Study of High-Intensity Focused Ultrasound (HIFU) Combined With Toripalimab Plus Chemotherapy Versus Chemotherapy as Neoadjuvant Therapy for Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (NeoHunter) (NeoHunter)

A Randomized, Open-Label, Blinded Endpoint Study of High-Intensity Focused Ultrasound (HIFU) Combined With Toripalimab Plus Chemotherapy Versus Chemotherapy as Neoadjuvant Therapy for Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (NeoHunter)

The purpose of this study is to evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with toripalimab plus chemotherapy versus chemotherapy as neoadjuvant therapy for ER+/HER2- breast cancer.

Study Overview

• Status: Recruiting
• Conditions: ER+/HER2- Breast Cancer
• Intervention / Treatment: Procedure: HIFU; Drug: Toripalimab; Drug: nab-Paclitaxel (nab-P); Drug: Epirubicin (E); Drug: Cyclophosphamide (C)

Detailed Description

Study participants will be randomly allocated to either the experimental group or the control group and receive the following treatments. Experimental group: HIFU therapy followed by 8 cycles of neoadjuvant immunotherapy and chemotherapy; Control group: 8 cycles of neoadjuvant chemotherapy alone. Each cycle lasts 21 days. Subsequently, all participants will undergo surgery within 6 weeks after completion of neoadjuvant therapy.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yiding Chen; Phone Number: +86 0571 87783759; Email: ydchen@zju.edu.cn
• Study Contact Backup: Name: Shijie Wu; Email: shijiewu@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Yiding Chen; Phone Number: +86 0571 87783759; Email: ydchen@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients aged 18-75 years.
2. Invasive breast cancer without distant metastasis, including either T1c-T2 (≥ 2 cm), cN1-cN2, or T3-T4, cN0-cN2.
3. Histopathologically confirmed ER-positive/HER2-negative, PR < 20% or Ki67 ≥ 20%, Grade 3 breast cancer.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion Criteria:

1. Female patients during pregnancy or lactation.
2. Diagnosis of bilateral breast cancer, occult breast cancer, or distant metastasis confirmed by pathology.
3. Has an active autoimmune disease that has received systemic treatment in the last 2 years.
4. Has a known history of human immunodeficiency virus (HIV), hepatitis B, or known active hepatitis C virus infection.
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
6. Has a known history of invasive malignancy that required systemic treatment in the last 5 years.
7. Uncontrolled concomitant diseases include severe infection, liver disease, cardiovascular disease, kidney disease, respiratory disease, diabetes, and others requiring systemic treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIFU/Toripalimab + nab-P/Toripalimab + EC; Participants receive HIFU treatment, followed by toripalimab (Q3W) + nab-Paclitaxel (QW) for 4 cycles (12 weeks), followed by toripalimab (Q3W) + epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks). Each cycle lasts 21 days.	Procedure: HIFU; HIFU therapy is administered to the targeted breast lesion site.; Drug: Toripalimab; 240 mg, IV infusion, Q3W; Drug: nab-Paclitaxel (nab-P); 125 mg/m2, IV infusion, QW; Drug: Epirubicin (E); 90 mg/m2, IV infusion, Q3W; Drug: Cyclophosphamide (C); 600 mg/m2, IV infusion, Q3W
Active Comparator: nab-P/EC; Participants receive nab-Paclitaxel (QW) for 4 cycles (12 weeks), followed by epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks). Each cycle lasts 21 days.	Drug: nab-Paclitaxel (nab-P); 125 mg/m2, IV infusion, QW; Drug: Epirubicin (E); 90 mg/m2, IV infusion, Q3W; Drug: Cyclophosphamide (C); 600 mg/m2, IV infusion, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pathological Complete Response (tpCR) Rate: ypT0/Tis, ypN0	The tpCR rate is defined as the proportion of participants with no residual invasive cancer cells in both the breast primary tumor site (residual in situ cancer cells are permitted) and all sampled axillary lymph nodes.	Up to approximately 30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast Pathological Complete Response (bpCR) Rate: ypT0/Tis	The bpCR rate is defined as the proportion of participants with no residual invasive cancer cells in the breast primary tumor site (residual in situ cancer cells are permitted).	Up to approximately 30 weeks
Objective Response Rate (ORR)	ORR is defined as the proportion of participants with a complete or partial response.	Up to approximately 30 weeks
Event-Free Survival (EFS)	EFS is defined as the time from randomization to any of the following events: precludes surgery, local or distant recurrence, second primary malignancy, or death due to any cause.	Approximately five years
Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a study participant administered a medicinal product, temporally associated with study intervention, without presumption of causality.	Approximately three years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Yiding Chen, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 28, 2025
• First Submitted That Met QC Criteria: May 7, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Epirubicin; Cyclophosphamide; PD1; Breast Neoplasms; Toripalimab; nab-Paclitaxel; High-intensity focused ultrasound
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Cyclophosphamide; Paclitaxel; Epirubicin
• Other Study ID Numbers: 2024-0367

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No