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

NCT07565324 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 202509103MINB
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HER-2 Positive Breast Cancer

Keywords

HER2; Breast cancer; Lipodox; Cyclophosphamide; Trastuzumab; Pertuzumab

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission rate (pCR)

  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 Outcomes (4)

• Number of participants with Lipodox-containing regimen-related adverse events of cardiac function as assessed by CTCAE v4.0

  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]

  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.

  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

  After completion of neoadjuvant chemotherapy regimens.

Study Arms (1)

Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for HER2-positive Breast Cancer Patients

EXPERIMENTAL

Drug: Lipo-Dox®; Drug: Cyclophosphamide; Drug: Trastuzumab (Herceptin); Drug: Pertuzumab

Interventions

Lipo-Dox® DRUG

Lipo-Dox®: 37.5 mg/m² on D1; every 21 days is one cycle, for a total of 4 cycles.

Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for HER2-positive Breast Cancer Patients

Cyclophosphamide DRUG

Cyclophosphamide 600 mg/m² on D1, ; every 21 days is one cycle, for a total of 4 cycles.

Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for HER2-positive Breast Cancer Patients

Trastuzumab (Herceptin) DRUG

Trastuzumab 6 mg/kg on D2; every 21 days is one cycle, for a total of 4 cycles.

Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for HER2-positive Breast Cancer Patients

Pertuzumab DRUG

Pertuzumab 420 mg on D2; every 21 days is one cycle, for a total of 4 cycles.

Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for HER2-positive Breast Cancer Patients

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: HER2-positive Primary Invasive Breast Cancer
• Patients must meet the following criteria for study entry:
• Histologically confirmed invasive breast carcinoma
• HER2-positive breast carcinoma
• 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.
• 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.
• Clinical stage at presentation: T1-4, N0-3, M0 (T1N0M0 tumors will not be eligible)
• Patients must be willing to receive preoperative systemic chemotherapy with taxanes and HER-2-targeting treatment for at least 4 to 6 cycles.
• Systemic therapy must consist of at least 4 to 6 cycles of chemotherapy with taxanes plus trastuzumab (TH) or
• Systemic therapy must consist of at least 4 to 6 cycles of chemotherapy with taxanes plus trastuzumab and pertuzumab (THP).
• 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.
• Age ≥ 20 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Adequate organ function during screening, included:

You may not qualify if:

• Stage IV (metastatic) breast cancer.
• History of any prior (ipsilateral- or contralateral) breast cancer except lobular carcinoma in situ.
• 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.
• 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).
• Current NCI common terminology criteria for adverse events (CTCAE) (Version 4.0): Grade ≥ 2 peripheral neuropathy.
• 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.
• Prior treatment with anthracycline or Lipo-Dox®
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers).
• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• TTY Biopharm: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (4)

• Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9. Epub 2011 Dec 6.

  PMID: 22153890 BACKGROUND

• van der Voort A, van Ramshorst MS, van Werkhoven ED, Mandjes IA, Kemper I, Vulink AJ, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS. Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial. JAMA Oncol. 2021 Jul 1;7(7):978-984. doi: 10.1001/jamaoncol.2021.1371.

  PMID: 34014249 BACKGROUND

• Tseng LM, Chen FM, Chen ST, Cheng FT, Chao TY, Dai MS, Kao WY, Yeh MH, Chen DR, Liu LC, Wang HC, Chang HT, Wang BW, Yu JC, Chen SC, Liao GS, Hou MF. Comparison of the Efficacy, Safety, and Quality of Life of Pegylated Liposomal Doxorubicin-Cyclophosphamide versus Epirubicin-Cyclophosphamide in Patients with Early-Stage HER2-Negative Breast Cancer: A Prospective, Randomized, Multicenter, Phase II Study. Oncol Res Treat. 2024;47(10):484-495. doi: 10.1159/000540369. Epub 2024 Jul 19.

  PMID: 39033747 BACKGROUND

• Lin PH, Tsai LW, Lo C, Kuo SH, Ni CC, Yu CH, Huang CS. ctDNA Detected after Neoadjuvant Therapy for HER2-Positive Breast Cancer Is Associated with Inferior Outcomes and May Inform Adjuvant Therapy. Cancer Res Commun. 2026 Jan 1;6(1):105-114. doi: 10.1158/2767-9764.CRC-24-0234.

  PMID: 41543393 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Sung-Hsin Kuo, M.D.,Ph.D.

CONTACT

+886-972651671; shkuo101@ntu.edu.tw

Chiun-Sheng Huang, M.D.,Ph.D.

CONTACT

huangcs@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2026
• First Posted: May 4, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2032
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

TW (1)