Pilot Study of Neoadjuvant Chemotherapy Combined With Immunotherapy and Multimodal Thermal Therapy for HER2-negative Breast Cancer

A Prospective, Open-label, Single-center, Pilot Study of Neoadjuvant Chemotherapy Combined With Immunotherapy and Multimodal Thermal Therapy for HER2-negative Breast Cancer

In this study, breast cancer (BC) patients eligible for inclusion will be divided into two groups according to molecular typing and subtyping, which combined immunotherapy and multimodal thermal therapy with conventional neoadjuvant chemotherapy, to explore methods of immune induction for BC, enhance the efficacy of immunotherapy, and accumulate data for subsequent stages of clinical study.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Female; HER2-negative Breast Cancer
• Intervention / Treatment: Combination product: Device: Multimodal Tumor Thermal Therapy System Drug: Camrelizumab Drug: Nab paclitaxel Drug: Carboplatin; Combination product: Device: Multimodal Tumor Thermal Therapy System Drug: Camrelizumab Drug: Nab paclitaxel Drug: Carboplatin Drug: Goserelin

Detailed Description

Local tumor destruction with non-surgical ablation (NSA, cryoablation or radiofrequency) induces inflammation and releases antigens that can activate tumor-specific immune responses.

Pre-clinically, we demonstrated that multimodal thermal therapy (MTT) as an integrated treatment modality of cryotherapy and radiofrequency heating, can effectively activate systemic and long-lasting antitumor immunity.

In this pilot study, patients with operable HER2-negative breast cancer were designed to receive a combination of MTT, immunotherapy and neoadjuvant chemotherapy. Potential favorable intra-tumoral and systemic immunologic effects were assessed with the combination, revealing the possibility for induced and synergistic anti-tumor immunity with this strategy.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhimin Shao, M.D; Phone Number: 88807 : +86-021-64175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Breast cancer institute of Fudan University Cancer Hospital
      • Contact: Zhimin Shao, M.D; Phone Number: 86-21-64175590; Email: zhimingshao@yahoo.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female，age 18-70 years.
2. Histologically confirmed invasive cancer of the breast, and patients meeting cT2-4N+M0 criteria;
3. TNBC non-immunoregulation subtype or HR+/HER2- status were measured by immunohistochemistry (IHC);
4. At least one measurable lesion according to RECIST 1.1 criteria;
5. Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
6. LVEF ≥55%;
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
8. Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug;
9. Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria:

1. Previous cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any reason;
2. Patients with New York Heart Association (NYHA) grade II or above heart disease (including grade II);
3. Patients with severe systemic infections or other serious diseases;
4. Patients with known allergy or intolerance to the study drug or its excipients;
5. Other malignant tumors in the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer;
6. Pregnant or lactating patients of childbearing age who refused to take appropriate contraceptive measures during the course of the study;
7. Participated in other trial studies within 30 days before the administration of the first dose of the study drug;
8. Endocrine system disorders;
9. Patients who were judged by the investigator to be unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triple-negative Breast Cancer with Non-immunomodulatory Subtype	Combination product: Device: Multimodal Tumor Thermal Therapy System Drug: Camrelizumab Drug: Nab paclitaxel Drug: Carboplatin; Drugs was given a few days after multimodal thermal therapy
Experimental: Hormone Receptor-positive (HR+) and HER2-negative (HER2-)	Combination product: Device: Multimodal Tumor Thermal Therapy System Drug: Camrelizumab Drug: Nab paclitaxel Drug: Carboplatin Drug: Goserelin; Drugs was given a few days after multimodal thermal therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of immune activating response	Proportion of subjects with immune response to combination therapy detected by biomarkers in peripheral blood samples; Evaluate the infiltration of immune cells in tumor areas and adjacent tissues	up to 28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CTCAE scale (V4.0)	To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V4.0)	up to 28 weeks

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): November 18, 2024
• Primary Completion (Estimated): February 7, 2025
• Study Completion (Estimated): October 7, 2026

Study Registration Dates

• First Submitted: September 29, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Hormonal; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Carboplatin; Paclitaxel; Goserelin
• Other Study ID Numbers: MTT-BC-002

Drug and device information, study documents

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