility of VAB (before operation) in these participants who achieved negative ctDNA after receiving Lipo-Dox® plus cyclophosphamide, trastuzumab, and pertuzumab.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Diagnosis: HER2-positive Primary Invasive Breast Cancer

Patients must meet the following criteria for study entry:

  1. Histologically confirmed invasive breast carcinoma

  2. HER2-positive breast carcinoma

    1. HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by fluorescence in situ hybridization (FISH) prospectively confirmed by a pathology laboratory before study enrollment.
    2. FISH positivity is defined as a ratio of ≥ 2.0 for the number of HER2 gene copies to the number of signals for chromosome 17 copies.
  3. Clinical stage at presentation: T1-4, N0-3, M0 (T1N0M0 tumors will not be eligible)

  4. Patients must be willing to receive preoperative systemic chemotherapy with taxanes and HER-2-targeting treatment for at least 4 to 6 cycles.

    1. Systemic therapy must consist of at least 4 to 6 cycles of chemotherapy with taxanes plus trastuzumab (TH) or
    2. Systemic therapy must consist of at least 4 to 6 cycles of chemotherapy with taxanes plus trastuzumab and pertuzumab (THP).
    3. After completion of 4 to 6 cycles of TH or THP, if the following clinical features and pathological characteristics are eligible for Lipo-Dox® and cyclophosphamide plus trastuzumab and pertuzumab:

    c.1 Core biopsy showed the residual invasive breast cancer. c.2 Breast echo or other imaging studies disclosed no complete remission. c.3 Complete remission of core biopsy or breast echo or other imaging studies, but positive for ctDNA.

  5. Age ≥ 20 years.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

  7. Adequate organ function during screening, included:

    1. Absolute neutrophil count ≥ 1,200 cells/mm3
    2. Platelet count ≥ 100,000 cells/ mm3
    3. Hemoglobin ≥ 9.0 g/dL;
    4. Serum creatinine < 1.5 × upper limit of normal (ULN)
    5. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 ×ULN
    6. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 ×ULN
    7. Serum total bilirubin (TBILI) ≤ 1.0 ×ULN (within normal limits)
    8. Serum alkaline phosphatase (ALK) ≤ 1.5 ×ULN
  8. Screening LVEF ≥ 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) before receiving neoadjuvant chemotherapy with 4 to 6 courses of TH or THP and no decrease in LVEF by more than 10% absolute points from the pre-chemotherapy LVEF after 4 to 6 courses of TH or THP.
  9. For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drug.
  10. Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is required: this includes HB surface antigen (HBsAg) and/or total HB core antibody (anti-HBc) in addition to HCV antibody testing. If positive for HBsAg or positive for Anti-HBc, DNA testing for HBV will be performed. If active HBV infection is ruled out, the patient may be eligible. The most recent serologic testing must have occurred within 3 months prior to initiation of neoadjuvant therapy. If such testing has not been done, it must be performed during screening.
  11. They should receive examination of HBV DNA to document no active HBV activation (if HBeAg-positive, or HBeAg-negative but abnormal liver function accompanied by ALT ≥ 2 normal limits during the half a year and HBV DNA > 2000 IU/ml: indication of HBV activation). If test of HBsAg is positive and inactive, and they should receive prophylactic anti-HBV drugs during the enrollment period of this clinical trial.

Exclusion Criteria:

  1. Stage IV (metastatic) breast cancer.
  2. History of any prior (ipsilateral- or contralateral) breast cancer except lobular carcinoma in situ.
  3. History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ (CIS) of the cervix, non-melanoma skin carcinoma, stage I uterine cancer, or other non-breast malignancies with an outcome similar to those mentioned above.
  4. Patients for whom radiotherapy would be recommended for breast cancer treatment, but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).
  5. Current NCI common terminology criteria for adverse events (CTCAE) (Version 4.0): Grade ≥ 2 peripheral neuropathy.

  6. Cardiopulmonary dysfunction as defined by any of the following:

    History of NCI CTCAE (Version 4.0): Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II.

  7. Prior treatment with anthracycline or Lipo-Dox®
  8. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers).

  9. For female patients, current pregnancy and/or lactation. 10. Any known active liver disease, for example, due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis.

    • Patients who have positive HBV or HCV serologies without known active disease must meet the eligibility criteria for liver function on at least two consecutive occasions, separated by at least 1 week, within the 30 days-screening period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for HER2-positive Breast Cancer Patients
Drug: Lipo-Dox®
Lipo-Dox®: 37.5 mg/m² on D1; every 21 days is one cycle, for a total of 4 cycles.
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m² on D1, ; every 21 days is one cycle, for a total of 4 cycles.
Drug: Trastuzumab (Herceptin)
Trastuzumab 6 mg/kg on D2; every 21 days is one cycle, for a total of 4 cycles.
Drug: Pertuzumab
Pertuzumab 420 mg on D2; every 21 days is one cycle, for a total of 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete remission rate (pCR)
Time Frame: From enrollment to the end of operation.
Assessment of pathological specimens to determine when no cancer cells are detected in tissue samples (breast and lymph nodes) removed during surgery following preoperative treatment, such as chemotherapy.
From enrollment to the end of operation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Lipodox-containing regimen-related adverse events of cardiac function as assessed by CTCAE v4.0
Time Frame: From enrollment, before and after completion of Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab, and 12 months after operation.
Cardiac echo to assess the left ventricle ejection fractions before and after completion of Lipo-Dox®-containing regimen
From enrollment, before and after completion of Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab, and 12 months after operation.
Clearance rate of circulating tumor DNA [ctDNA]
Time Frame: From enrollment, completion of TH or THP regimens, completion of Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab, and at the end of operation.
Circulating tumor DNA (ctDNA) clearance refers to the transition from a detectable level of tumor-specific mutations in the bloodstream to undetectable levels following neoadjuvant treatment, including TH or THP regimen, or Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab.
From enrollment, completion of TH or THP regimens, completion of Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab, and at the end of operation.
Number of participants with treatment with Lipo-Dox®-containing regimen-related adverse events as assessed by CTCAE v4.0.
Time Frame: From starting a Lipo-Dox®-containing regimen to the end of treatment at 4 weeks.
Adverse events of Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab.
From starting a Lipo-Dox®-containing regimen to the end of treatment at 4 weeks.
Percentage of patients with complete removal of lesion via vacuum-assisted biopsy
Time Frame: After completion of neoadjuvant chemotherapy regimens.
Comparison of the percentage of patients with a lack of pathology at the surgery between vacuum-assisted biopsy and surgical operation (ctDNAs are negative after completion of neoadjuvant chemotherapy).
After completion of neoadjuvant chemotherapy regimens.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Collaborators

TTY Biopharm

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 30, 2026

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2032

Study Registration Dates

First Submitted

April 19, 2026

First Submitted That Met QC Criteria

April 27, 2026

First Posted (Actual)

May 4, 2026

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202509103MINB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

It is not yet known if there will be a plan to make IPD available.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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